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Sample records for adult neurogenic niches

  1. Exosomes as Novel Regulators of Adult Neurogenic Niches.

    PubMed

    Bátiz, Luis Federico; Castro, Maite A; Burgos, Patricia V; Velásquez, Zahady D; Muñoz, Rosa I; Lafourcade, Carlos A; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2015-01-01

    Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as "neurogenic niche". Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles

  2. Exosomes as Novel Regulators of Adult Neurogenic Niches

    PubMed Central

    Bátiz, Luis Federico; Castro, Maite A.; Burgos, Patricia V.; Velásquez, Zahady D.; Muñoz, Rosa I.; Lafourcade, Carlos A.; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2016-01-01

    Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as “neurogenic niche”. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their

  3. Immunological regulation of neurogenic niches in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Gutierrez-Fernandez, Fernando; Lopez-Virgen, Veronica; Collas-Aguilar, Jorge; Quinones-Hinojosa, Alfredo; Garcia-Verdugo, Jose M.

    2012-01-01

    In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular (SVZ) and subgranular (SGZ) zones are the main neurogenic regions in adult brain. Therein, it resides a subpopulation of astrocytes that act as neural stem cells. Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of neural stem cells. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor-alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of neural stem cells and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult neural stem cells under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells. PMID:22986164

  4. Influences of prenatal and postnatal stress on adult hippocampal neurogenesis: the double neurogenic niche hypothesis.

    PubMed

    Ortega-Martínez, Sylvia

    2015-03-15

    Adult hippocampal neurogenesis (AHN) is involved in learning, memory, and stress, and plays a significant role in neurodegenerative and psychiatric disorders. As an age-dependent process, AHN is largely influenced by changes that occur during the pre- and postnatal stages of brain development, and constitutes an important field of research. This review examines the current knowledge regarding the regulators of AHN and the influence of prenatal and postnatal stress on later AHN. In addition, a hypothesis is presented suggesting that each kind of stress influences a specific neurogenic pool, developmental or postnatal, that later becomes a precursor with important repercussions for AHN. This hypothesis is referred to as "the double neurogenic niche hypothesis." Discovering what receptors, transcription factors, or genes are specifically activated by different stressors is proposed as an essential line of future research in the field. Such knowledge shall constitute an important starting point toward the goal of modifying AHN in neurodegenerative or psychiatric diseases.

  5. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  6. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche.

    PubMed

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V; Sun, Bin; Dizon, Maria L V; Szele, Francis G

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  7. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    PubMed Central

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V.; Sun, Bin; Dizon, Maria L. V.; Szele, Francis G.

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  8. The Nuclear Receptor TLX Is Required for Gliomagenesis within the Adult Neurogenic Niche

    PubMed Central

    Zou, Yuhua; Niu, Wenze; Qin, Song; Downes, Michael; Burns, Dennis K.

    2012-01-01

    Neural stem cells (NSCs) continually generate functional neurons in the adult brain. Due to their ability to proliferate, deregulated NSCs or their progenitors have been proposed as the cells of origin for a number of primary central nervous system neoplasms, including infiltrating gliomas. The orphan nuclear receptor TLX is required for proliferation of adult NSCs, and its upregulation promotes brain tumor formation. However, it is unknown whether TLX is required for gliomagenesis. We examined the genetic interactions between TLX and several tumor suppressors, as well as the role of TLX-dependent NSCs during gliomagenesis, using mouse models. Here, we show that TLX is essential for the proliferation of adult NSCs with a single deletion of p21, p53, or Pten or combined deletion of Pten and p53. While brain tumors still form in Tlx mutant mice, these tumors are less infiltrative and rarely associate with the adult neurogenic niches, suggesting a non-stem-cell origin. Taken together, these results indicate a critical role for TLX in NSC-dependent gliomagenesis and implicate TLX as a therapeutic target to inhibit the development of NSC-derived brain tumors. PMID:23028043

  9. Premature aging of the hippocampal neurogenic niche in adult Bmal1-deficient mice.

    PubMed

    Ali, Amira A H; Schwarz-Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; von Gall, Charlotte

    2015-06-01

    Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1(-/-)) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1(-/-) mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1(-/-) mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70 kDa and expression of the cell cycle inhibitor p21(Waf1/CIP1) were increased in adult Bmal1(-/-) mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.

  10. Molecular targets of chromatin repressive mark H3K9me3 in primate progenitor cells within adult neurogenic niches

    PubMed Central

    Foret, Michael R.; Sandstrom, Richard S.; Rhodes, Christopher T.; Wang, Yufeng; Berger, Mitchel S.; Lin, Chin-Hsing Annie

    2014-01-01

    Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche- the subventricular zone (SVZ) on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche. PMID:25126093

  11. Layer I as a putative neurogenic niche in young adult guinea pig cerebrum.

    PubMed

    Xiong, Kun; Cai, Yan; Zhang, Xue-Mei; Huang, Ju-Fang; Liu, Zhong-Yu; Fu, Guang-Ming; Feng, Jia-Chun; Clough, Richard W; Patrylo, Peter R; Luo, Xue-Gang; Hu, Chun-Hong; Yan, Xiao-Xin

    2010-10-01

    A considerable number of cells expressing typical immature neuronal markers including doublecortin (DCX+) are present around layer II in the cerebral cortex of young and adult guinea pigs and other larger mammals, and their origin and biological implication await further characterization. We show here in young adult guinea pigs that these DCX+ cells are accompanied by in situ cell division around the superficial cortical layers mostly in layer I, but they co-express proliferating cell nuclear antigen (PCNA) and an early neuronal fate determining factor, PAX6. A small number of these DCX+ cells also colocalize with BrdU following administration of this mitotic indicator. Cranial X-ray irradiation causes a decline of DCX+ cells around layer II, and novel environmental exploration induces c-Fos expression among these cells in several neocortical areas. Together, these data are compatible with a notion that DCX+ cortical neurons around layer II might derive from proliferable neuronal precursors around layer I in young adult guinea pig cerebrum, and that these cells might be modulated by experience under physiological conditions.

  12. Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche.

    PubMed

    López-Juárez, Alejandra; Remaud, Sylvie; Hassani, Zahra; Jolivet, Pascale; Pierre Simons, Jacqueline; Sontag, Thomas; Yoshikawa, Kazuaki; Price, Jack; Morvan-Dubois, Ghislaine; Demeneix, Barbara A

    2012-05-01

    The subventricular zone (SVZ) neural stem cell niche contains mixed populations of stem cells, transit-amplifying cells, and migrating neuroblasts. Deciphering how endogenous signals, such as hormones, affect the balance between these cell types is essential for understanding the physiology of niche plasticity and homeostasis. We show that Thyroid Hormone (T(3)) and its receptor, TRα1, are directly involved in maintaining this balance. TRα1 is expressed in amplifying and migrating cells. In vivo gain- and loss-of-function experiments demonstrate first, that T(3)/TRα1 directly repress Sox2 expression, and second, that TRα1 overexpression in the niche favors the appearance of DCX+ migrating neuroblasts. Lack of TRα increases numbers of SOX2+ cells in the SVZ. Hypothyroidism increases proportions of cells in interphase. Thus, in the adult SVZ, T(3)/TRα1 together favor neural stem cell commitment and progression toward a migrating neuroblast phenotype; this transition correlates with T(3)/TRα1-dependent transcriptional repression of Sox2.

  13. Epigenetic regulation of stemness maintenance in the neurogenic niches

    PubMed Central

    Montalbán-Loro, Raquel; Domingo-Muelas, Ana; Bizy, Alexandra; Ferrón, Sacri R

    2015-01-01

    In the adult mouse brain, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are two zones that contain neural stem cells (NSCs) with the capacity to give rise to neurons and glia during the entire life of the animal. Spatial and temporal regulation of gene expression in the NSCs population is established and maintained by the coordinated interaction between transcription factors and epigenetic regulators which control stem cell fate. Epigenetic mechanisms are heritable alterations in genome function that do not involve changes in DNA sequence itself but that modulate gene expression, acting as mediators between the environment and the genome. At the molecular level, those epigenetic mechanisms comprise chemical modifications of DNA such as methylation, hydroxymethylation and histone modifications needed for the maintenance of NSC identity. Genomic imprinting is another normal epigenetic process leading to parental-specific expression of a gene, known to be implicated in the control of gene dosage in the neurogenic niches. The generation of induced pluripotent stem cells from NSCs by expression of defined transcription factors, provide key insights into fundamental principles of stem cell biology. Epigenetic modifications can also occur during reprogramming of NSCs to pluripotency and a better understanding of this process will help to elucidate the mechanisms required for stem cell maintenance. This review takes advantage of recent studies from the epigenetic field to report knowledge regarding the mechanisms of stemness maintenance of neural stem cells in the neurogenic niches. PMID:26029342

  14. Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

    PubMed

    Ogino, Takashi; Sawada, Masato; Takase, Hiroshi; Nakai, Chiemi; Herranz-Pérez, Vicente; Cebrián-Silla, Arantxa; Kaneko, Naoko; García-Verdugo, José Manuel; Sawamoto, Kazunobu

    2016-10-15

    In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991819

  15. GABAergic signalling in a neurogenic niche of the turtle spinal cord

    PubMed Central

    Reali, Cecilia; Fernández, Anabel; Radmilovich, Milka; Trujillo-Cenóz, Omar; Russo, Raúl E

    2011-01-01

    Abstract The region that surrounds the central canal (CC) in the turtle spinal cord is a neurogenic niche immersed within already functional circuits, where radial glia expressing brain lipid binding protein (BLBP) behave as progenitors. The behaviour of both progenitors and neuroblasts within adult neurogenic niches must be regulated to maintain the functional stability of the host circuit. In the brain, GABA plays a major role in this kind of regulation but little is known about GABAergic signalling in neurogenic niches of the postnatal spinal cord. Here we explored the action of GABA around the CC of the turtle spinal cord by combining patch-clamp recordings of CC-contacting cells, immunohistochemistry for key components of GABAergic signalling and Ca2+ imaging. Two potential sources of GABA appeared around the CC: GABAergic terminals and CC-contacting neurones. GABA depolarized BLBP+ progenitors via GABA transporter-3 (GAT3) and/or GABAA receptors. In CC-contacting neurones, GABAA receptor activation generated responses ranging from excitation to inhibition. This functional heterogeneity appeared to originate from different ratios of activity of the Na+–K+–2Cl− co-transporter (NKCC1) and the K+–Cl− co-transporter (KCC2). In both progenitors and immature neurones, GABA induced an increase in intracellular Ca2+ that required extracellular Ca2+ and was blocked by the selective GABAA receptor antagonist gabazine. Our study shows that GABAergic signalling around the CC shares fundamental properties with those in the embryo and adult neurogenic niches, suggesting that GABA may be part of the mechanisms regulating the production and integration of neurones within operational spinal circuits in the turtle. PMID:21911613

  16. Osteogenic and Neurogenic Stem Cells in Their Own Place: Unraveling Differences and Similarities Between Niches

    PubMed Central

    Lattanzi, Wanda; Parolisi, Roberta; Barba, Marta; Bonfanti, Luca

    2015-01-01

    Although therapeutic use of stem cells (SCs) is already available in some tissues (cornea, blood, and skin), in most organs we are far from reaching the translational goal of regenerative medicine. In the nervous system, due to intrinsic features which make it refractory to regeneration/repair, it is very hard to obtain functionally integrated regenerative outcomes, even starting from its own SCs (the neural stem cells; NSCs). Besides NSCs, mesenchymal stem cells (MSCs) have also been proposed for therapeutic purposes in neurological diseases. Yet, direct (regenerative) and indirect (bystander) effects are often confused, as are MSCs and bone marrow-derived (stromal, osteogenic) stem cells (BMSCs), whose plasticity is actually overestimated (i.e., trans-differentiation along non-mesodermal lineages, including neural fates). In order to better understand failure in the “regenerative” use of SCs for neurological disorders, it could be helpful to understand how NSCs and BMSCs have adapted to their respective organ niches. In this perspective, here the adult osteogenic and neurogenic niches are considered and compared within their in vivo environment. PMID:26635534

  17. Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche.

    PubMed

    Luarte, Alejandro; Bátiz, Luis Federico; Wyneken, Ursula; Lafourcade, Carlos

    2016-01-01

    Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

  18. Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

    PubMed Central

    Luarte, Alejandro; Bátiz, Luis Federico; Wyneken, Ursula; Lafourcade, Carlos

    2016-01-01

    Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future. PMID:27195011

  19. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    PubMed

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  20. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    PubMed Central

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system. PMID:26136659

  1. Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis.

    PubMed

    Solano Fonseca, Rene; Mahesula, Swetha; Apple, Deana M; Raghunathan, Rekha; Dugan, Allison; Cardona, Astrid; O'Connor, Jason; Kokovay, Erzsebet

    2016-04-01

    Neural stem cells (NSCs) exist throughout life in the ventricular-subventricular zone (V-SVZ) of the mammalian forebrain. During aging NSC function is diminished through an unclear mechanism. In this study, we establish microglia, the immune cells of the brain, as integral niche cells within the V-SVZ that undergo age-associated repositioning in the V-SVZ. Microglia become activated early before NSC deficits during aging resulting in an antineurogenic microenvironment due to increased inflammatory cytokine secretion. These age-associated changes were not observed in non-neurogenic brain regions, suggesting V-SVZ microglia are specialized. Using a sustained inflammatory model in young adult mice, we induced microglia activation and inflammation that was accompanied by reduced NSC proliferation in the V-SVZ. Furthermore, in vitro studies revealed secreted factors from activated microglia reduced proliferation and neuron production compared to secreted factors from resting microglia. Our results suggest that age-associated chronic inflammation contributes to declines in NSC function within the aging neurogenic niche. PMID:26857912

  2. Management options for sphincteric deficiency in adults with neurogenic bladder

    PubMed Central

    Mayer, Erik N.; Lenherr, Sara

    2016-01-01

    Neurogenic bladder is a very broad disease definition that encompasses varied disease and injury states affecting the bladder. The majority of patients with neurogenic bladder dysfunction do not have concomitant intrinsic sphincteric deficiency (ISD), but when this occurs the challenges of management of urinary incontinence from neurogenic bladder are compounded. There are no guidelines for surgical correction of ISD in adults and most of the literature on treatment of the problem comes from treatment of children with congenital diseases, such as myelomeningocele. Our goal, in this review, is to present some of the common surgical options for ISD [including artificial urinary sphincters, bladder slings, bladder neck reconstruction (BNR) and urethral bulking agents] and the evidence underlying these treatments in adults with neurogenic bladder. PMID:26904420

  3. Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body.

    PubMed

    Ortega-Sáenz, Patricia; Villadiego, Javier; Pardal, Ricardo; Toledo-Aral, Juan José; López-Barneo, José

    2015-01-01

    The carotid body (CB) is a polymodal chemoreceptor that triggers the hyperventilatory response to hypoxia necessary for the maintenance of O(2) homeostasis essential for the survival of organs such as the brain or heart. Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia, acidosis and, although less generally accepted, hypoglycemia. Current knowledge on CB function is mainly based on studies performed on lower mammals, but the information on the human CB is scant. Here we describe the structure, neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of CBs dissected from human cadavers. The adult CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. As reported for other mammalian species, glomus cells responded to hypoxia by external Ca(2+)-dependent increase of cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also responsive to hypoglycemia and together the two stimuli, hypoxia and hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of glomus cells are also preserved at an advanced age. Interestingly, a neurogenic niche similar to that recently described in rodents is also preserved in the adult human CB. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

  4. Mu Opioid Receptors Mediate the Effects of Chronic Ethanol Binge Drinking on the Hippocampal Neurogenic Niche

    PubMed Central

    Contet, Candice; Kim, Airee; Le, David; Iyengar, Siddharth; Kotzebue, Roxanne W.; Yuan, Clara J.; Kieffer, Brigitte L.; Mandyam, Chitra D.

    2013-01-01

    Ethanol exposure and withdrawal alter the generation of new neurons in the adult hippocampus. The endogenous opioid system, in particular the μ opioid receptor (MOR), can modulate neural progenitors and also plays a critical role in ethanol drinking and dependence. In the present study, we sought to determine whether MOR contributes to the effects of ethanol on the dentate gyrus (DG) neurogenic niche. MOR wild-type (WT), heterozygous (Het) and knockout (KO) littermates were subjected to voluntary ethanol drinking in repeated limited-access two-bottle choice (2BC) sessions. MOR deficiency did not alter progenitor proliferation, neuronal differentiation and maturation, apoptosis or microglia in ethanol-naïve mice. When exposed to five consecutive weeks of 2BC, MOR mutant mice exhibited a gene-dosage dependent reduction of ethanol consumption compared to WT mice. Introducing a week of ethanol deprivation between each week of 2BC increased ethanol consumption in all genotypes and produced equivalent intakes in WT, Het and KO mice. Under the latter paradigm, ethanol drinking decreased progenitor proliferation and neuronal differentiation in the DG of WT mice. Interestingly, WT mice exhibited a strong negative correlation between ethanol intake and proliferation, which was disrupted in Het and KO mice. Moreover, MOR deficiency blocked the effect of ethanol on neuronal differentiation. MOR deficiency also protected against the neuroimmune response to ethanol drinking. Finally, chronic binge drinking induced a paradoxical decrease in apoptosis, which was independent of MOR. Altogether our data suggest that MOR is implicated in some of the neuroplastic changes produced by chronic ethanol exposure in the DG. PMID:23461397

  5. The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late embryonic and post-embryonic nervous system development.

    PubMed

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient posterior

  6. The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late embryonic and post-embryonic nervous system development.

    PubMed

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient posterior

  7. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

    PubMed Central

    Salgado, Antonio J.; Sousa, Joao C.; Costa, Bruno M.; Pires, Ana O.; Mateus-Pinheiro, António; Teixeira, F. G.; Pinto, Luisa; Sousa, Nuno

    2015-01-01

    Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs. PMID:26217178

  8. NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche.

    PubMed

    Heng, Yee Hsieh Evelyn; Zhou, Bo; Harris, Lachlan; Harvey, Tracey; Smith, Aaron; Horne, Elise; Martynoga, Ben; Andersen, Jimena; Achimastou, Angeliki; Cato, Kathleen; Richards, Linda J; Gronostajski, Richard M; Yeo, Giles S; Guillemot, François; Bailey, Timothy L; Piper, Michael

    2015-10-01

    Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix(-/-) mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix(-/-) mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix(-/-) mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix(-/-) mice are smaller. We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche.

  9. Developmental cues and persistent neurogenic potential within an in vitro neural niche

    PubMed Central

    2010-01-01

    Background Neurogenesis, the production of neural cell-types from neural stem cells (NSCs), occurs during development as well as within select regions of the adult brain. NSCs in the adult subependymal zone (SEZ) exist in a well-categorized niche microenvironment established by surrounding cells and their molecular products. The components of this niche maintain the NSCs and their definitive properties, including the ability to self-renew and multipotency (neuronal and glial differentiation). Results We describe a model in vitro NSC niche, derived from embryonic stem cells, that produces many of the cells and products of the developing subventricular zone (SVZ) and adult SEZ NSC niche. We demonstrate a possible role for apoptosis and for components of the extracellular matrix in the maintenance of the NSC population within our niche cultures. We characterize expression of genes relevant to NSC self-renewal and the process of neurogenesis and compare these findings to gene expression produced by an established neural-induction protocol employing retinoic acid. Conclusions The in vitro NSC niche shows an identity that is distinct from the neurally induced embryonic cells that were used to derive it. Molecular and cellular components found in our in vitro NSC niche include NSCs, neural progeny, and ECM components and their receptors. Establishment of the in vitro NSC niche occurs in conjunction with apoptosis. Applications of this culture system range from studies of signaling events fundamental to niche formation and maintenance as well as development of unique NSC transplant platforms to treat disease or injury. PMID:20074373

  10. The Molecular Profiles of Neural Stem Cell Niche in the Adult Subventricular Zone

    PubMed Central

    Lee, Cheol; Hu, Jingqiong; Ralls, Sherry; Kitamura, Toshio; Loh, Y. Peng; Yang, Yanqin; Mukouyama, Yoh-suke; Ahn, Sohyun

    2012-01-01

    Neural stem cells (NSCs) reside in a unique microenvironment called the neurogenic niche and generate functional new neurons. The neurogenic niche contains several distinct types of cells and interacts with the NSCs in the subventricular zone (SVZ) of the lateral ventricle. While several molecules produced by the niche cells have been identified to regulate adult neurogenesis, a systematic profiling of autocrine/paracrine signaling molecules in the neurogenic regions involved in maintenance, self-renewal, proliferation, and differentiation of NSCs has not been done. We took advantage of the genetic inducible fate mapping system (GIFM) and transgenic mice to isolate the SVZ niche cells including NSCs, transit-amplifying progenitors (TAPs), astrocytes, ependymal cells, and vascular endothelial cells. From the isolated cells and microdissected choroid plexus, we obtained the secretory molecule expression profiling (SMEP) of each cell type using the Signal Sequence Trap method. We identified a total of 151 genes encoding secretory or membrane proteins. In addition, we obtained the potential SMEP of NSCs using cDNA microarray technology. Through the combination of multiple screening approaches, we identified a number of candidate genes with a potential relevance for regulating the NSC behaviors, which provide new insight into the nature of neurogenic niche signals. PMID:23209762

  11. Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain.

    PubMed

    Wagenführ, Lisa; Meyer, Anne Karen; Marrone, Lara; Storch, Alexander

    2016-02-01

    Oxygen tension is an important factor controlling stem cell proliferation and maintenance in various stem cell populations with a particular relevance in midbrain dopaminergic progenitors. Further studies have shown that the oxygen-dependent transcription factor hypoxia-inducible factor 1α (HIF-1α) is involved in these processes. However, all available studies on oxygen effects in dopaminergic neuroprogenitors were performed in vitro and thus it remains unclear whether tissue oxygen tension in the embryonic midbrain is also relevant for the regulation of dopaminergic neurogenesis in vivo. We thus dissect here the effects of oxygen tension in combination with HIF-1α conditional knockout on dopaminergic neurogenesis by using a novel experimental design allowing for the control of oxygen tension within the microenvironment of the neurogenic niche of the murine fetal midbrain in vivo. The microenvironment of the midbrain dopaminergic neurogenic niche was detected as hypoxic with oxygen tensions below 1.1%. Maternal oxygen treatment of 10%, 21%, and 75% atmospheric oxygen tension for 48 h translates into robust changes in fetal midbrain oxygenation. Fetal midbrain hypoxia hampered the generation of dopaminergic neurons and is accompanied with restricted fetal midbrain development. In contrast, induced hyperoxia stimulated proliferation and differentiation of dopaminergic progenitors during early and late embryogenesis. Oxygen effects were not directly mediated through HIF-1α signaling. These data--in agreement with in vitro data-indicate that oxygen is a crucial regulator of developmental dopaminergic neurogenesis. Our study provides the initial framework for future studies on molecular mechanisms mediating oxygen regulation of dopaminergic neurogenesis within the fetal midbrain as its natural environment.

  12. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.

    PubMed

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα(-/-) mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα(-/-) mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα(-/-)-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα(-/-) mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.

  13. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.

    PubMed

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα(-/-) mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα(-/-) mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα(-/-)-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα(-/-) mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments. PMID:27013951

  14. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches

    PubMed Central

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J.; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα−/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα−/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα−/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα−/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments. PMID:27013951

  15. Hypothalamic subependymal niche: a novel site of the adult neurogenesis.

    PubMed

    Rojczyk-Gołębiewska, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2014-07-01

    The discovery of undifferentiated, actively proliferating neural stem cells (NSCs) in the mature brain opened a brand new chapter in the contemporary neuroscience. Adult neurogenesis appears to occur in specific brain regions (including hypothalamus) throughout vertebrates' life, being considered an important player in the processes of memory, learning, and neural plasticity. In the adult mammalian brain, NSCs are located mainly in the subgranular zone (SGZ) of the hippocampal dentate gyrus and in the subventricular zone (SVZ) of the lateral ventricle ependymal wall. Besides these classical regions, hypothalamic neurogenesis occurring mainly along and beneath the third ventricle wall seems to be especially well documented. Neurogenic zones in SGZ, SVZ, and in the hypothalamus share some particular common features like similar cellular cytoarchitecture, vascularization pattern, and extracellular matrix properties. Hypothalamic neurogenic niche is formed mainly by four special types of radial glia-like tanycytes. They are characterized by distinct expression of some neural progenitor and stem cell markers. Moreover, there are numerous suggestions that newborn hypothalamic neurons have a significant ability to integrate into the local neural pathways and to play important physiological roles, especially in the energy balance regulation. Newly formed neurons in the hypothalamus can synthesize and release food intake regulating neuropeptides and they are sensitive to the leptin. On the other hand, high-fat diet positively influences hypothalamic neurogenesis in rodents. The nature of this intriguing new site of adult neurogenesis is still so far poorly studied and requires further investigations.

  16. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

    PubMed Central

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

    2015-01-01

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

  17. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain.

    PubMed

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R; Killinger, Bryan A

    2015-10-14

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum.

  18. The ‘Ventral Organs’ of Pycnogonida (Arthropoda) Are Neurogenic Niches of Late Embryonic and Post-Embryonic Nervous System Development

    PubMed Central

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions – traditionally designated as ‘ventral organs’ – detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons – as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient

  19. Large-scale live imaging of adult neural stem cells in their endogenous niche

    PubMed Central

    Dray, Nicolas; Bedu, Sébastien; Vuillemin, Nelly; Alunni, Alessandro; Coolen, Marion; Krecsmarik, Monika; Supatto, Willy; Beaurepaire, Emmanuel; Bally-Cuif, Laure

    2015-01-01

    Live imaging of adult neural stem cells (aNSCs) in vivo is a technical challenge in the vertebrate brain. Here, we achieve long-term imaging of the adult zebrafish telencephalic neurogenic niche and track a population of >1000 aNSCs over weeks, by taking advantage of fish transparency at near-infrared wavelengths and of intrinsic multiphoton landmarks. This methodology enables us to describe the frequency, distribution and modes of aNSCs divisions across the entire germinal zone of the adult pallium, and to highlight regional differences in these parameters. PMID:26395477

  20. IFN gamma regulates proliferation and neuronal differentiation by STAT1 in adult SVZ niche.

    PubMed

    Pereira, Leticia; Medina, Rebeca; Baena, Miguel; Planas, Anna M; Pozas, Esther

    2015-01-01

    The adult subventricular zone (SVZ) is the main neurogenic niche in normal adult brains of mice and rats. Interferon gamma (IFNγ) has somewhat controversially been associated with SVZ progenitor proliferation and neurogenesis. The in vivo involvement of IFNγ in the physiology of the adult SVZ niche is not fully understood and its intracellular mediators are unknown. Here we show that IFNγ, through activation of its canonical signal transducer and activator of transcription 1 (STAT1) pathway, acts specifically on Nestin+ progenitors by decreasing both progenitor proliferation and the number of cycling cells. In addition, IFNγ increases the number of neuroblasts generated without shifting glial fate determination. The final result is deficient recruitment of newborn neurons to the olfactory bulb (OB), indicating that IFNγ-induced stimulation of neuronal differentiation does not compensate for its antiproliferative effect. We conclude that IFNγ signaling via STAT1 in the SVZ acts dually as an antiproliferative and proneurogenic factor, and thereby regulates neurogenesis in normal adult brains.

  1. Cyp26b1 mediates differential neurogenicity in axial-specific populations of adult spinal cord progenitor cells.

    PubMed

    Leung, Carly; Chan, Sherwin Chun Leung; Tsang, Sze Lan; Wu, Wutian; Sham, Mai Har

    2012-08-10

    Utilization of endogenous adult spinal cord progenitor cells (SCPCs) for neuronal regeneration is a promising strategy for spinal cord repair. To mobilize endogenous SCPCs for injury repair, it is necessary to understand their intrinsic properties and to identify signaling factors that can stimulate their neurogenic potential. In this study, we demonstrate that adult mouse SCPCs express distinct combinatorial Hox genes and exhibit axial-specific stem cell properties. Lumbar-derived neurospheres displayed higher primary sphere formation and greater neurogenicity compared with cervical- and thoracic-derived neurospheres. To further understand the mechanisms governing neuronal differentiation of SCPCs from specific axial regions, we examined the neurogenic responses of adult SCPCs to retinoic acid (RA), an essential factor for adult neurogenesis. Although RA is a potent inducer of neuronal differentiation, we found that RA enhanced the generation of neurons specifically in cervical- but not lumbar-derived cells. We further demonstrate that the differential RA response was mediated by the RA-degrading enzyme cytochrome P450 oxidase b1 Cyp26b1. Lumbar cells express high levels of Cyp26b1 and low levels of the RA-synthesizing enzyme retinaldehyde dehydrogenase Raldh2, resulting in limited activation of the RA signaling pathway in these cells. In contrast, low Cyp26b1 expression in cervical spinal cord progenitor cells allows RA signaling to be readily activated upon RA treatment. The intrinsic heterogeneity and signaling factor regulation among adult SCPCs suggest that different niche factor regimens are required for site-specific mobilization of endogenous SCPCs from distinct spatial regions of the spinal cord for injury repair.

  2. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    PubMed

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  3. A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain.

    PubMed

    Choi, Minee L; Begeti, Faye; Barker, Roger A; Kim, Namho

    2016-04-01

    Adult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting methodology. However, this type of approach fails to capture the dynamic aspects of the neurogenic process, where neural proliferation, death and differentiation take place continuously and simultaneously. In this paper, we propose a simple mathematical approach to better understand the adult neurogenic process in the hippocampus which in turn will allow for a better analysis of this process in disease states and following drug therapies. PMID:26443687

  4. IFN gamma regulates proliferation and neuronal differentiation by STAT1 in adult SVZ niche

    PubMed Central

    Pereira, Leticia; Medina, Rebeca; Baena, Miguel; Planas, Anna M.; Pozas, Esther

    2015-01-01

    The adult subventricular zone (SVZ) is the main neurogenic niche in normal adult brains of mice and rats. Interferon gamma (IFNγ) has somewhat controversially been associated with SVZ progenitor proliferation and neurogenesis. The in vivo involvement of IFNγ in the physiology of the adult SVZ niche is not fully understood and its intracellular mediators are unknown. Here we show that IFNγ, through activation of its canonical signal transducer and activator of transcription 1 (STAT1) pathway, acts specifically on Nestin+ progenitors by decreasing both progenitor proliferation and the number of cycling cells. In addition, IFNγ increases the number of neuroblasts generated without shifting glial fate determination. The final result is deficient recruitment of newborn neurons to the olfactory bulb (OB), indicating that IFNγ-induced stimulation of neuronal differentiation does not compensate for its antiproliferative effect. We conclude that IFNγ signaling via STAT1 in the SVZ acts dually as an antiproliferative and proneurogenic factor, and thereby regulates neurogenesis in normal adult brains. PMID:26217191

  5. Congenital causes of neurogenic bladder and the transition to adult care

    PubMed Central

    Loftus, Christopher J.

    2016-01-01

    The population of patients with congenital genitourinary disorders has unique healthcare demands that require an additional interpersonal and medical skillset. Adults with congenital neurogenic bladder may have complex urinary anatomy, abnormal bladder function and atypical voiding mechanisms. While initial surgery and care of these patients is typically managed by a pediatric urologist, growth and development into adulthood necessitates transition of care to an adult care team. Failure of transition to adult care has been demonstrated to result in lower quality healthcare and increased risk of developing preventable complications. PMID:26904411

  6. Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer's Disease.

    PubMed

    Hamilton, Laura K; Dufresne, Martin; Joppé, Sandra E; Petryszyn, Sarah; Aumont, Anne; Calon, Frédéric; Barnabé-Heider, Fanie; Furtos, Alexandra; Parent, Martin; Chaurand, Pierre; Fernandes, Karl J L

    2015-10-01

    Lipid metabolism is fundamental for brain development and function, but its roles in normal and pathological neural stem cell (NSC) regulation remain largely unexplored. Here, we uncover a fatty acid-mediated mechanism suppressing endogenous NSC activity in Alzheimer's disease (AD). We found that postmortem AD brains and triple-transgenic Alzheimer's disease (3xTg-AD) mice accumulate neutral lipids within ependymal cells, the main support cell of the forebrain NSC niche. Mass spectrometry and microarray analyses identified these lipids as oleic acid-enriched triglycerides that originate from niche-derived rather than peripheral lipid metabolism defects. In wild-type mice, locally increasing oleic acid was sufficient to recapitulate the AD-associated ependymal triglyceride phenotype and inhibit NSC proliferation. Moreover, inhibiting the rate-limiting enzyme of oleic acid synthesis rescued proliferative defects in both adult neurogenic niches of 3xTg-AD mice. These studies support a pathogenic mechanism whereby AD-induced perturbation of niche fatty acid metabolism suppresses the homeostatic and regenerative functions of NSCs.

  7. Neurogenic and non-neurogenic functions of endogenous neural stem cells

    PubMed Central

    Butti, Erica; Cusimano, Melania; Bacigaluppi, Marco; Martino, Gianvito

    2014-01-01

    Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic markers. The precise tracing of neural stem/progenitor cells (NPCs) was therefore, not properly feasible. After the (partial) identification of those markers, it was the lack of specific tools that hindered a proper experimental elimination and tracing of those cells to demonstrate their terminal fate and commitment. Nowadays, irradiation, cytotoxic drugs as well as genetic tracing/ablation procedures have moved the field forward and increased our understanding of neurogenesis processes in both physiological and pathological conditions. Newly formed NPC progeny from the SVZ can replace granule cells in the olfactory bulbs of rodents, thus contributing to orchestrate sophisticated odor behavior. SGZ-derived new granule cells, instead, integrate within the DG where they play an essential role in memory functions. Furthermore, converging evidence claim that endogenous NPCs not only exert neurogenic functions, but might also have non-neurogenic homeostatic functions by the release of different types of neuroprotective molecules. Remarkably, these non-neurogenic homeostatic functions seem to be necessary, both in healthy and diseased conditions, for example for preventing or limiting tissue damage. In this review, we will discuss the neurogenic and the non-neurogenic functions of adult NPCs both in physiological and pathological conditions. PMID:24808821

  8. Axonal control of the adult neural stem cell niche.

    PubMed

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D; Tecott, Laurence H; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-04-01

    The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain's neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  9. Axonal Control of the Adult Neural Stem Cell Niche

    PubMed Central

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  10. Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites

    PubMed Central

    Capilla-Gonzalez, Vivian; Gil-Perotin, Sara; Ferragud, Antonio; Bonet-Ponce, Luis; Canales, Juan Jose; Garcia-Verdugo, Jose Manuel

    2012-01-01

    Background Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. Methodology/Principal Findings 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively. Conclusions/Significance The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits. PMID:22238669

  11. Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults

    PubMed Central

    Peterson, Andrew Charles

    2016-01-01

    The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision-making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson’s, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction. PMID:26904410

  12. Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults.

    PubMed

    Allio, Bryce Andrew; Peterson, Andrew Charles

    2016-02-01

    The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision-making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson's, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction. PMID:26904410

  13. The fundamental thermal niche of adult landlocked striped bass

    USGS Publications Warehouse

    Bettoli, P.W.

    2005-01-01

    Researchers have described the temperatures selected by landlocked striped bass Morone saxatilis in different locales throughout the USA. However, seasonally low concentrations of dissolved oxygen (DO) in many systems prevented striped bass from using the cool waters (<22??C) they may have preferred. In Melton Hill Reservoir, a 92-km-long impoundment on the Clinch River in east Tennessee, 15 adult striped bass were tagged with temperature-sensing radio tags and tracked for an average of 418 d in 1999-2000. Cold, hypolimnetic discharges from an upstream dam and heated discharge from a steam-generating electric facility near the midpoint of this run-of-the-river reservoir provided a broad range of temperatures in most seasons, and hypoxic habitats were uncommon even during stratification. The mean temperature occupied by striped bass varied seasonally (repeated-measures analysis of variance, P < 0.0001) and was highest in summer (17.5??C), intermediate in spring and fall (15.4-16.9??C), and lowest in winter (13.0??C). The mean and modal temperatures occupied during the growing season (May-October 1999) were 17.5??C and 19.0??C, respectively; 30% of the observations were between 9??C and 15??C. These data indicate that the fundamental thermal niche of adult landlocked striped bass may be lower than literature estimates. These results also represent the first unbiased field estimates of the influence of season on the thermal ecology of adult striped bass. The thermal characteristics of habitats considered optimal in habitat suitability index models for adult landlocked striped bass (i.e., 18-24??C) should be revised to include cooler waters. ?? Copyright by the American Fisheries Society 2005.

  14. Discerning Neurogenic vs. Non-Neurogenic Postnatal Lateral Ventricular Astrocytes via Activity-Dependent Input

    PubMed Central

    Adlaf, Elena W.; Mitchell-Dick, Aaron; Kuo, Chay T.

    2016-01-01

    Throughout development, neural stem cells (NSCs) give rise to differentiated neurons, astrocytes, and oligodendrocytes which together modulate perception, memory, and behavior in the adult nervous system. To understand how NSCs contribute to postnatal/adult brain remodeling and repair after injury, the lateral ventricular (LV) neurogenic niche in the rodent postnatal brain serves as an excellent model system. It is a specialized area containing self-renewing GFAP+ astrocytes functioning as NSCs generating new neurons throughout life. In addition to this now well-studied regenerative process, the LV niche also generates differentiated astrocytes, playing an important role for glial scar formation after cortical injury. While LV NSCs can be clearly distinguished from their neuroblast and oligodendrocyte progeny via molecular markers, the astrocytic identity of NSCs has complicated their distinction from terminally-differentiated astrocytes in the niche. Our current models of postnatal/adult LV neurogenesis do not take into account local astrogenesis, or the possibility that cellular markers may be similar between non-dividing GFAP+ NSCs and their differentiated astrocyte daughters. Postnatal LV neurogenesis is regulated by NSC-intrinsic mechanisms interacting with extracellular/niche-driven cues. It is generally believed that these local effects are responsible for sustaining neurogenesis, though behavioral paradigms and disease states have suggested possibilities for neural circuit-level modulation. With recent experimental findings that neuronal stimulation can directly evoke responses in LV NSCs, it is possible that this exciting property will add a new dimension to identifying postnatal/adult NSCs. Here, we put forth a notion that neural circuit-level input can be a distinct characteristic defining postnatal/adult NSCs from non-neurogenic astroglia. PMID:27047330

  15. Same size--same niche? Foraging niche separation between sympatric juvenile Galapagos sea lions and adult Galapagos fur seals.

    PubMed

    Jeglinski, Jana W E; Goetz, Kimberley T; Werner, Christiane; Costa, Daniel P; Trillmich, Fritz

    2013-05-01

    1. In vertebrates, patterns of resource utilization change throughout development according to age- and or size-specific abilities and requirements. Thus, interspecific competition affects different age classes differently. 2. Adults of sympatric species often show distinct foraging niche segregation, but juvenile resource use might overlap with adult competitors of similar body size. Resultant negative effects on juveniles can have important consequences for population dynamics, yet such interactions have received little attention in studies of mammalian communities. 3. Using GPS tracking devices, time-depth recorders and stable isotope data, we compared diving depth, activity time, trophic position and foraging habitat characteristics to investigate foraging niche overlap between similar-sized sympatric juvenile Galapagos sea lions (Zalophus wollebaeki) and adult Galapagos fur seals (Arctocephalus galapagoensis) and compared each group with much larger-bodied adult Galapagos sea lions. 4. We found little indication for direct competition but a complex pattern of foraging niche segregation: juvenile sea lions and adult fur seals dived to shallow depths at night, but foraged in different habitats with limited spatial overlap. Conversely, juvenile and adult sea lions employed different foraging patterns, but their foraging areas overlapped almost completely. 5. Consistency of foraging habitat characteristics between juvenile and adult sea lions suggests that avoidance of competition may be important in shaping foraging habitat utilization. Resultant specialization on a limited habitat could contribute to low sea lion numbers that contrast with high fur seal abundance. Our data suggest that exploitation by multiple predators within spatially restricted foraging ranges of juveniles might negatively impact juvenile foraging success and ultimately influence population dynamics.

  16. Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors.

    PubMed

    Seaberg, Raewyn M; van der Kooy, Derek

    2002-03-01

    Neurogenesis persists in two adult brain regions: the ventricular subependyma and the subgranular cell layer in the hippocampal dentate gyrus (DG). Previous work in many laboratories has shown explicitly that multipotential, self-renewing stem cells in the subependyma are the source of newly generated migrating neurons that traverse the rostral migratory stream and incorporate into the olfactory bulb as interneurons. These stem cells have been specifically isolated from the subependyma, and their properties of self-renewal and multipotentiality have been demonstrated in vitro. In contrast, it is a widely held assumption that the "hippocampal" stem cells that can be isolated in vitro from adult hippocampus reside in the neurogenic subgranular layer and represent the source of new granule cell neurons, but this has never been tested directly. Primary cell isolates derived from the precise microdissection of adult rodent neurogenic regions were compared using two very different commonly used culture methods: a clonal colony-forming (neurosphere) assay and a monolayer culture system. Importantly, both of these culture methods generated the same conclusion: stem cells can be isolated from hippocampus-adjacent regions of subependyma, but the adult DG proper does not contain a population of resident neural stem cells. Indeed, although the lateral ventricle and other ventricular subependymal regions directly adjacent to the hippocampus contain neural stem cells that exhibit long-term self-renewal and multipotentiality, separate neuronal and glial progenitors with limited self-renewal capacity are present in the adult DG, suggesting that neuron-specific progenitors and not multipotential stem cells are the source of newly generated DG neurons throughout adulthood.

  17. Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

    PubMed Central

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

  18. Laparoscopic excision of mesenteric duplication enteric cyst embedded in sigmoid mesocolon mimicking retroperitoneal neurogenic tumor in adults.

    PubMed

    Wang, Jui-Ho; Lin, Jen-Tai; Hsu, Chao-Wen

    2012-10-01

    Mesenteric cysts are rare abdominal tumors with an incidence of 1/105,000 to 250,000 hospitalized adult surgical patients. These cysts may occur in every part of the mesentery, from duodenum to rectum. Most frequently, cysts are localized in small bowel mesentery. They usually present during the first decade of life, mostly occurring in pediatric patients. These lesions characteristically arise from the mesenteric border of the bowel. The majority are asymptomatic and, if found, are discovered incidentally during abdominal exploration or radiologic examination. Traditionally, the treatment of mesenteric cyst is surgical excision by laparotomy. However, in 1993, Mackenzie described the first laparoscopic excision of a mesenteric cyst. Since then, several cases have been reported but mainly in small intestine. Here, we reported an adult patient of a mesenteric duplication enteric cyst embedded in sigmoid mesocolon mimicking retroperitoneal neurogenic tumor, which was completely excised using the laparoscopic approach (Supplemental Digital Content 1, http://links.lww.com/SLE/A73).

  19. The master negative regulator REST/NRSF controls adult neurogenesis by restraining the neurogenic program in quiescent stem cells.

    PubMed

    Gao, Zhengliang; Ure, Kerstin; Ding, Peiguo; Nashaat, Mostafa; Yuan, Laura; Ma, Jing; Hammer, Robert E; Hsieh, Jenny

    2011-06-29

    Transcriptional regulation is a critical mechanism in the birth, specification, and differentiation of granule neurons in the adult hippocampus. One of the first negative-acting transcriptional regulators implicated in vertebrate development is repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF)--thought to regulate hundreds of neuron-specific genes--yet its function in the adult brain remains elusive. Here we report that REST/NRSF is required to maintain the adult neural stem cell (NSC) pool and orchestrate stage-specific differentiation. REST/NRSF recruits CoREST and mSin3A corepressors to stem cell chromatin for the regulation of pro-neuronal target genes to prevent precocious neuronal differentiation in cultured adult NSCs. Moreover, mice lacking REST/NRSF specifically in NSCs display a transient increase in adult neurogenesis that leads to a loss in the neurogenic capacity of NSCs and eventually diminished granule neurons. Our work identifies REST/NRSF as a master negative regulator of adult NSC differentiation and offers a potential molecular target for neuroregenerative approaches. PMID:21715642

  20. Neurogenic Bladder

    PubMed Central

    Dorsher, Peter T.; McIntosh, Peter M.

    2012-01-01

    Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

  1. Technological applications in the assessment of acquired neurogenic communication and swallowing disorders in adults.

    PubMed

    Hallowell, B; Katz, R C

    1999-01-01

    The role of technology is expanding rapidly in many aspects of the diagnostic process with patients who have neurogenic communication and swallowing disorders. In this article we discuss a broad selection of technological tools that enhance a wide range of diagnostic tasks, such as taking case histories, administering and scoring tests, performing acoustic, physiologic, cognitive, and linguistic analyses, making normative comparisons, profiling diagnostic results, and making diagnostic decisions. Clinicians are encouraged to scrutinize the relative value of all diagnostic tools to maintaining the quality of service. An appendix includes information for contacting vendors and manufacturers of the products discussed.

  2. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis.

    PubMed

    DeFalco, Tony; Potter, Sarah J; Williams, Alyna V; Waller, Brittain; Kan, Matthew J; Capel, Blanche

    2015-08-18

    The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs). Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1) and enzymes involved in retinoic acid (RA) biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  3. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    PubMed Central

    DeFalco, Tony; Potter, Sarah J.; Williams, Alyna V.; Waller, Brittain; Kan, Matthew J.; Capel, Blanche

    2015-01-01

    Summary The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs). Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony stimulating factor 1 (CSF1) and enzymes involved in retinoic acid (RA) biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis, and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues. PMID:26257171

  4. Neurogenic cough.

    PubMed

    Altman, Kenneth W; Noordzij, J Pieter; Rosen, Clark A; Cohen, Seth; Sulica, Lucian

    2015-07-01

    We review contemporary concepts of the pathophysiology of neurogenic cough, and its evaluation and treatment based on scientific publications addressing neurogenic cough. Neurogenic cough is thought to be the result of sensory neuropathy, most commonly idiopathic. Because it is principally a sensory phenomenon, clinical evaluation is challenging, the diagnosis most often being made by exclusion. Identification of motor paresis, either by laryngoscopy or laryngeal electromyography, may suggest the presence of sensory neuropathy. The utility of amitriptyline and gabapentin has been demonstrated in randomized clinical trials, and retrospective series and case reports have suggested efficacy of pregabalin, baclofen, and botulinum toxin. Sensory neuropathy appears to be an important cause of chronic refractory cough, and appears amenable to treatment with a variety of pharmacologic agents.

  5. Obesity-dependent cannabinoid modulation of proliferation in adult neurogenic regions.

    PubMed

    Rivera, Patricia; Romero-Zerbo, Yanina; Pavón, Francisco J; Serrano, Antonia; López-Ávalos, María-Dolores; Cifuentes, Manuel; Grondona, Jesús-Mateos; Bermúdez-Silva, Francisco-Javier; Fernández-Llebrez, Pedro; de Fonseca, Fernando R; Suárez, Juan; Pérez-Martín, Margarita

    2011-05-01

    Endocannabinoid signalling participates in the control of neurogenesis, especially after brain insults. Obesity may explain alterations in physiology affecting neurogenesis, although it is unclear whether cannabinoid signalling may modulate neural proliferation in obese animals. Here we analyse the impact of obesity by using two approaches, a high-fat diet (HFD, 60% fat) and a standard/low-fat diet (STD, 10% fat), and the response to a subchronic treatment with the cannabinoid receptor type 1 (CB1) inverse agonist AM251 (3 mg/kg) on cell proliferation of two relevant neurogenic regions, namely the subventricular zone in the striatal wall of the lateral ventricle (SVZ) and the subgranular zone of the dentate gyrus (SGZ), and also in the hypothalamus given its role in energy metabolism. We found evidence of an interaction between diet-induced obesity and CB1 signalling in the regulation of cell proliferation. AM251 reduced caloric intake and body weight in obese rats, as well as corrected plasma levels of cholesterol and triglycerides. AM251 is shown, for the first time, to modulate cell proliferation in HFD-obese rats only. We observed an increase in the number of 5-bromo-2-deoxyuridine-labelled (BrdU+) cells in the SGZ, but a decrease in the number of BrdU+ cells in the SVZ and the hypothalamus of AM251-treated HFD rats. These BrdU+ cells expressed the neuron-specific βIII-tubulin. These results suggest that obesity may impact cell proliferation in the brain selectively, and provide support for a role of CB1 signalling regulation of neurogenesis in response to obesity.

  6. The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury

    PubMed Central

    Jones, Kathryn S; Connor, Bronwen J

    2016-01-01

    Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over-expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over-expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration. PMID:27397999

  7. The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain

    PubMed Central

    Galvez-Contreras, Alma Y.; Quiñones-Hinojosa, Alfredo; Gonzalez-Perez, Oscar

    2013-01-01

    In the adult brain, multipotent progenitor cells have been identified in three areas: the ventricular-subventricular zone (VZ-SVZ), adjacent to the striatal wall of the lateral ventricles, the subgranular zone (SGZ), located at the dentate gyrus of the hippocampus and the subcallosal zone (SCZ), located between the corpus callosum and the CA1 and CA2 regions of the hippocampus. The neural progenitor cells of these regions express the epidermal growth factor receptor (EGFR, ErbB-1 or HER1). EGF, the most important ligand for the EGFR, is a potent mitogenic agent that stimulates proliferation, survival, migration and differentiation into the oligodendrocyte lineage. Other ErbB receptors also activate several intracellular pathways for oligodendrocyte specification, migration and survival. However, the specific downstream pathways related to oligodendrogenesis and the hierarchic interaction among intracellular signaling cascades is not well-known. We summarize the current data regarding the role of EGFR and ErbB family signaling on neural stem cells and the downstream cascades involved in oligodendrogenesis in the neurogenic niches of the adult brain. Understanding the mechanisms that regulate proliferation, differentiation, migration of oligodendrocytes and myelination is of critical importance for the field of neurobiology and constitutes a crucial step in the design of stem-cell-based therapies for demyelinating diseases. PMID:24381541

  8. Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila.

    PubMed

    Aradhya, Rajaguru; Zmojdzian, Monika; Da Ponte, Jean Philippe; Jagla, Krzysztof

    2015-12-09

    How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs.

  9. Pharmacotherapy for neurogenic detrusor overactivity.

    PubMed

    Chancellor, Michael B; Anderson, Rodney U; Boone, Timothy B

    2006-06-01

    Chancellor MB, Anderson RU, Boone TB: Pharmacotherapy for neurogenic detrusor overactivity. Am J Phys Med Rehabil 2006;85:536-545. Patients with neurogenic detrusor overactivity are a heterogeneous group with voiding dysfunction secondary to neurologic injury or disease. The neurogenic detrusor overactivity syndrome, which may include urinary frequency, urgency, and incontinence, frequently contributes to a loss of independence, or even institutionalization. Urodynamic assessment provides the best method of quantifying and classifying neurogenic detrusor overactivity dysfunction in patients with primary diagnoses as diverse as Parkinson's disease, cerebral palsy, multiple sclerosis, spinal cord injury, and spina bifida. For many patients, management of urinary symptoms includes pharmacotherapy with an anticholinergic agent. Several novel approaches to managing neurogenic detrusor overactivity, including intravesical instillation of anticholinergic agents, vanilloids, and neurotoxins, are being investigated. For most patients, however, flexible dosing with an anticholinergic agent, with clean intermittent catheterization when indicated, has been shown to reduce the risks of urologic complications, improve levels of continence, and enhance patient quality of life in both children and adults.

  10. Identification of a Sustained Neurogenic Zone at the Dorsal Surface of the Adult Mouse Hippocampus and Its Regulation by the Chemokine SDF-1

    PubMed Central

    Belmadani, Abdelhak; Ren, Dongjun; Bhattacharyya, Bula J.; Rothwangl, Katharina B.; Hope, Thomas J.; Perlman, Harris; Miller, Richard J.

    2015-01-01

    We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the “subhippocampal zone,” SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology. PMID:25656357

  11. Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF-1.

    PubMed

    Belmadani, Abdelhak; Ren, Dongjun; Bhattacharyya, Bula J; Rothwangl, Katharina B; Hope, Thomas J; Perlman, Harris; Miller, Richard J

    2015-11-01

    We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the "subhippocampal zone," SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology.

  12. Sexual dimorphism in venom chemistry in Tetragnatha spiders is not easily explained by adult niche differences.

    PubMed

    Binford, Greta J; Gillespie, Rosemary G; Maddison, Wayne P

    2016-05-01

    Spider venom composition typically differs between sexes. This pattern is anecdotally thought to reflect differences in adult feeding biology. We used a phylogenetic approach to compare intersexual venom dimorphism between species that differ in adult niche dimorphism. Male and female venoms were compared within and between related species of Hawaiian Tetragnatha, a mainland congener, and outgroups. In some species of Hawaiian Tetragnatha adult females spin orb-webs and adult males capture prey while wandering, while in other species both males and females capture prey by wandering. We predicted that, if venom sexual dimorphism is primarily explained by differences in adult feeding biology, species in which both sexes forage by wandering would have monomorphic venoms or venoms with reduced dimorphism relative to species with different adult feeding biology. However, we found striking sexual dimorphism in venoms of both wandering and orb-weaving Tetragnatha species with males having high molecular weight components in their venoms that were absent in females, and a reduced concentration of low molecular weight components relative to females. Intersexual differences in venom composition within Tetragnatha were significantly larger than in non-Tetragnatha species. Diet composition was not different between sexes. This striking venom dimorphism is not easily explained by differences in feeding ecology or behavior. Rather, we hypothesize that the dimorphism reflects male-specific components that play a role in mating biology possibly in sexual stimulation, nuptial gifts and/or mate recognition.

  13. Neurogenic Hyperadrenergic Orthostatic Hypotension – A Newly-recognized Variant of Orthostatic Hypotension in Older Adults with Elevated Norepinephrine

    PubMed Central

    Mar, Philip L; Shibao, Cyndya A.; Garland, Emily M; Black, Bonnie K; Biaggioni, Italo; Diedrich, André; Paranjape, Sachin Y; Robertson, David; Raj, Satish R

    2015-01-01

    Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine. We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma norepinephrine. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based upon standing norepinephrine, patients were dichotomized into a hyperadrenergic orthostatic hypotension group (hyperOH: upright NE ≥3.55 nmol/L [600 pg/mL], n=19) or a non-hyperadrenergic orthostatic hypotension group (nOH: upright NE < 3.55 nmol/L [600 pg/mL], n=64). Medical history and data from autonomic testing, including the Valsalva maneuver (VM), were analyzed. HyperOH patients had profound orthostatic falls in blood pressure, but less severe than in nOH (change in SBP: −53±31 mmHg vs. −68±33 mmHg, P=0.050; change in DBP: −18±23 mmHg vs. −30±17 mmHg, P=0.01). The expected compensatory increase in standing heart rate was similarly blunted in both hyperOH and nOH groups (84±15 bpm vs. 82±14 bpm; P=0.6). HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM, and a shorter VM phase 4 blood pressure recovery time (16.5±8.9 sec vs. 31.6±16.6 sec; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic orthostatic hypotension, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand if hyperOH patients will progress to nOH or if this represents a different disorder. PMID:25706983

  14. Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila

    PubMed Central

    Aradhya, Rajaguru; Zmojdzian, Monika; Da Ponte, Jean Philippe; Jagla, Krzysztof

    2015-01-01

    How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs. DOI: http://dx.doi.org/10.7554/eLife.08497.001 PMID:26650355

  15. Neuromodulation in neurogenic bladder

    PubMed Central

    Sanford, Melissa T.

    2016-01-01

    While neuromodulation is a well-established treatment option for patients with non-neurogenic overactive bladder and urinary retention, its applicability to the neurogenic bladder population has only recently been examined more in depth. In this article we will discuss the outcomes, contraindications, and special considerations of sacral and percutaneous tibial nerve stimulation (PTNS) in patients with neurogenic lower urinary tract dysfunction. PMID:26904417

  16. Vascular-derived TGF-β increases in the stem cell niche and perturbs neurogenesis during aging and following irradiation in the adult mouse brain

    PubMed Central

    Pineda, Jose R; Daynac, Mathieu; Chicheportiche, Alexandra; Cebrian-Silla, Arantxa; Sii Felice, Karine; Garcia-Verdugo, Jose Manuel; Boussin, François D; Mouthon, Marc-André

    2013-01-01

    Neurogenesis decreases during aging and following cranial radiotherapy, causing a progressive cognitive decline that is currently untreatable. However, functional neural stem cells remained present in the subventricular zone of high dose-irradiated and aged mouse brains. We therefore investigated whether alterations in the neurogenic niches are perhaps responsible for the neurogenesis decline. This hypothesis was supported by the absence of proliferation of neural stem cells that were engrafted into the vascular niches of irradiated host brains. Moreover, we observed a marked increase in TGF-β1 production by endothelial cells in the stem cell niche in both middle-aged and irradiated mice. In co-cultures, irradiated brain endothelial cells induced the apoptosis of neural stem/progenitor cells via TGF-β/Smad3 signalling. Strikingly, the blockade of TGF-β signalling in vivo using a neutralizing antibody or the selective inhibitor SB-505124 significantly improved neurogenesis in aged and irradiated mice, prevented apoptosis and increased the proliferation of neural stem/progenitor cells. These findings suggest that anti-TGF-β-based therapy may be used for future interventions to prevent neurogenic collapse following radiotherapy or during aging. PMID:23526803

  17. Wnt Regulates Proliferation and Neurogenic Potential of Müller Glial Cells via a Lin28/let-7 miRNA-Dependent Pathway in Adult Mammalian Retinas.

    PubMed

    Yao, Kai; Qiu, Suo; Tian, Lin; Snider, William D; Flannery, John G; Schaffer, David V; Chen, Bo

    2016-09-27

    In cold-blooded vertebrates such as zebrafish, Müller glial cells (MGs) readily proliferate to replenish lost retinal neurons. In mammals, however, MGs lack regenerative capability as they do not spontaneously re-enter the cell cycle unless the retina is injured. Here, we show that gene transfer of β-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3β stabilizes β-catenin and activates MG proliferation. Downstream of Wnt, β-catenin binds to the Lin28 promoter and activates transcription. Deletion of Lin28 abolishes β-catenin-mediated effects on MG proliferation, and Lin28 gene transfer stimulates MG proliferation. We further demonstrate that let-7 miRNAs are critically involved in Wnt/Lin28-regulated MG proliferation. Intriguingly, a subset of cell-cycle-reactivated MGs express markers for amacrine cells. Together, these results reveal a key role of Wnt-Lin28-let7 miRNA signaling in regulating proliferation and neurogenic potential of MGs in the adult mammalian retina. PMID:27681429

  18. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

    PubMed

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  19. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

    PubMed

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  20. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    PubMed Central

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  1. Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support.

    PubMed

    Marshall, Gregory P; Deleyrolle, Loic P; Reynolds, Brent A; Steindler, Dennis A; Laywell, Eric D

    2014-01-01

    Microglia isolated from the neurogenic subependymal zone (SEZ) and hippocampus (HC) are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX) primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.

  2. Implications of irradiating the subventricular zone stem cell niche.

    PubMed

    Capilla-Gonzalez, Vivian; Bonsu, Janice M; Redmond, Kristin J; Garcia-Verdugo, Jose Manuel; Quiñones-Hinojosa, Alfredo

    2016-03-01

    Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs) reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.

  3. Introduction to Neurogenic Communication Disorders. Fifth Edition.

    ERIC Educational Resources Information Center

    Brookshire, Robert H.

    This book provides an overview of the causes and symptoms, and the typical courses, treatments, and outcomes of neurogenic communication disorders. Chapter 1 reviews the human nervous system and neurologic causes of adult communication disorders. Chapter 2 discusses the neurologic assessment and arriving at a diagnosis, including the neurologist's…

  4. The Jak-STAT target Chinmo prevents sex transformation of adult stem cells in the Drosophila testis niche

    PubMed Central

    Ma, Qing; Wawersik, Matthew; Matunis, Erika L.

    2014-01-01

    Local signals maintain adult stem cells in many tissues. Whether the sexual identity of adult stem cells must also be maintained was not known. In the adult Drosophila testis niche, local Jak-STAT signaling promotes somatic cyst stem cell (CySC) renewal through several effectors, including the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo). Here, we find that Chinmo also prevents feminization of CySCs. Chinmo promotes expression of the canonical male sex determination factor DoublesexM (DsxM) within CySCs and their progeny, and ectopic expression of DsxM in the CySC lineage partially rescues the chinmo sex transformation phenotype, placing Chinmo upstream of DsxM. The Dsx homologue DMRT1 prevents the male-to female conversion of differentiated somatic cells in the adult mammalian testis, but its regulation is not well understood. Our work indicates that sex maintenance occurs in adult somatic stem cells, and that this highly conserved process is governed by effectors of niche signals. PMID:25453558

  5. Mimicking Neural Stem Cell Niche by Biocompatible Substrates

    PubMed Central

    Regalado-Santiago, Citlalli; Juárez-Aguilar, Enrique; Olivares-Hernández, Juan David; Tamariz, Elisa

    2016-01-01

    Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to building in vitro models that include the relevant components of the in vivo niche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for the in vitro and in vivo mimicking of extracellular NSCs conditions. PMID:26880934

  6. Dynamic changes of the neurogenic potential in the rat cochlear nucleus during post-natal development.

    PubMed

    Rak, Kristen; Völker, Johannes; Frenz, Silke; Scherzed, Agmal; Radeloff, Andreas; Hagen, Rudolf; Mlynski, Robert

    2013-05-01

    Neuronal stem cells have been described in the post-natal cochlear nucleus recently. The aim of the study was to analyse the neurogenic potential in the cochlear nucleus from the early post-natal days until adulthood. Cochlear nuclei from Sprague-Dawley rats from post-natal day P3 up to P40 were examined. Neurosphere assays showed persistent neurosphere formation from the early post-natal days until adulthood. The numbers of generated neurospheres were fewer in older ages. Neurospheres were smaller, but displayed the same pattern of neuronal stem cell markers. The markers GFAP, MBP and ß-III Tubulin showed differentiation of dissociated cells from the neurospheres in all cells of the neuronal lineage. BrdU incorporation could be detected, in an age-dependent decrease, in whole-mount experiments of the cochlear nucleus on all examined days. BrdU co-labelled with Atoh1 and ß-III Tubulin. In addition, gene expression and cellular distribution studies of the neuronal stem cell markers displayed an age-dependent reduction in both quantity and numbers. The presented results display a possible neurogenic potential until adulthood in the cochlear nucleus by in vitro and in vivo experiments. The fact that this potential is highest at a critical period of development reveals possible functional importance for the development of the cochlear nucleus and the auditory function. The persistent neurogenic potential displayed until adulthood could be a neurogenic niche in the adult cochlear nucleus, which might be used for potential therapeutic strategies. PMID:23455726

  7. Adult feeding moths (Sphingidae) differ from non-adult feeding ones (Saturniidae) in activity-timing overlap and temporal niche width.

    PubMed

    de Camargo, Nícholas F; de Camargo, Willian R F; Corrêa, Danilo do C V; de Camargo, Amabílio J A; Vieira, Emerson M

    2016-02-01

    According to classic ecology, resource partitioning by segregation along at least one of the three main niche axes (time, food, and space) must take place for the coexistence of species with similar ecological requirements. We used nocturnal light traps to investigate the assemblage structuration of two moth families: Sphingidae (23 species) and Saturniidae (13 species). Because competition for food among adults potentially occurs only among sphingids, only for this family did we expect less overlap of diel activity patterns than expected by chance and also a greater temporal niche width compared to saturniids. Moreover, we expected a greater number of sphingid species pairs to differ in activity timing compared to saturniid pairs. We also hypothesized that in the case of a lack of temporal structuration, sphingids would be morphologically structured in relation to proboscis length. Contrary to what we expected, both families overlapped their activity patterns more than expected by chance alone and sphingid moths were not morphologically structured. Nevertheless, there were 173 significant pairwise differences in temporal activity between sphingids, contrasting with no interspecific differences between saturniids. Sphingid species also showed a wider temporal niche width than saturniids, as expected. Predation risk and abiotic factors may have caused the overall similarities in activity patterns for both families. The temporal niche seemed not to be determinant for the assemblage structuration of moths as a whole for either of the studied families, but segregation along the temporal niche axis of some potentially competing species pairs can be a relevant factor for the coexistence of nectar-feeding species.

  8. Immunological control of adult neural stem cells

    PubMed Central

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo; Garcia-Verdugo, Jose Manuel

    2010-01-01

    Adult neurogenesis occurs only in discrete regions of adult central nervous system: the subventricular zone and the subgranular zone. These areas are populated by adult neural stem cells (aNSC) that are regulated by a number of molecules and signaling pathways, which control their cell fate choices, survival and proliferation rates. For a long time, it was believed that the immune system did not exert any control on neural proliferative niches. However, it has been observed that many pathological and inflammatory conditions significantly affect NSC niches. Even more, increasing evidence indicates that chemokines and cytokines play an important role in regulating proliferation, cell fate choices, migration and survival of NSCs under physiological conditions. Hence, the immune system is emerging is an important regulator of neurogenic niches in the adult brain, which may have clinical relevance in several brain diseases. PMID:20861925

  9. Efficacy and Tolerability of Propiverine Hydrochloride in Patients With Neurogenic Detrusor Overactivity

    ClinicalTrials.gov

    2012-02-09

    Neurogenic Urinary Bladder Disorder; Urinary Bladder, Neurogenic; Bladder Disorder, Neurogenic; Urinary Bladder Disorder, Neurogenic; Neurogenic Bladder Disorder; Urinary Bladder Neurogenic Dysfunction; Urologic Diseases; Overactive Detrusor Function; Urinary Incontinence

  10. Neurogenic facial pain.

    PubMed

    Schott, G D

    1980-07-01

    Neurogenic facial pain can be classified as either paroxysmal or persistent. Trigeminal neuralgia is the commonest example of the former, and postherpetic neuralgia, atypical facial pain, and tension head and facial pains are examples of the latter. The cause of many of these pains is poorly understood, the complex neuroanatomy of the head and neck being a contributory factor. Even when the aetiology is known, the mechanism whereby pain is produced is usually obscure. While treatment with drugs and surgical measures for trigeminal neuralgia are often satisfactory, and acupuncture for pain due to "muscle tension" may be beneficial, there is often little effective treatment for a considerable proportion of patients with neurogenic facial pain. PMID:6943844

  11. Neurogenic muscle cramps.

    PubMed

    Katzberg, Hans D

    2015-08-01

    Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment. PMID:25673127

  12. Retroperitoneal neurogenous choristoma.

    PubMed

    Wan, J; Ritchey, M L; Muraszko, K; Bloom, D A

    1992-12-01

    A 6-year-old girl with urinary complaints underwent ultrasonography, which revealed a retroperitoneal cystic mass adjacent to the left kidney. Computerized tomography did not demonstrate whether the mass was an adrenal cyst or a duplicated upper pole segment. Exploration revealed a neurogenous choristoma, which is a collection of histologically normal tissue that is ectopically situated. We believe that this is the first report of this rare entity occurring in the retroperitoneum.

  13. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction.

  14. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    PubMed

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-09-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).

  15. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    PubMed

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-01-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2). PMID:27598108

  16. Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches.

    PubMed

    Giannakis, Marios; Stappenbeck, Thaddeus S; Mills, Jason C; Leip, Douglas G; Lovett, Michael; Clifton, Sandra W; Ippolito, Joseph E; Glasscock, Jarret I; Arumugam, Manimozhiyan; Brent, Michael R; Gordon, Jeffrey I

    2006-04-21

    We have sequenced 36,641 expressed sequence tags from laser capture microdissected adult mouse gastric and small intestinal epithelial progenitors, obtaining 4031 and 3324 unique transcripts, respectively. Using Gene Ontology (GO) terms, each data set was compared with cDNA libraries from intact adult stomach and small intestine. Genes in GO categories enriched in progenitors were filtered against genes in GO categories represented in hematopoietic, neural, and embryonic stem cell transcriptomes and mapped onto transcription factor networks, plus canonical signal transduction and metabolic pathways. Wnt/beta-catenin, phosphoinositide-3/Akt kinase, insulin-like growth factor-1, vascular endothelial growth factor, integrin, and gamma-aminobutyric acid receptor signaling cascades, plus glycerolipid, fatty acid, and amino acid metabolic pathways are among those prominently represented in adult gut progenitors. The results reveal shared as well as distinctive features of adult gut stem cells when compared with other stem cell populations.

  17. The Educational Software Marketplace and Adult Literacy Niches. Contractor Report, Adult Literacy and New Technologies: Tools for a Lifetime.

    ERIC Educational Resources Information Center

    Education Turnkey Systems, Inc., Falls Church, VA.

    Over the past 10 years computer technology has come to occupy a central place in American life and has caused a redefinition of the level of literacy skills needed to participate effectively in American society. At the same time, some 20 to 30 million adults have serious problems of basic literacy. Within this context, the Office of Technology…

  18. Augmentation cystoplasty in neurogenic bladder.

    PubMed

    Çetinel, Bülent; Kocjancic, Ervin; Demirdağ, Çetin

    2016-09-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  19. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  20. Artificial Stem Cell Niches

    PubMed Central

    Lutolf, Matthias P.; Blau, Helen M.

    2011-01-01

    Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such “artificial niches” constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. PMID:20882496

  1. Reawakening the sleeping beauty in the adult brain: neurogenesis from parenchymal glia.

    PubMed

    Péron, Sophie; Berninger, Benedikt

    2015-10-01

    Life-long neurogenesis is highly restricted to specialized niches in the adult mammalian brain and therefore the brain's capacity for spontaneous regeneration is extremely limited. However, recent work has demonstrated that under certain circumstances parenchymal astrocytes and NG2 glia can generate neuronal progeny. In the striatum, stroke or excitotoxic lesions can reawaken in astrocytes a latent neurogenic program resulting in the genesis of new neurons. By contrast, in brain areas that fail to mount a neurogenic response following injury, such as the cerebral cortex, forced expression of neurogenic reprogramming factors can lineage convert local glia into induced neurons. Yet, injury-induced and reprogramming-induced neurogenesis exhibit intriguing commonalities, suggesting that they may converge on similar mechanisms.

  2. Ecological niche

    SciTech Connect

    Shugart, H.H.

    1980-01-01

    The ecological niche of an organism is the set of environmental conditions under which the particular functions of the organism could be expected to assure its survival. It comprises both the set of conditions where the organism lives (often termed the habitat of the organism) and the functional role of the organism in the ecosystem. Recent works in niche theory have enabled ecologists to develop predictions and actual applications. The history of the niche concept, applications of niche theory, and ecological differences between similar species are discussed.

  3. Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions.

    PubMed

    Magnusson, Jens P; Frisén, Jonas

    2016-04-01

    In a few regions of the adult brain, specialized astrocytes act as neural stem cells capable of sustaining life-long neurogenesis. In other, typically non-neurogenic regions, some astrocytes have an intrinsic capacity to produce neurons when provoked by particular conditions but do not use this ability to replace neurons completely after injury or disease. Why do astrocytes display regional differences and why do they not use their neurogenic capacity for brain repair to a greater extent? In this Review, we discuss the neurogenic potential of astrocytes in different brain regions and ask what stimulates this potential in some regions but not in others. We discuss the transcriptional networks and environmental cues that govern cell identity, and consider how the activation of neurogenic properties in astrocytes can be understood as the de-repression of a latent neurogenic transcriptional program. PMID:27048686

  4. Radial glia and neural progenitors in the adult zebrafish central nervous system.

    PubMed

    Than-Trong, Emmanuel; Bally-Cuif, Laure

    2015-08-01

    The adult central nervous system (CNS) of the zebrafish, owing to its enrichment in constitutive neurogenic niches, is becoming an increasingly used model to address fundamental questions pertaining to adult neural stem cell (NSC) biology, adult neurogenesis and neuronal repair. Studies conducted in several CNS territories (notably the telencephalon, retina, midbrain, cerebellum and spinal cord) highlighted the presence, in these niches, of progenitor cells displaying NSC-like characters. While pointing to radial glial cells (RG) as major long-lasting, constitutively active and/or activatable progenitors in most domains, these studies also revealed a high heterogeneity in the progenitor subtypes used at the top of neurogenic hierarchies, including the persistence of neuroepithelial (NE) progenitors in some areas. Likewise, dissecting the molecular pathways underlying RG maintenance and recruitment under physiological conditions and upon repair in the zebrafish model revealed shared processes but also specific cascades triggering or sustaining reparative NSC recruitment. Together, the zebrafish adult brain reveals an extensive complexity of adult NSC niches, properties and control pathways, which extends existing understanding of adult NSC biology and gives access to novel mechanisms of efficient NSC maintenance and recruitment in an adult vertebrate brain. PMID:25976648

  5. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    PubMed Central

    2010-01-01

    Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs. PMID:20663133

  6. Neurogenic scapuloperoneal syndrome in childhood.

    PubMed Central

    Mercelis, R; Demeester, J; Martin, J J

    1980-01-01

    Two brothers presented with a slowly progressive scapuloperoneal syndrome starting in early childhood. Initially there were myopathic EMG changes, but these changed to those of denervation. Neuromuscular biopsies at an interval of five years confirmed the neurogenic character of the muscle atrophy. Images PMID:7441268

  7. The Neurogenic Factor NeuroD1 Is Expressed in Post-Mitotic Cells during Juvenile and Adult Xenopus Neurogenesis and Not in Progenitor or Radial Glial Cells

    PubMed Central

    D'Amico, Laure Anne; Boujard, Daniel; Coumailleau, Pascal

    2013-01-01

    In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU) or in situ hybridizations for cell type markers (Vimentin, Sox2). We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA-) cells and not radial glial (Vimentin+) or progenitors (Sox2+) cells. PMID:23799108

  8. Epidermal growth factor treatment of the adult brain subventricular zone leads to focal microglia/macrophage accumulation and angiogenesis.

    PubMed

    Lindberg, Olle R; Brederlau, Anke; Kuhn, H Georg

    2014-04-01

    One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  9. Secretion of Shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor

    PubMed Central

    Zhao, Hu; Feng, Jifan; Seidel, Kerstin; Shi, Songtao; Klein, Ophir; Sharpe, Paul; Chai, Yang

    2014-01-01

    Mesenchymal stem cells (MSCs) are typically defined by their in vitro characteristics, and as a consequence the in vivo identity of MSCs and their niches are poorly understood. To address this issue, we used lineage tracing in a mouse incisor model and identified the neurovascular bundle (NVB) as an MSC niche. We found that NVB sensory nerves secrete Shh protein, which activates Gli1 expression in periarterial cells that contribute to all mesenchymal derivatives. These periarterial cells do not express classical MSC markers used to define MSCs in vitro. In contrast, NG2+ pericytes represent an MSC subpopulation derived from Gli1+ cells; they express classical MSC markers and contribute little to homeostasis but are actively involved in injury repair. Likewise, incisor Gli1+ cells but not NG2+ cells exhibit typical MSC characteristics in vitro. Collectively, we demonstrate that MSCs originate from periarterial cells and are regulated by Shh secretion from a NVB. PMID:24506883

  10. Neurogenic dysphagia resulting from Chiari malformations.

    PubMed

    Pollack, I F; Pang, D; Kocoshis, S; Putnam, P

    1992-05-01

    Between 1980 and 1989, 15 of 46 patients (11 children, 4 adults) who underwent suboccipital craniectomy and cervical laminectomy for symptomatic Chiari malformations presented with manifestations of neurogenic dysphagia. Each of these patients had normal swallowing function before the development of dysphagic symptoms. Dysphagia was progressive in all 15 and, in most cases, preceded the onset of other severe brain stem signs. The rate of symptom progression varied depending on the age of the patient. Whereas the six infants (all Chiari II) deteriorated rapidly after the onset of initial symptoms, the five older children (two Chiari I, three Chiari II) and four adults (all Chiari I) showed a more gradual deterioration. In 11 patients with severe dysphagia, barium video esophagograms, pharyngoesophageal motility studies, continuous esophageal pH monitoring, and appropriate scintigraphic studies were useful in defining the scope of the swallowing impairment and determining whether perioperative nasogastric or gastrostomy feedings, gastric fundoplication, and/or tracheostomy were needed to maintain adequate nutrition and avoid aspiration. These patients all had widespread dysfunction of the swallowing mechanism, with a combination of diffuse pharyngoesophageal dysmotility, cricopharyngeal achalasia, nasal regurgitation, tracheal aspiration, and gastroesophageal reflux. The pathophysiology of these swallowing impairments and their relation to the hindbrain malformation is discussed. Postoperative outcome with regard to swallowing function correlated with the severity of preoperative symptoms. The four patients with mild dysphagia showed rapid improvement in swallowing function after surgery. Seven patients with more severe impairment but without other signs of severe brain stem compromise, such as central apnea or complete bilateral vocal cord paralysis, also improved, albeit more slowly. In contrast, the outcome in the four patients who developed other signs of severe

  11. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    PubMed

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive.

  12. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    PubMed

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive. PMID:17901404

  13. A possible role for the immune system in adult neurogenesis: new insights from an invertebrate model.

    PubMed

    Harzsch, Steffen; von Bohlen Und Halbach, Oliver

    2016-04-01

    Persistent neurogenesis in the adult brain of both vertebrates and invertebrates was previously considered to be driven by self-renewing neuronal stem cells of ectodermal origin. Recent findings in an invertebrate model challenge this view and instead provide evidence for a recruitment of neuronal precursors from a non-neuronal source. In the brain of adult crayfish, a neurogenic niche was identified that contributes progeny to the adult central olfactory pathway. The niche may function in attracting cells from the hemolymph and transforming them into cells with a neuronal fate. This finding implies that the first-generation neuronal precursors located in the crayfish neurogenic niche are not self-renewing. Evidence is summarized in support of a critical re-evaluation of long-term self-renewal of mammalian neuronal stem cells. Latest findings suggest that a tight link between the immune system and the system driving adult neurogenesis may not only exist in the crayfish but also in mammals. PMID:26739123

  14. Regional and Stage-Specific Effects of Prospectively Purified Vascular Cells on the Adult V-SVZ Neural Stem Cell Lineage

    PubMed Central

    Crouch, Elizabeth E.; Liu, Chang; Silva-Vargas, Violeta

    2015-01-01

    Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contribution of pericytes to the neural stem cell niche has not been defined. Here, we describe a rapid FACS purification strategy to simultaneously isolate primary endothelial cells and pericytes from brain microregions of nontransgenic mice using CD31 and CD13 as surface markers. We compared the effect of purified vascular cells from a neurogenic (V-SVZ) and non-neurogenic brain region (cortex) on the V-SVZ stem cell lineage in vitro. Endothelial and pericyte diffusible signals from both regions differentially promote the proliferation and neuronal differentiation of qNSCs, aNSCs, and TACs. Unexpectedly, diffusible cortical signals had the most potent effects on V-SVZ proliferation and neurogenesis, highlighting the intrinsic capacity of non-neurogenic vasculature to support stem cell behavior. Finally, we identify PlGF-2 as an endothelial-derived mitogen that promotes V-SVZ cell proliferation. This purification strategy provides a platform to define the functional and molecular contribution of vascular cells to stem cell niches and other brain regions under different physiological and pathological states. PMID:25788671

  15. Niche explosion.

    PubMed

    Normark, Benjamin B; Johnson, Norman A

    2011-05-01

    The following syndrome of features occurs in several groups of phytophagous insects: (1) wingless females, (2) dispersal by larvae, (3) woody hosts, (4) extreme polyphagy, (5) high abundance, resulting in status as economic pests, (6) invasiveness, and (7) obligate parthenogenesis in some populations. If extreme polyphagy is defined as feeding on 20 or more families of hostplants, this syndrome is found convergently in several species of bagworm moths, tussock moths, root weevils, and 5 families of scale insects. We hypothesize that extreme polyphagy in these taxa results from "niche explosion", a positive feedback loop connecting large population size to broad host range. The niche explosion has a demographic component (sometimes called the "amplification effect" in studies of pathogens) as well as a population-genetic component, due mainly to the increased effectiveness of natural selection in larger populations. The frequent origins of parthenogenesis in extreme polyphages are, in our interpretation, a consequence of this increased effectiveness of natural selection and consequent reduced importance of sexuality. The niche explosion hypothesis makes detailed predictions about the comparative genomics and population genetics of extreme polyphages and related specialists. It has a number of potentially important implications, including an explanation for the lack of observed trade-offs between generalists and specialists, a re-interpretation of the ecological correlates of parthenogenesis, and a general expectation that Malthusian population explosions may be amplified by Darwinian effects.

  16. Isolation, culture and analysis of adult subependymal neural stem cells.

    PubMed

    Belenguer, Germán; Domingo-Muelas, Ana; Ferrón, Sacri R; Morante-Redolat, José Manuel; Fariñas, Isabel

    2016-01-01

    Individual cells dissected from the subependymal neurogenic niche of the adult mouse brain proliferate in medium containing basic fibroblast growth factor (bFGF) and/or epidermal growth factor (EGF) as mitogens, to produce multipotent clonal aggregates called neurospheres. These cultures constitute a powerful tool for the study of neural stem cells (NSCs) provided that they allow the analysis of their features and potential capacity in a controlled environment that can be modulated and monitored more accurately than in vivo. Clonogenic and population analyses under mitogen addition or withdrawal allow the quantification of the self-renewing and multilineage potency of these cells and the identification of the mechanisms involved in these properties. Here, we describe a set of procedures developed and/or modified by our group including several experimental options that can be used either independently or in combination for the ex vivo assessment of cell properties of NSCs obtained from the adult subependymal niche. PMID:27016251

  17. Inhibition of Sox2 Expression in the Adult Neural Stem Cell Niche In Vivo by Monocationic-based siRNA Delivery

    PubMed Central

    Remaud, Sylvie; López-Juárez, Silvia Alejandra; Bolcato-Bellemin, Anne-Laure; Neuberg, Patrick; Stock, Fabrice; Bonnet, Marie-Elise; Ghaddab, Rym; Clerget-Froidevaux, Marie Stéphanie; Pierre-Simons, Jacqueline; Erbacher, Patrick; Demeneix, Barbara A; Morvan-Dubois, Ghislaine

    2013-01-01

    RNA interference (RNAi) is a major tool for basic and applied investigations. However, obtaining RNAi data that have physiological significance requires investigation of regulations and therapeutic strategies in appropriate in vivo settings. To examine in vivo gene regulation and protein function in the adult neural stem cell (NSC) niche, we optimized a new non-viral vector for delivery of siRNA into the subventricular zone (SVZ). This brain region contains the neural stem and progenitor cells populations that express the stem cell marker, SOX2. Temporally and spatially controlled Sox2 knockdown was achieved using the monocationic lipid vector, IC10. siRNA/IC10 complexes were stable over time and smaller (<40 nm) than jetSi complexes (≈400 nm). Immunocytochemistry showed that siRNA/IC10 complexes efficiently target both the progenitor and stem cell populations in the adult SVZ. Injection of the complexes into the lateral brain ventricle resulted in specific knockdown of Sox2 in the SVZ. Furthermore, IC10-mediated transient in vivo knockdown of Sox2-modulated expression of several genes implicated in NSC maintenance. Taken together, these data show that IC10 cationic lipid formulation can efficiently vectorize siRNA in a specific area of the adult mouse brain, achieving spatially and temporally defined loss of function. PMID:23612115

  18. Inhibition of Sox2 Expression in the Adult Neural Stem Cell Niche In Vivo by Monocationic-based siRNA Delivery.

    PubMed

    Remaud, Sylvie; López-Juárez, Silvia Alejandra; Bolcato-Bellemin, Anne-Laure; Neuberg, Patrick; Stock, Fabrice; Bonnet, Marie-Elise; Ghaddab, Rym; Clerget-Froidevaux, Marie Stéphanie; Pierre-Simons, Jacqueline; Erbacher, Patrick; Demeneix, Barbara A; Morvan-Dubois, Ghislaine

    2013-04-23

    RNA interference (RNAi) is a major tool for basic and applied investigations. However, obtaining RNAi data that have physiological significance requires investigation of regulations and therapeutic strategies in appropriate in vivo settings. To examine in vivo gene regulation and protein function in the adult neural stem cell (NSC) niche, we optimized a new non-viral vector for delivery of siRNA into the subventricular zone (SVZ). This brain region contains the neural stem and progenitor cells populations that express the stem cell marker, SOX2. Temporally and spatially controlled Sox2 knockdown was achieved using the monocationic lipid vector, IC10. siRNA/IC10 complexes were stable over time and smaller (<40 nm) than jetSi complexes (≈400 nm). Immunocytochemistry showed that siRNA/IC10 complexes efficiently target both the progenitor and stem cell populations in the adult SVZ. Injection of the complexes into the lateral brain ventricle resulted in specific knockdown of Sox2 in the SVZ. Furthermore, IC10-mediated transient in vivo knockdown of Sox2-modulated expression of several genes implicated in NSC maintenance. Taken together, these data show that IC10 cationic lipid formulation can efficiently vectorize siRNA in a specific area of the adult mouse brain, achieving spatially and temporally defined loss of function.Molecular Therapy-Nucleic Acids (2013) 2, e89; doi:10.1038/mtna.2013.8; published online 23 April 2013.

  19. Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner

    PubMed Central

    Hornsby, Amanda K.E.; Redhead, Yushi T.; Rees, Daniel J.; Ratcliff, Michael S.G.; Reichenbach, Alex; Wells, Timothy; Francis, Lewis; Amstalden, Katia; Andrews, Zane B.; Davies, Jeffrey S.

    2016-01-01

    The beneficial effects of calorie restriction (CR) have been described at both organismal and cellular levels in multiple organs. However, our understanding of the causal mediators of such hormesis is poorly understood, particularly in the context of higher brain function. Here, we show that the receptor for the orexigenic hormone acyl-ghrelin, the growth hormone secretagogue receptor (Ghsr), is enriched in the neurogenic niche of the hippocampal dentate gyrus (DG). Acute elevation of acyl-ghrelin levels by injection or by overnight CR, increased DG levels of the neurogenic transcription factor, Egr-1. Two weeks of CR increased the subsequent number of mature newborn neurons in the DG of adult wild-type but not Ghsr−/− mice. CR wild-type mice also showed improved remote contextual fear memory. Our findings suggest that Ghsr mediates the beneficial effects of CR on enhancing adult hippocampal neurogenesis and memory. PMID:26460782

  20. Alcohol and adult hippocampal neurogenesis: promiscuous drug, wanton effects.

    PubMed

    Geil, Chelsea R; Hayes, Dayna M; McClain, Justin A; Liput, Daniel J; Marshall, S Alex; Chen, Kevin Y; Nixon, Kimberly

    2014-10-01

    Adult neurogenesis is now widely accepted as an important contributor to hippocampal integrity and function but also dysfunction when adult neurogenesis is affected in neuropsychiatric diseases such as alcohol use disorders. Excessive alcohol consumption, the defining characteristic of alcohol use disorders, results in a variety of cognitive and behavioral impairments related wholly or in part to hippocampal structure and function. Recent preclinical work has shown that adult neurogenesis may be one route by which alcohol produces hippocampal neuropathology. Alcohol is a pharmacologically promiscuous drug capable of interfering with adult neurogenesis through multiple mechanisms. This review will discuss the primary mechanisms underlying alcohol-induced changes in adult hippocampal neurogenesis including alcohol's effects on neurotransmitters, CREB and its downstream effectors, and the neurogenic niche.

  1. Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement.

    PubMed

    Rawicki, B; Sheean, G; Fung, V S C; Goldsmith, S; Morgan, C; Novak, I

    2010-08-01

    Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications.

  2. Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement.

    PubMed

    Rawicki, B; Sheean, G; Fung, V S C; Goldsmith, S; Morgan, C; Novak, I

    2010-08-01

    Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications. PMID:20633183

  3. Understanding migraine: Potential role of neurogenic inflammation.

    PubMed

    Malhotra, Rakesh

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment

  4. Understanding migraine: Potential role of neurogenic inflammation

    PubMed Central

    Malhotra, Rakesh

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment

  5. Droxidopa in neurogenic orthostatic hypotension.

    PubMed

    Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

    2015-01-01

    Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy (MSA), pure autonomic failure (PAF), and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

  6. Droxidopa in neurogenic orthostatic hypotension

    PubMed Central

    Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

    2015-01-01

    Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy, pure autonomic failure and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise blood pressure by acting at the neurovascular junction to increase vascular tone. This review summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

  7. Management of neurogenic orthostatic hypotension.

    PubMed

    Arbique, Debbie; Cheek, Dennis; Welliver, Mark; Vongpatanasin, Wanpen

    2014-04-01

    The burden of orthostatic hypotension (OH) on public health is a universally recognized enigmatic clinical condition that is associated with significant increases on morbidity and mortality rates, and can take a major toll on one's quality of life. Orthostatic hypotension is predictive of vascular deaths from acute myocardial infarction, strokes in the middle aged population, and increases mortality rates when associated with diabetes, hypertension, Parkinson's disease, and patients receiving renal dialysis. The consensus definition for OH is a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 minutes of quiet standing. Because neurogenic OH is often accompanied by supine hypertension, the treatment program should aim toward minimizing OH and the potential fall injuries related to cerebral hypoperfusion without exacerbating nocturnal hypertension that may lead to excessive cardiovascular complications.

  8. Botulinum Toxin in Neurogenic Detrusor Overactivity

    PubMed Central

    Ferreira, Rúiter Silva; Rassi, Mauricio Carneiro

    2012-01-01

    Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks) and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life. PMID:23094220

  9. Neurogenic differentiation of amniotic fluid stem cells.

    PubMed

    Rosner, M; Mikula, M; Preitschopf, A; Feichtinger, M; Schipany, K; Hengstschläger, M

    2012-05-01

    In 2003, human amniotic fluid has been shown to contain stem cells expressing Oct-4, a marker for pluripotency. This finding initiated a rapidly growing and very promising new stem cell research field. Since then, amniotic fluid stem (AFS) cells have been demonstrated to harbour the potential to differentiate into any of the three germ layers and to form three-dimensional aggregates, so-called embryoid bodies, known as the principal step in the differentiation of pluripotent stem cells. Marker selection and minimal dilution approaches allow the establishment of monoclonal AFS cell lineages with high proliferation potential. AFS cells have a lower risk for tumour development and do not raise the ethical issues of embryonic stem cells. Compared to induced pluripotent stem cells, AFS cells do not need exogenic treatment to induce pluripotency, are chromosomal stable and do not harbour the epigenetic memory and accumulated somatic mutations of specific differentiated source cells. Compared to adult stem cells, AFS can be grown in larger quantities and show higher differentiation potential. Accordingly, in the recent past, AFS became increasingly accepted as an optimal tool for basic research and probably also for specific cell-based therapies. Here, we review the current knowledge on the neurogenic differentiation potential of AFS cells.

  10. Neurogenic inflammation and sensitivity to environmental chemicals.

    PubMed

    Meggs, W J

    1993-08-01

    Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities.

  11. Neuronal fate determinants of adult olfactory bulb neurogenesis.

    PubMed

    Hack, Michael A; Saghatelyan, Armen; de Chevigny, Antoine; Pfeifer, Alexander; Ashery-Padan, Ruth; Lledo, Pierre-Marie; Götz, Magdalena

    2005-07-01

    Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.

  12. The "bends" and neurogenic bladder dysfunction.

    PubMed

    Elliott, D S; Mutchnik, S; Boone, T B

    2001-02-01

    Decompression sickness (the "bends") is a well-known risk of scuba diving. The pathophysiology and treatment is well documented. In the urologic data, no reference to the development of a neurogenic bladder as a result of an episode of the bends was found. We present the evaluation and management of a previously asymptomatic man who developed detrusor hyperreflexia after an episode of decompression sickness. Urologists in coastal communities should be aware of the potential risk of the development of neurogenic bladder.

  13. The Cell as the First Niche Construction.

    PubMed

    Torday, John S

    2016-01-01

    Niche construction nominally describes how organisms can form their own environments, increasing their capacity to adapt to their surroundings. It is hypothesized that the formation of the first cell as 'internal' Niche Construction was the foundation for life, and that subsequent niche constructions were iterative exaptations of that event. The first instantation of niche construction has been faithfully adhered to by returning to the unicellular state, suggesting that the life cycle is zygote to zygote, not adult to adult as is commonly held. The consequent interactions between niche construction and epigenetic inheritance provide a highly robust, interactive, mechanistic way of thinking about evolution being determined by initial conditions rather than merely by chance mutation and selection. This novel perspective offers an opportunity to reappraise the processes involved in evolution mechanistically, allowing for scientifically testable hypotheses rather than relying on metaphors, dogma, teleology and tautology. PMID:27136594

  14. The Cell as the First Niche Construction

    PubMed Central

    Torday, John S.

    2016-01-01

    Niche construction nominally describes how organisms can form their own environments, increasing their capacity to adapt to their surroundings. It is hypothesized that the formation of the first cell as ‘internal’ Niche Construction was the foundation for life, and that subsequent niche constructions were iterative exaptations of that event. The first instantation of niche construction has been faithfully adhered to by returning to the unicellular state, suggesting that the life cycle is zygote to zygote, not adult to adult as is commonly held. The consequent interactions between niche construction and epigenetic inheritance provide a highly robust, interactive, mechanistic way of thinking about evolution being determined by initial conditions rather than merely by chance mutation and selection. This novel perspective offers an opportunity to reappraise the processes involved in evolution mechanistically, allowing for scientifically testable hypotheses rather than relying on metaphors, dogma, teleology and tautology. PMID:27136594

  15. The Cell as the First Niche Construction.

    PubMed

    Torday, John S

    2016-04-28

    Niche construction nominally describes how organisms can form their own environments, increasing their capacity to adapt to their surroundings. It is hypothesized that the formation of the first cell as 'internal' Niche Construction was the foundation for life, and that subsequent niche constructions were iterative exaptations of that event. The first instantation of niche construction has been faithfully adhered to by returning to the unicellular state, suggesting that the life cycle is zygote to zygote, not adult to adult as is commonly held. The consequent interactions between niche construction and epigenetic inheritance provide a highly robust, interactive, mechanistic way of thinking about evolution being determined by initial conditions rather than merely by chance mutation and selection. This novel perspective offers an opportunity to reappraise the processes involved in evolution mechanistically, allowing for scientifically testable hypotheses rather than relying on metaphors, dogma, teleology and tautology.

  16. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  17. The stem cell niches in bone

    PubMed Central

    Yin, Tong; Li, Linheng

    2006-01-01

    The stem cell niche is composed of a specialized population of cells that plays an essential role in regulating adult stem cell self-renewal and differentiation. In adults, osteoblasts, responsible for osteogenesis, and hematopoietic cells, responsible for hematopoiesis, are closely associated in the bone marrow, suggesting a reciprocal relationship between the two. It was recently discovered that a subset of osteoblasts functions as a key component of the HSC niche (namely, the osteoblastic niche), controlling HSC numbers. HSCs interact not only with osteoblasts but also with other stromal cells, including endothelial cells. Sinusoidal endothelial cells in bone marrow have been revealed as an alternative HSC niche called the vascular niche. In this Review we compare the architecture of these 2 HSC niches in bone marrow. We also highlight the function of osteoblasts in maintaining a quiescent HSC microenvironment and the likely role of the vascular niche in regulating stem cell proliferation, differentiation, and mobilization. In addition, we focus on studies of animal models and in vitro assays that have provided direct insights into the actions of these osteoblastic and vascular niches, revealing central roles for numerous signaling and adhesion molecules. Many of the discoveries described herein may contribute to future clinical treatments for hematopoietic and bone-related disorders, including cancer. PMID:16670760

  18. Neurogenic inflammation in lung disease: burnt out?

    PubMed

    Rogers, D F

    1997-01-01

    Neurogenic inflammation results from activation of sensory nerves which, acting in an 'efferent' manner, release sensory neuropeptides to induce a wide variety of physiological and immunological responses. This process is easy to demonstrate experimentally in the airways of small laboratory animal species but in human airways is equivocal and, at best, minor compared with cholinergic neural control. Nevertheless, sensory neuropeptides (calcitonin gene-related peptide and the tachykinins, substance P and neurokinin A) induce airway responses in both laboratory animals and humans which suggest a potential for sensory-efferent control of human airways. In addition, there is indirect evidence for an increased 'expression' of sensory nerves and tachykinin receptors in asthma and bronchitis, which indicates that neurogenic inflammation contributes to pathophysiology of these airway conditions. In contrast, clinical trials using different classes of drugs to inhibit sensory nerve responses have failed to resolve whether neurogenic inflammation is involved in asthma, although there are concerns about the relevance of some of these studies. In contrast to their involvement in airway neurogenic inflammation, sensory nerves may be important in initiating protective reflexes, including coughing and sneezing, acting via their afferent pathways. Thus, although flickering, the concept of neurogenic inflammation in lung disease is not yet burnt out. However, it needs the rekindling of interest which re-evaluation as a protective process may bring, together with data from more appropriate clinical studies in asthma and chronic bronchitis. PMID:17657611

  19. Neurogenic muscle hypertrophy: a case report

    PubMed Central

    Shin, Hyun Ho; Jeon, Young Hoon; Jang, Seung Won

    2016-01-01

    Muscular hypertrophy is caused mainly due to myopathic disorder. But, it is also rarely produced by neurogenic disorder. A 74-year-old woman complained of right calf pain with hypertrophy for several years. Recent lumbar spine magnetic resonance imaging (MRI) showed central and lateral canal narrowing at the L4-L5 intervertebral space. Lower extremity MRI revealed fatty change of right medial head of the gastrocnemius and soleus, causing right calf hypertrophy. Electrodiagnostic examinations including electromyography and nerve conduction velocity testing demonstrated 5th lumbar and 1st sacral polyradiculopathy. Integrating all the results, the diagnosis was neurogenic muscle hypertrophy. Neurogenic muscle hypertrophy is very rare, but we recommend that clinicians consider this problem when a patient complains of lower limb hypertrophy and pain. PMID:27738507

  20. Neurogenic vascular headaches, food and chemical triggers.

    PubMed

    Trotsky, M B

    1994-04-01

    Recent evidence has demonstrated that neurogenic vascular headaches are a combination of neurological primary events and secondary vasomotor changes. The neurological events involve the hypothalamus and sensory cortex with sympathetic hypofunction and noradrenergic abnormalities. A platelet theory has been proposed but has not really been confirmed as a legitimate cause of the neurogenic vascular headaches. Food and chemicals in foods can act as a precipitating factor in the food-sensitive neurogenic vascular headache patient. In these patients evidence is now being demonstrated to confirm this, but larger patient studies are needed. The food-sensitive migraine patient and cluster headache patient must give a good history and food diary to go along with active challenges and provocative testing in order to determine the causative foods. Any concomitant allergies of inhalants or environmentals must also be treated. The treatment modalities of elimination and rotation diets or provocation neutralization may successfully control the headaches without the need for continuous medications.

  1. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium.

    PubMed

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S

    2016-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Finally, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients.

  2. Analysis of carbonated thin liquids in pediatric neurogenic dysphagia

    PubMed Central

    Lundine, Jennifer P.; Bates, David G.; Yin, Han

    2015-01-01

    Background Aspiration of liquids is a serious complication of neurological impairments such as traumatic brain injury or stroke. Carbonated liquids have been examined as a possible alternative to thickened liquids to help reduce aspiration in cases of dysphagia in adults, but no published literature to the best of our knowledge has evaluated this technique in children. If carbonated liquids result in safer swallowing in children, they could provide a preferred alternative to thickened liquids. Objective This pilot study examined whether carbonated thin liquids (CARB) improved swallowing compared to noncarbonated thin liquids (NOCARB) for children with neurogenic dysphagia. Materials and methods Twenty-four children admitted to a level I trauma center for acute neurological injury/disease were evaluated via videofluoroscopic swallow studies. Four descriptive outcome measures were contrasted. Results CARB significantly decreased pooling (P=0.0006), laryngeal penetration/aspiration (P=0.0044) and Penetration-Aspiration Scale scores (P=0.0127) when compared to NOCARB. On average, CARB improved scores on the Penetration-Aspiration Scale by 3.7 points for participants who aspirated NOCARB. There was no significant difference in pharyngeal residue noted between CARB and NOCARB (P=0.0625). Conclusion These findings support the hypothesis that carbonated thin liquids may provide an alternative to thickened liquids for children with neurogenic dysphagia. Implications for future research and clinical practice are discussed. PMID:25758792

  3. Regulation of hematopoietic stem cells in the niche.

    PubMed

    Zhao, Meng; Li, LinHeng

    2015-12-01

    Hematopoiesis provides a suitable model for understanding adult stem cells and their niche. Hematopoietic stem cells (HSCs) continuously produce blood cells through orchestrated proliferation, self-renewal, and differentiation in the bone marrow (BM). Within the BM exists a highly organized microenvironment termed "niche" where stem cells reside and are maintained. HSC niche is the first evidence that a microenvironment contributes to protecting stem cell integrity and functionality in mammals. Although multiple models exist, recent progress has principally elucidated the cellular complexity of the HSC niche that maintains and regulates HSCs in BM. Here we introduce the development and summarize the achievements of HSC niche studies.

  4. Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system

    PubMed Central

    Jiao, Jian-wei; Feldheim, David A.; Chen, Dong Feng

    2008-01-01

    In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report that astrocytes in areas outside of the SGZ and SVZ of adult mice express high levels of ephrin-A2 and -A3, which present an inhibitory niche, negatively regulating neural progenitor cell growth. Adult mice lacking both ephrin-A2 and -A3 display active ongoing neurogenesis throughout the CNS. These findings suggest that neural cell replacement therapies for neurodegeneration or injury in the adult CNS may be achieved by manipulating ephrin signaling pathways. PMID:18562299

  5. Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH) neurons

    PubMed Central

    Cortés-Campos, Christian; Letelier, Joaquín; Ceriani, Ricardo; Whitlock, Kathleen E.

    2015-01-01

    ABSTRACT Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons. PMID:26209533

  6. Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

    PubMed Central

    Richardson, Richard B

    2011-01-01

    Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. PMID:21204614

  7. The neurogenic bladder: introducing four contributions.

    PubMed

    Proesmans, Willem

    2008-04-01

    Neurogenic bladder dysfunction in children is frequently seen in patients with meningomyelocele (MMC). The disorder carries a high risk for all kinds of complications, with renal damage being the most important. More than 95% of MMC patients have a neurogenic bladder, the paramount manifestation of which is a disturbed coordination between detrusor and sphincter muscles. This vesicourethral dysfunction leads to defective filling and emptying of the urinary bladder. Voiding at will is almost never possible. According to the location and extent of the neural tube lesion, patients have either an atonic or a hypertonic pelvic floor and either an atonic or a hypertonic detrusor, leading to four classic combinations. Hypertonic sphincter and detrusor hyperactivity lead to the most dangerous form of neurogenic bladder, referred to as the "unsafe" bladder. The presence of residual urine in a high-pressure container causes either decompensation of the detrusor with vesicoureteral reflux or deterioration of the bladder wall with hypertrophy and stiffness resulting in uterovesical obstruction. The subsequent insufficient drainage of the upper urinary tract leads to decompensation of the ureters and finally to chronic renal disease, the process being accelerated by urinary tract infections. The aim of treatment is to restore as much as possible both essential functions: urine storage and timely emptying of the reservoir. What should and can be achieved is a more or less adequate, low-pressure, functional capacity of the bladder that is emptied as completely as possible by clean intermittent catheterization (CIC). MMC leads to the prototype of neurogenic bladder in childhood. What we know and what we do for MMC patients can roughly be applied to all other forms of neurogenic bladder, either congenital or acquired.

  8. Fractone-heparan sulfates mediate BMP-7 inhibition of cell proliferation in the adult subventricular zone.

    PubMed

    Douet, Vanessa; Arikawa-Hirasawa, Eri; Mercier, Frederic

    2012-10-24

    Bone morphogenetic protein-7 (BMP-7) is a heparin-binding growth factor that inhibits cell proliferation in the subventricular zone (SVZ) of the lateral ventricle, the primary neurogenic niche in the adult brain. However, the physiological mechanisms regulating the activity of BMP-7 in the SVZ are unknown. Here, we report the inhibitory effect of BMP-7 on cell proliferation through the anterior SVZ after intracerebroventricular injection in the adult mouse. To determine whether the inhibition of cell proliferation induced by BMP-7 is dependant on heparin-binding, heparitinase-1 was intracerebroventricularly injected to N-desulfate heparan sulfate proteoglycans before BMP-7 was injected. Heparatinase-1 drastically reduced the inhibitory effect of BMP-7 on cell proliferation in the SVZ. To determine where BMP-7 binds within the niche, we visualized biotinylated-BMP-7 after intracerebroventricular injection, using streptavidin Texas red on frozen brain sections. BMP-7 binding was seen as puncta in the SVZ at the location of fractones, the particulate specialized extracellular matrix of the SVZ, which have been identified primarily by N-sulfated heparan sulfate immunoreactivity (NS-HS+). BMP binding was also seen in NS-HS+ blood vessels of the SVZ. Injection of heparitinase-1 prior to biotinylated BMP-7 resulted in the absence of signal for biotinylated-BMP-7 in the fractones and blood vessels, indicating that the binding is heparan sulfate dependant. These results indicate that BMP-7 requires heparan sulfates to bind and inhibit cell proliferation in the SVZ neurogenic niche. Heparan sulfates concentrated in fractones and SVZ blood vessels emerge as a functional stem cell niche component involved in growth factor activity.

  9. Neurogenic muscle involvement in myasthenia gravis

    PubMed Central

    Oosterhuis, Hans; Bethlem, Jaap

    1973-01-01

    An investigation was made into the occurrence of muscular atrophy and muscular pathology in a series of 170 patients with myasthenia gravis. The results can be summarized as follows: (1) Of the 148 patients with generalized myasthenia gravis, 14 showed local muscular atrophies. Of 10 biopsies from atrophic muscles, eight showed neurogenic changes, with or without lymphocytic infiltrations. One biopsy showed lymphocytic infiltrations only, and one showed type II-fibre atrophy (Table 1). No relationship was demonstrable between the presence of clilnical muscular atrophy and age, sex, duration of the disease, severity of the disease, presence of a thymoma, or drug resistant ophthalmoplegia. (2) In this group of patients 61 biopsies were examined from 46 individuals; 40 of these biopsies were taken from the quadriceps muscle. A thymoma was present in 17 patients. Examination disclosed neurogenic changes in 17 biopsies, lymphocytic infiltrates in 21, and myositis in one biopsy (Table 2). A distinct correlation was established between the presence of a thymoma and lymphocytic infiltrates, but none was demonstrable between thymoma and neurogenic changes (Table 3). (3) An enzyme-histochemical study was carried out in 35 cases, including 12 with neurogenic changes. A normal differentiation of type I- and type II-fibres was observed in eight instances, type grouping of type II-fibres in three, and type II-fibre atrophy in two cases. (4) In 21 patients and 19 controls, the smallest mean diameter was determined in the quadriceps muscle. Both type I- and type II-fibres proved to have a smaller mean diameter in the female patients than in the controls. In the male patients this could not be proven. (5) Of the eight patients who had died without disorders of ventilation, 90 muscle specimens were examined postmortem. Four of these patients had a thymoma. Lymphocytic infiltrations, found in 32 biopsy specimens, were mostly observed in the presence of a thymoma. Neurogenic changes

  10. Botulinum Toxin to Treat Neurogenic Bladder.

    PubMed

    Smith, Christopher P; Chancellor, Michael B

    2016-02-01

    Alteration in neural control from suprapontine areas to the nerves innervating the bladder can lead to bladder dysfunction and the development of a neurogenic bladder (NGB). Patients with NGB often suffer from urinary incontinence, which can lead to adverse events such as urinary tract infections and decubiti, in addition to creating a large care burden for family members or healthcare providers and significantly impairing patient quality of life. The common failure of anticholinergic medications has spurned the development of second-line treatments, including the use of botulinum toxin. OnabotulinumtoxinA (onaBoNT-A; BOTOX, Allergan, Inc.) was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat neurogenic detrusor overactivity in patients with urinary incontinence resulting from a NGB. In this review the authors summarize pertinent results from key trials leading to FDA approval of onaBoNT-A as well as more recent long-term data.

  11. UTIs in patients with neurogenic bladder.

    PubMed

    Jahromi, Mona S; Mure, Amanda; Gomez, Christopher S

    2014-09-01

    Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy. PMID:25113150

  12. Infantile amnesia: a neurogenic hypothesis.

    PubMed

    Josselyn, Sheena A; Frankland, Paul W

    2012-08-16

    In the late 19th Century, Sigmund Freud described the phenomenon in which people are unable to recall events from early childhood as infantile amnesia. Although universally observed, infantile amnesia is a paradox; adults have surprisingly few memories of early childhood despite the seemingly exuberant learning capacity of young children. How can these findings be reconciled? The mechanisms underlying this form of amnesia are the subject of much debate. Psychological/cognitive theories assert that the ability to maintain detailed, declarative-like memories in the long term correlates with the development of language, theory of mind, and/or sense of "self." However, the finding that experimental animals also show infantile amnesia suggests that this phenomenon cannot be explained fully in purely human terms. Biological explanations of infantile amnesia suggest that protracted postnatal development of key brain regions important for memory interferes with stable long-term memory storage, yet they do not clearly specify which particular aspects of brain maturation are causally related to infantile amnesia. Here, we propose a hypothesis of infantile amnesia that focuses on one specific aspect of postnatal brain development--the continued addition of new neurons to the hippocampus. Infants (humans, nonhuman primates, and rodents) exhibit high levels of hippocampal neurogenesis and an inability to form lasting memories. Interestingly, the decline of postnatal neurogenesis levels corresponds to the emergence of the ability to form stable long-term memory. We propose that high neurogenesis levels negatively regulate the ability to form enduring memories, most likely by replacing synaptic connections in preexisting hippocampal memory circuits.

  13. Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications.

    PubMed

    Kuwabara, Tomoko; Asashima, Makoto

    2012-06-01

    Neural stem cells (NSCs), which are responsible for continuous neurogenesis during the adult stage, are present in human adults. The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb. Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient. Through the combined influence of extrinsic cues and innate programming, adult neurogenesis is a finely regulated process occurring in a specialized cellular environment, a niche. Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood, but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments. Diabetes is a devastating disease affecting more than 200 million people worldwide. Numerous diabetic patients suffer increased symptom severity after the onset, involving complications such as retinopathy and nephropathy. Therefore, the development of treatments for fundamental diabetes is important. The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function, reducing future risks while also providing a long-term cure. Here, we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure, and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

  14. Urinary Tract Infection and Neurogenic Bladder.

    PubMed

    McKibben, Maxim J; Seed, Patrick; Ross, Sherry S; Borawski, Kristy M

    2015-11-01

    Urinary tract infections (UTIs) are frequent, recurrent, and lifelong for patients with neurogenic bladder and present challenges in diagnosis and treatment. Patients often present without classic symptoms of UTI but with abdominal or back pain, increased spasticity, and urinary incontinence. Failure to recognize and treat infections can quickly lead to life-threatening autonomic dysreflexia or sepsis, whereas overtreatment contributes to antibiotic resistance, thus limiting future treatment options. Multiple prevention methods are used but evidence-based practices are few. Prevention and treatment of symptomatic UTI requires a multimodal approach that focuses on bladder management as well as accurate diagnosis and appropriate antibiotic treatment. PMID:26475949

  15. Companion Blood Cells Control Ovarian Stem Cell Niche Microenvironment and Homeostasis.

    PubMed

    Van De Bor, Véronique; Zimniak, Geordie; Papone, Lise; Cerezo, Delphine; Malbouyres, Marilyne; Juan, Thomas; Ruggiero, Florence; Noselli, Stéphane

    2015-10-20

    The extracellular matrix plays an essential role for stem cell differentiation and niche homeostasis. Yet, the origin and mechanism of assembly of the stem cell niche microenvironment remain poorly characterized. Here, we uncover an association between the niche and blood cells, leading to the formation of the Drosophila ovarian germline stem cell niche basement membrane. We identify a distinct pool of plasmatocytes tightly associated with the developing ovaries from larval stages onward. Expressing tagged collagen IV tissue specifically, we show that the germline stem cell niche basement membrane is produced by these "companion plasmatocytes" in the larval gonad and persists throughout adulthood, including the reproductive period. Eliminating companion plasmatocytes or specifically blocking their collagen IV expression during larval stages results in abnormal adult niches with excess stem cells, a phenotype due to aberrant BMP signaling. Thus, local interactions between the niche and blood cells during gonad development are essential for adult germline stem cell niche microenvironment assembly and homeostasis.

  16. Role of astrocytes as neural stem cells in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo

    2012-01-01

    In the adult mammalian brain, bona fide neural stem cells were discovered in the subventricular zone (SVZ), the largest neurogenic niche lining the striatal wall of the lateral ventricles of the brain. In this region resides a subpopulation of astrocytes that express the glial fibrillary acidic protein (GFAP), nestin and LeX. Astonishingly, these GFAP-expressing progenitors display stem-cell-like features both in vivo and in vitro. Throughout life SVZ astrocytes give rise to interneurons and oligodendrocyte precursors, which populate the olfactory bulb and the white matter, respectively. The role of the progenies of SVZ astrocytes has not been fully elucidated, but some evidence indicates that the new neurons play a role in olfactory discrimination, whereas oligodendrocytes contribute to myelinate white matter tracts. In this chapter, we describe the astrocytic nature of adult neural stem cells, their organization into the SVZ and some of their molecular and genetic characteristics. PMID:23619383

  17. The neurogenic competence of progenitors from the postnatal rat retina in vitro.

    PubMed

    Engelhardt, Maren; Wachs, Frank-Peter; Couillard-Despres, Sebastien; Aigner, Ludwig

    2004-05-01

    The mammalian retina develops from stem or progenitor cells that are of neuroectodermal origin and derive from bilateral invaginations of the neuroepithelium, the optic vesicles. Shortly after birth, around 12 days postnatal in rats, the retina is fully developed in its cellular parts. Even though different cell types in the adult might be potential sources for retinal stem cells or progenitor cells, the retina is a non-neurogenic region and the diseased retina is devoid of any spontaneous regeneration. In an attempt to link late developmental processes to the adult situation, we analyzed the presence and the neurogenic potential of retinal progenitors during the postnatal period and compared it to adult ciliary body (CB) derived retinal progenitors and subventricular zone (SVZ) derived neural stem cells. Retinal progenitor properties were identified by the capacity to proliferate and by the expression of the progenitor markers Nestin, Flk-1, Chx10, Pax6 and the radial glia marker BLBP. The neurogenic potential was assayed by the expression of the neuronal markers doublecortin, betaIII Tubulin, Map2 and NSE, the glial makers A2B5, NG2, GalC and GFAP, and by incorporation of BrdU. The number of Flk-1 positive cells and concomitantly the number of newly born betaIII Tubulin-positive cells decreased within the first postnatal week in retinal progenitor cultures and no newly generated betaIII Tubulin, but GFAP positive cells were detected thereafter. In contrast to neural stem cells derived from the adult SVZ, postnatal and adult CB derived progenitors had a lower and a restricted proliferation potential and did not generate oligodendrocytes. The work demonstrates, however, that the existence of retinal progenitor cells is not restricted to embryonic development. In the sensory retina the differentiation potential of late retinal progenitors becomes restricted to the glial lineage, whereas neurogenic progenitor cells are still present in the CB. In addition, major

  18. Neurogenic bladder in spinal cord injury patients

    PubMed Central

    Taweel, Waleed Al; Seyam, Raouf

    2015-01-01

    Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

  19. Runaway cultural niche construction.

    PubMed

    Rendell, Luke; Fogarty, Laurel; Laland, Kevin N

    2011-03-27

    Cultural niche construction is a uniquely potent source of selection on human populations, and a major cause of recent human evolution. Previous theoretical analyses have not, however, explored the local effects of cultural niche construction. Here, we use spatially explicit coevolutionary models to investigate how cultural processes could drive selection on human genes by modifying local resources. We show that cultural learning, expressed in local niche construction, can trigger a process with dynamics that resemble runaway sexual selection. Under a broad range of conditions, cultural niche-constructing practices generate selection for gene-based traits and hitchhike to fixation through the build up of statistical associations between practice and trait. This process can occur even when the cultural practice is costly, or is subject to counteracting transmission biases, or the genetic trait is selected against. Under some conditions a secondary hitchhiking occurs, through which genetic variants that enhance the capability for cultural learning are also favoured by similar dynamics. We suggest that runaway cultural niche construction could have played an important role in human evolution, helping to explain why humans are simultaneously the species with the largest relative brain size, the most potent capacity for niche construction and the greatest reliance on culture.

  20. The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb

    PubMed Central

    Gengatharan, Archana; Bammann, Rodrigo R.; Saghatelyan, Armen

    2016-01-01

    In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

  1. Engineering the niche for stem cells.

    PubMed

    Tan, Shawna; Barker, Nicholas

    2013-12-01

    Much has been made about the potential for stem cells in regenerative medicine but the reality is that the development of actual therapies has been slow. Adult stem cells rely heavily on the assortment of biochemical and biophysical elements that constitute the local microenvironment in which they exist. One goal of biomedicine is to create an artificial yet biofunctional niche to support multipotency, differentiation and proliferation. Such tools would facilitate more conclusive experimentation by biologists, pharmaceutical scientists and tissue engineers. While many bioengineering techniques and platforms are already in use, technological innovations now allow this to be done at a higher resolution and specificity. Ultimately, the multidisciplinary integration of engineering and biology will allow the niche to be generated at a scale that can be clinically exploited. Using the systems that constitute the intestinal, hematopoietic and epidermal tissues, this article summarizes the various approaches and tools currently employed to recreate stem cell niches and also explores recent advances in the field. PMID:24274105

  2. Engineering the niche for stem cells.

    PubMed

    Tan, Shawna; Barker, Nicholas

    2013-12-01

    Much has been made about the potential for stem cells in regenerative medicine but the reality is that the development of actual therapies has been slow. Adult stem cells rely heavily on the assortment of biochemical and biophysical elements that constitute the local microenvironment in which they exist. One goal of biomedicine is to create an artificial yet biofunctional niche to support multipotency, differentiation and proliferation. Such tools would facilitate more conclusive experimentation by biologists, pharmaceutical scientists and tissue engineers. While many bioengineering techniques and platforms are already in use, technological innovations now allow this to be done at a higher resolution and specificity. Ultimately, the multidisciplinary integration of engineering and biology will allow the niche to be generated at a scale that can be clinically exploited. Using the systems that constitute the intestinal, hematopoietic and epidermal tissues, this article summarizes the various approaches and tools currently employed to recreate stem cell niches and also explores recent advances in the field.

  3. Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells

    PubMed Central

    Razavi, Shahnaz; Jahromi, Maliheh; Amirpour, Nushin; Khosravizadeh, Zahra

    2014-01-01

    Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 μM Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs. PMID:24800186

  4. Niche construction in the light of niche theory.

    PubMed

    Kylafis, Grigoris; Loreau, Michel

    2011-02-01

    Ecological niche construction, the process whereby an organism improves its environment to enhance its growth and persistence, is an important missing element of niche theory. Niche theory has mainly focused on niche-deteriorating processes, such as resource consumption, predation and competition, which have negative effects on population growth. Here, we integrate niche construction explicitly into modern niche theory. We use a graphical approach to analyse how a species' niche-improving impacts interplay with niche-deteriorating impacts to modify its response to the environment. In a model of two consumers that compete for one limiting resource and one predator, we show how niche construction modifies the traditional niche-deteriorating impacts of its agent or of competing species, and hence the potential for species coexistence. By altering the balance between intraspecific and interspecific competitive effects, niche construction can either generate net interspecific facilitation or strengthen interspecific competition. The adaptive benefit derived from niche construction also strongly affects the realized niche of a niche-constructing species.

  5. Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension

    PubMed Central

    Hauser, Robert A.; Heritier, Stephane; Rowse, Gerald J.; Hewitt, L. Arthur; Isaacson, Stuart H.

    2016-01-01

    Objectives Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Methods Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. Results A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Conclusions Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed. PMID:27332626

  6. A neurogenic basis for acute altitude illness.

    PubMed

    Krasney, J A

    1994-02-01

    Acute altitude illnesses include acute mountain sickness (AMS), a benign condition involving headache, nausea, vomiting, irritability, insomnia, dizziness, lethargy, and peripheral edema, and potentially lethal high-altitude cerebral edema and pulmonary edema (HAPE). Recent evidence is summarized that AMS is related to cerebral edema secondary at least in part to hypoxic cerebral vasodilation and elevated cerebral capillary hydrostatic pressure. This results in reduced brain compliance with compression of intracranial structures in the absence of altered global brain metabolism. It is postulated that these primary intracranial events elevate peripheral sympathetic activity that acts neurogenically in the lung possibly in concert with pulmonary capillary stress failure to cause HAPE and in the kidney to promote salt and water retention. The adrenergic responses are likely modulated by striking increases of aldosterone, vasopressin and atrial natriuretic peptide. The effects of exercise on altitude-induced illness and various therapeutic regimens (acetazolamide, CO2 breathing, dexamethasone, and alpha adrenergic inhibitors) are discussed in light of this hypothesis.

  7. Astrocyte fatty acid binding protein-7 is a marker for neurogenic niches in the rat hippocampus.

    PubMed

    Young, John K; Heinbockel, Thomas; Gondré-Lewis, Marjorie C

    2013-12-01

    Recent research has determined that newborn neurons in the dentate gyrus of the hippocampus of the macaque are frequently adjacent to astrocytes immunoreactive for fatty acid binding protein-7 (FABP7). To investigate if a similar relationship between FABP7-positive (FABP7+) astrocytes and proliferating cells exists in the rodent brain, sections of brains from juvenile rats were stained by immunohistochemistry to demonstrate newborn cells (antibody to Ki67 protein) and FABP7+ astrocytes. In rat brains, FABP7+ astrocytes were particularly abundant in the dentate gyrus of the hippocampus and were frequently close to dividing cells immunoreactive for Ki67 protein. FABP7+ astrocytes were also present in the olfactory bulbs, arcuate nucleus of the hypothalamus, and in the dorsal medulla subjacent to the area postrema, sites where more modest numbers of newborn neurons can also be found. These data suggest that regional accumulations of FABP7+ astrocytes may represent reservoirs of cells having the potential for neurogenesis. Because FABP7+ astrocytes are particularly abundant in the hippocampus, and since the gene for FABP7 has been linked to Alzheimer's disease, age-related changes in FABP7+ astrocytes (mitochondrial degeneration) may be relevant to age-associated disorders of the hippocampus.

  8. Urinary tract infection in the neurogenic bladder

    PubMed Central

    Vigil, Humberto R.

    2016-01-01

    There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥103 CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5–14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required. PMID:26904414

  9. Photosensitive neurogenic heart of the isopod crustacean Ligia exotica

    PubMed Central

    Miyamoto, Hiroshi; Horiguchi, Hiroko; Hariyama, Takahiko; Takano, Satoshi; Yamagishi, Hiroshi

    2006-01-01

    The heart of animals is regulated through the central nervous system in response to external sensory stimuli. We found, however, that the adult neurogenic heart of the isopod crustacean Ligia exotica has photosensitivity. The beat frequency of the isolated heart decreased in response to a light stimulus. Magnitude of the response was stimulus intensity dependent and the heartbeat frequency decreased to less than 80% of the dark value during illumination of the white light with an intensity of 6.0 mW cm−2. The spectral sensitivity curve of the heart photoresponse peaked at a wavelength around 520 nm. In response to 530 nm monochromatic light, the relationship between light intensity and response magnitude was linear and the threshold intensity was 7.26×1012 quanta cm−2 s−1. Bursting activity of the cardiac ganglion, which is located in the heart and acts as the cardiac pacemaker deceased in frequency in response to illumination by white light. This fact suggests that the heart photoresponse of L. exotica results from the photosensitivity of the cardiac ganglion neurons. The photoresponse of the heart therefore contributes to regulation of cardiac output in addition to other regulatory systems. PMID:16959646

  10. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  11. Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis

    PubMed Central

    Ferrón, S. R.; Radford, E. J.; Domingo-Muelas, A.; Kleine, I.; Ramme, A.; Gray, D.; Sandovici, I.; Constancia, M.; Ward, A.; Menheniott, T. R.; Ferguson-Smith, A. C.

    2015-01-01

    Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis. PMID:26369386

  12. Conversion of quiescent niche cells to somatic stem cells causes ectopic niche formation in the Drosophila testis

    PubMed Central

    Hétié, Phylis; de Cuevas, Margaret; Matunis, Erika

    2014-01-01

    Summary Adult stem cells reside in specialized regulatory microenvironments, or niches, where local signals ensure stem cell maintenance. The Drosophila testis contains a well-characterized niche wherein signals from post-mitotic hub cells promote maintenance of adjacent germline stem cells and somatic cyst stem cells (CySCs). Hub cells were considered to be terminally differentiated; here we show that they can give rise to CySCs. Genetic ablation of CySCs triggers hub cells to transiently exit quiescence, delaminate from the hub, and convert into functional CySCs. Ectopic Cyclin D-Cdk4 expression in hub cells is also sufficient to trigger their conversion into CySCs. In both cases, this conversion causes the formation of multiple ectopic niches over time. Therefore, our work provides a model for understanding how oncogenic mutations in quiescent niche cells could promote loss of quiescence, changes in cell fate, and aberrant niche expansion more generally. PMID:24746819

  13. Coronavirus-induced demyelination of neural pathways triggers neurogenic bladder overactivity in a mouse model of multiple sclerosis

    PubMed Central

    McMillan, Matthew T.; Pan, Xiao-Qing; Smith, Ariana L.; Newman, Diane K.; Weiss, Susan R.; Ruggieri, Michael R.

    2014-01-01

    In the present study, we aimed to determine whether mice with coronavirus-induced encephalomyelitis (CIE) develop neurogenic bladder dysfunction that is comparable with the neurogenic detrusor overactivity observed in patients with multiple sclerosis. Adult mice (C57BL/6J, 8 wk of age, n = 146) were inoculated with a neurotropic strain of mouse hepatitis virus (A59 strain) and followed for 4 wk. Inoculation with the virus caused a significant neural deficit in mice with an average clinical symptom score of 2.6 ± 0.5 at 2 wk. These changes were accompanied by 25 ± 5% weight loss at 1 and 2 wk postinoculation (P ≤ 0.001 vs. baseline) followed by a recovery phase. Histological analysis of spinal cord sections revealed multifocal sites of demyelinated lesions. Assessment of micturition patterns by filter paper assay determined an increase in the number of small and large urine spots in CIE mice starting from the second week after inoculation. Cystometric recordings in unrestrained awake animals confirmed neurogenic bladder overactivity at 4 wk postinoculation. One week after inoculation with the A59 strain of mouse hepatitis virus, mice became increasingly sensitive to von Frey filament testing with responses enhanced by 45% (n = 8, P ≤ 0.05 vs. baseline at 4 g); however, this initial increase in sensitivity was followed by gradual and significant diminution of abdominal sensitivity to mechanical stimulation by 4 wk postinoculation. Our results provide direct evidence showing that coronavirus-induced demyelination of the central nervous system causes the development of a neurogenic bladder that is comparable with neurogenic detrusor overactivity observed in patients with multiple sclerosis. PMID:25007876

  14. Microglia participate in neurogenic regulation of hypertension.

    PubMed

    Shen, Xiao Z; Li, You; Li, Liang; Shah, Kandarp H; Bernstein, Kenneth E; Lyden, Patrick; Shi, Peng

    2015-08-01

    Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure.

  15. Does Race/Ethnicity Really Matter in Adult Neurogenics?

    ERIC Educational Resources Information Center

    Ellis, Charles

    2009-01-01

    Purpose: Recent evidence suggests that race/ethnicity is a variable that is critical to outcomes in neurological disorders. The purpose of this article was to examine the proportion of studies published in the "American Journal of Speech-Language Pathology (AJSLP)" and the "Journal of Speech, Language, and Hearing Research (JSLHR)" that were…

  16. The Multidimensional Nutritional Niche.

    PubMed

    Machovsky-Capuska, Gabriel E; Senior, Alistair M; Simpson, Stephen J; Raubenheimer, David

    2016-05-01

    The dietary generalist-specialist distinction plays a pivotal role in theoretical and applied ecology, conservation, invasion biology, and evolution and yet the concept remains poorly characterised. Diets, which are commonly used to define niche breadth, are almost exclusively considered in terms of foods, with little regard for the mixtures of nutrients and other compounds they contain. We use nutritional geometry (NG) to integrate nutrition with food-level approaches to the dietary niche and illustrate the application of our framework in the important context of invasion biology. We use an example that involves a model with four hypothetical nonexclusive scenarios. We additionally show how this approach can provide fresh theoretical insight into the ways nutrition and food choices impact trait evolution and trophic interactions.

  17. Life history, cognition and the evolution of complex foraging niches.

    PubMed

    Schuppli, Caroline; Graber, Sereina M; Isler, Karin; van Schaik, Carel P

    2016-03-01

    Animal species that live in complex foraging niches have, in general, improved access to energy-rich and seasonally stable food sources. Because human food procurement is uniquely complex, we ask here which conditions may have allowed species to evolve into such complex foraging niches, and also how niche complexity is related to relative brain size. To do so, we divided niche complexity into a knowledge-learning and a motor-learning dimension. Using a sample of 78 primate and 65 carnivoran species, we found that two life-history features are consistently correlated with complex niches: slow, conservative development or provisioning of offspring over extended periods of time. Both act to buffer low energy yields during periods of learning, and may thus act as limiting factors for the evolution of complex niches. Our results further showed that the knowledge and motor dimensions of niche complexity were correlated with pace of development in primates only, and with the length of provisioning in only carnivorans. Accordingly, in primates, but not carnivorans, living in a complex foraging niche requires enhanced cognitive abilities, i.e., a large brain. The patterns in these two groups of mammals show that selection favors evolution into complex niches (in either the knowledge or motor dimension) in species that either develop more slowly or provision their young for an extended period of time. These findings help to explain how humans constructed by far the most complex niche: our ancestors managed to combine slow development (as in other primates) with systematic provisioning of immatures and even adults (as in carnivorans). This study also provides strong support for the importance of ecological factors in brain size evolution. PMID:26989019

  18. A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

    PubMed Central

    Ribeiro Xavier, Anna L.; Kress, Benjamin T.; Goldman, Steven A.; Lacerda de Menezes, João R.

    2015-01-01

    Microglia are involved in synaptic pruning both in development and in the mature CNS. In this study, we investigated whether microglia might further contribute to circuit plasticity by modulating neuronal recruitment from the neurogenic subventricular zone (SVZ) of the adult mouse striatum. We found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low expression of purinoceptors and lack of ATP-elicitable chemotaxis. Furthermore, the in vivo depletion of these microglia hampered the survival and migration of newly generated neuroblasts through the RMS to the olfactory bulb. SVZ and RMS microglia thus appear to comprise a functionally distinct class that is selectively adapted to the support and direction of neuronal integration into the olfactory circuitry. Therefore, this unique microglial subpopulation may serve as a novel target with which to modulate cellular addition from endogenous neural stem and progenitor cells of the adult brain. SIGNIFICANCE STATEMENT Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural circuitry sculpture. Here, we addressed microglial functions in the subventricular zone (SVZ), the major postnatal neurogenic niche. Our results depict microglia as a conspicuous component of SVZ and its anterior extension, the rostral migratory stream, a pathway used by neuroblasts during their transit toward olfactory bulb layers. In addition to other unique populations residing in the SVZ niche, microglia display distinct morphofunctional properties that boost neuronal

  19. Electrical management of neurogenic lower urinary tract disorders.

    PubMed

    Joussain, C; Denys, P

    2015-09-01

    Management of lower urinary tract dysfunction (LUTD) in neurological diseases remains a priority because it leads to many complications such as incontinence, renal failure and decreased quality of life. A pharmacological approach remains the first-line treatment for patients with neurogenic LUTD, but electrical stimulation is a well-validated and recommended second-line treatment. However, clinicians must be aware of the indications, advantages and side effects of the therapy. This report provides an update on the 2 main electrical stimulation therapies for neurogenic LUTD - inducing direct bladder contraction with the Brindley procedure and modulating LUT physiology (sacral neuromodulation, tibial posterior nerve stimulation or pudendal nerve stimulation). We also describe the indications of these therapies for neurogenic LUTD, following international guidelines, as illustrated by their efficacy in patients with neurologic disorders. Electrical stimulation could be proposed for neurogenic LUTD as second-line treatment after failure of oral pharmacologic approaches. Nevertheless, further investigations are needed for a better understanding of the mechanisms of action of these techniques and to confirm their efficacy. Other electrical investigations, such as deep-brain stimulation and repetitive transcranial magnetic stimulation, or improved sacral anterior root stimulation, which could be associated with non-invasive and highly specific deafferentation of posterior roots, may open new fields in the management of neurogenic LUTD. PMID:26321622

  20. S100A6 (calcyclin) is a novel marker of neural stem cells and astrocyte precursors in the subgranular zone of the adult mouse hippocampus.

    PubMed

    Yamada, Jun; Jinno, Shozo

    2014-01-01

    S100A6 (calcyclin), an EF-hand calcium binding protein, is considered to play various roles in the brain, for example, cell proliferation and differentiation, calcium homeostasis, and neuronal degeneration. In addition to some limbic nuclei, S100A6 is distributed in the rostral migratory stream, one of the major neurogenic niches of the adult brain. However, the potential involvement of S100A6 in adult neurogenesis remains unclear. In this study, we aimed to elucidate the role of S100A6 in the other major neurogenic niche, the subgranular zone of the dentate gyrus in the adult mouse hippocampus. Immunofluorescent multiple labeling showed that S100A6 was highly expressed in neural stem cells labeled by sex determining region Y-box 2, brain lipid-binding protein protein and glial fibrillary acidic protein. S100A6+ cells often extended a long process typical of radial glial morphology. In addition, S100A6 was found in some S100β+ astrocyte lineage cells. Interestingly, proliferating cell nuclear antigen was detected in a fraction of S100A6+/S100β+ cells. These cells were considered to be lineage-restricted astrocyte precursors maintaining mitotic potential. On the other hand, S100A6 was rarely seen in neural lineage cells labeled by T-box brain protein 2, doublecortin, calretinin and calbindin D28K. Cell fate-tracing experiment using BrdU showed that the majority of newly generated immature astrocytes were immunoreactive for S100A6, while mature astrocytes lacked S100A6 immunoreactivity. Administration of S100 protein inhibitor, trifluoperazine, caused a reduction in production of S100β+ astrocyte lineage cells, but had no impact on neurogenesis. Overall, our data provide the first evidence that S100A6 is a specific marker of neural stem cells and astrocyte precursors, and may be especially important for generation of astrocytes in the adult hippocampus.

  1. Making Blood: The Haematopoietic Niche throughout Ontogeny

    PubMed Central

    Al-Drees, Mohammad A.; Yeo, Jia Hao; Boumelhem, Badwi B.; Antas, Veronica I.; Brigden, Kurt W. L.; Colonne, Chanukya K.; Fraser, Stuart T.

    2015-01-01

    Approximately one-quarter of all cells in the adult human body are blood cells. The haematopoietic system is therefore massive in scale and requires exquisite regulation to be maintained under homeostatic conditions. It must also be able to respond when needed, such as during infection or following blood loss, to produce more blood cells. Supporting cells serve to maintain haematopoietic stem and progenitor cells during homeostatic and pathological conditions. This coalition of supportive cell types, organised in specific tissues, is termed the haematopoietic niche. Haematopoietic stem and progenitor cells are generated in a number of distinct locations during mammalian embryogenesis. These stem and progenitor cells migrate to a variety of anatomical locations through the conceptus until finally homing to the bone marrow shortly before birth. Under stress, extramedullary haematopoiesis can take place in regions that are typically lacking in blood-producing activity. Our aim in this review is to examine blood production throughout the embryo and adult, under normal and pathological conditions, to identify commonalities and distinctions between each niche. A clearer understanding of the mechanism underlying each haematopoietic niche can be applied to improving ex vivo cultures of haematopoietic stem cells and potentially lead to new directions for transplantation medicine. PMID:26113865

  2. Purinergic signaling promotes proliferation of adult mouse subventricular zone cells.

    PubMed

    Suyama, Satoshi; Sunabori, Takehiko; Kanki, Hiroaki; Sawamoto, Kazunobu; Gachet, Christian; Koizumi, Schuichi; Okano, Hideyuki

    2012-07-01

    In adult mammalian brains, neural stem cells (NSCs) exist in the subventricular zone (SVZ), where persistent neurogenesis continues throughout life. Those NSCs produce neuroblasts that migrate into the olfactory bulb via formation of transit-amplifying cells, which are committed precursor cells of the neuronal lineage. In this SVZ niche, cell-cell communications conducted by diffusible factors as well as physical cell-cell contacts are important for the regulation of the proliferation and fate determination of NSCs. Previous studies have suggested that extracellular purinergic signaling, which is mediated by purine compounds such as ATP, plays important roles in cell-cell communication in the CNS. Purinergic signaling also promotes the proliferation of adult NSCs in vitro. However, the in vivo roles of purinergic signaling in the neurogenic niche still remain unknown. In this study, ATP infusion into the lateral ventricle of the mouse brain resulted in an increase in the numbers of rapidly dividing cells and Mash1-positive transit-amplifying cells (Type C cells) in the SVZ. Mash1-positive cells express the P2Y1 purinergic signaling receptor and infusion of the P2Y1 receptor-specific antagonist MRS2179 decreased the number of rapidly dividing bromodeoxyuridine (BrdU)-positive cells and Type C cells. Moreover, a 17% reduction of rapidly dividing BrdU-positive cells and a 19% reduction of Mash1-positive cells were observed in P2Y1 knock-out mice. Together, these results suggest that purinergic signaling promotes the proliferation of rapidly dividing cells and transit-amplifying cells, in the SVZ niche through the P2Y1 receptor. PMID:22764232

  3. Mini-gut organoids: reconstitution of the stem cell niche.

    PubMed

    Date, Shoichi; Sato, Toshiro

    2015-01-01

    In the adult mammalian body, self-renewal of tissue stem cells is regulated by extracellular niche environments in response to the demands of tissue organization. Intestinal stem cells expressing Lgr5 constantly self-renew in their specific niche at the crypt bottom to maintain rapid turnover of the epithelium. Niche-regulated stem cell self-renewal is perturbed in several mouse genetic models and during human tumorigenesis, suggesting roles for EGF, Wnt, BMP/TGF-β, and Notch signaling. In vitro niche reconstitution capitalizing on this knowledge has enabled the growth of single intestinal stem cells into mini-gut epithelial organoids comprising Lgr5(+) stem cells and all types of differentiated lineages. The mini-gut organoid culture platform is applicable to various types of digestive tissue epithelium from multiple species. The mechanism of self-renewal in organoids provides novel insights for organogenesis, regenerative medicine, and tumorigenesis of the digestive system. PMID:26436704

  4. Aging of the subventricular zone neural stem cell niche.

    PubMed

    Conover, Joanne C; Shook, Brett A

    2011-02-01

    The persistence of an active subventricular zone neural stem cell niche in the adult mammalian forebrain supports its continued role in the production of new neurons and in generating cells to function in repair through adulthood. Unfortunately, with increasing age the niche begins to deteriorate, compromising these functions. The reasons for this decline are not clear. Studies are beginning to define the molecular and physiologic changes in the microenvironment of the aging subventricular zone niche. New revelations from aging studies will allow for a more thorough understanding of which reparative functions are lost in the aged brain, the progression of niche demise and the possibility for therauptic intervention to improve aging brain function. PMID:22396866

  5. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    PubMed

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner. PMID:25256750

  6. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    PubMed

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner.

  7. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells.

    PubMed

    Mahajan, Pradeep V; Subramanian, Swetha; Danke, Amit; Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID:27656308

  8. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells

    PubMed Central

    Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted.

  9. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells

    PubMed Central

    Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID:27656308

  10. Finding a Niche

    PubMed Central

    2010-01-01

    Although I always knew I wanted to be a scientist, I didn't know I would become a cell biologist. Events in life that you would never have predicted can greatly impact your career trajectory. I have learned to let those events take me in new directions. Following a desire to investigate an understudied area of cell biology, I have found a niche. In this area, my lab is poised to contribute significantly toward understanding the fundamental molecular mechanisms underlying polarized plant cell growth. PMID:21079002

  11. In defense of 'niche modeling'.

    PubMed

    Warren, Dan L

    2012-09-01

    There is a growing awareness of problems with the estimation of the ecological tolerances of species through correlative modeling approaches. These problems have led some investigators to argue for abandoning terms such as 'ecological niche model' and 'environmental niche model' in favor of the ostensibly more value-neutral 'species distribution model', as the models are thought to frequently be poor estimators of the niche. Here, I argue that most applications to which these models are put require the assumption that they do estimate the niche, however imperfectly, and that obscuring this inescapable and potentially flawed assumption in the terminology may only serve to hinder the development of the field.

  12. Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate.

    PubMed

    Lecca, Davide; Fumagalli, Marta; Ceruti, Stefania; Abbracchio, Maria P

    2016-08-01

    In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific 'neurogenic' areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self-repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377726

  13. Heat freezes niche evolution.

    PubMed

    Araújo, Miguel B; Ferri-Yáñez, Francisco; Bozinovic, Francisco; Marquet, Pablo A; Valladares, Fernando; Chown, Steven L

    2013-09-01

    Climate change is altering phenology and distributions of many species and further changes are projected. Can species physiologically adapt to climate warming? We analyse thermal tolerances of a large number of terrestrial ectotherm (n = 697), endotherm (n = 227) and plant (n = 1816) species worldwide, and show that tolerance to heat is largely conserved across lineages, while tolerance to cold varies between and within species. This pattern, previously documented for ectotherms, is apparent for this group and for endotherms and plants, challenging the longstanding view that physiological tolerances of species change continuously across climatic gradients. An alternative view is proposed in which the thermal component of climatic niches would overlap across species more than expected. We argue that hard physiological boundaries exist that constrain evolution of tolerances of terrestrial organisms to high temperatures. In contrast, evolution of tolerances to cold should be more frequent. One consequence of conservatism of upper thermal tolerances is that estimated niches for cold-adapted species will tend to underestimate their upper thermal limits, thereby potentially inflating assessments of risk from climate change. In contrast, species whose climatic preferences are close to their upper thermal limits will unlikely evolve physiological tolerances to increased heat, thereby being predictably more affected by warming.

  14. Boundary Caps Give Rise to Neurogenic Stem Cells and Terminal Glia in the Skin

    PubMed Central

    Gresset, Aurélie; Coulpier, Fanny; Gerschenfeld, Gaspard; Jourdon, Alexandre; Matesic, Graziella; Richard, Laurence; Vallat, Jean-Michel; Charnay, Patrick; Topilko, Piotr

    2015-01-01

    Summary While neurogenic stem cells have been identified in rodent and human skin, their manipulation and further characterization are hampered by a lack of specific markers. Here, we perform genetic tracing of the progeny of boundary cap (BC) cells, a neural-crest-derived cell population localized at peripheral nerve entry/exit points. We show that BC derivatives migrate along peripheral nerves to reach the skin, where they give rise to terminal glia associated with dermal nerve endings. Dermal BC derivatives also include cells that self-renew in sphere culture and have broad in vitro differentiation potential. Upon transplantation into adult mouse dorsal root ganglia, skin BC derivatives efficiently differentiate into various types of mature sensory neurons. Together, this work establishes the embryonic origin, pathway of migration, and in vivo neurogenic potential of a major component of skin stem-like cells. It provides genetic tools to study and manipulate this population of high interest for medical applications. PMID:26212662

  15. Staphylococcal Enterotoxin B Causes Proliferation of Sensory C-Fibers and Subsequent Enhancement of Neurogenic Inflammation in Rat Skin

    PubMed Central

    Ohshima, Mihoko; Miyake, Mio; Takeda, Masanori; Kamijima, Michihiro

    2011-01-01

    Background. Staphylococcal enterotoxin B (SEB) may be associated with the exacerbation of atopic dermatitis. We investigated whether SEB causes proliferation of sensory C-fibers and subsequent enhancement of plasma leakage induced by sensorineural stimulation in rat skin. Methods. SEB was applied intracutaneously to the abdomen of preweaning and adult rats. Evans blue dye leakage into the skin induced by topical 10% formalin was measured as an index of neurogenic skin vascular permeability. Local expression of substance P, tachykinin NK1 receptors, and nerve growth factor was assessed immunohistochemically. In addition, we assessed the effects of topical tacrolimus on these skin responses induced by SEB. Results. Increased neurogenic skin plasma leakage was seen 7 days after SEB treatment in 2 different age groups. Innervation of substance P-immunoreactive nerves and expression of tachykinin NK1 receptors and nerve growth factor were also promoted by SEB, peaking at 7 days, 7 days, and 56 h after SEB treatment, respectively. Tacrolimus markedly inhibited these skin changes. Conclusions. SEB increased the innervation of sensory C-fibers and tachykinin NK1 receptors in rat skin, probably because of upregulated production of neurotrophins, including nerve growth factor, leading to enhancement of neurogenic skin inflammation. T cell activation induced by SEB may initiate these changes. PMID:21252260

  16. SUSCEPTIBILITY TO POLLUTANT-INDUCED AIRWAY INFLAMMATION IS NEUROGENICALLY MEDIATED.

    EPA Science Inventory

    Neurogenic inflammation in the airways involves the activation of sensory irritant receptors (capsaicin, VR1) by noxious stimuli and the subsequent release of neuropeptides (e.g., SP, CGRP, NKA) from these fibers. Once released, these peptides initiate and sustain symptoms of ...

  17. Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes

    PubMed Central

    Boku, Shuken; Hisaoka-Nakashima, Kazue; Nakagawa, Shin; Kato, Akiko; Kajitani, Naoto; Inoue, Takeshi; Kusumi, Ichiro; Takebayashi, Minoru

    2013-01-01

    Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG), which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP), we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI), a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA). These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM) from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes. PMID:24260208

  18. Not all neurogenic bladders are the same: a proposal for a new neurogenic bladder classification system

    PubMed Central

    2016-01-01

    Neurogenic bladder (NGB) has long been defined as a clinical entity that describes a heterogeneous collection of syndromes. The common theme is a bladder disorder concomitant with a neurologic disorder. This definition does not give the clinician much information about the bladder disorder, nor how to treat it, or even what the natural history of the disorder is likely to be. It may be time for a new classification scheme to better define the bladder defect and prognosis, as well as inform treatment. We propose a classification system based on seven categories, each having a neurologic defect in a distinct anatomic location. This is termed SALE (Stratify by Anatomic Location and Etiology). In addition, the presence or absence of bowel dysfunction and autonomic dysreflexia will be reported. In the future, as more definite prognostic information can be gleaned from biomarkers, we anticipate adding urinary nerve growth factor (NGF) and urinary brain-derived neurotrophic factor (BDNF) levels to the definition. We expect the SALE system to efficiently describe a patient suffering from NGB and simultaneously inform the most appropriate treatment, follow-up regimen, and long-term prognosis. PMID:26904408

  19. Communication between bone marrow niches in normal bone marrow function and during hemopathies progression

    PubMed Central

    Lamorte, Sara; Remédio, Leonor; Dias, Sergio

    2009-01-01

    Hematopoietic stem cell (HSC) chemotaxis, adhesion, proliferation, quiescence and differentiation are regulated by interactions with bone marrow (BM) niches. Two niches have been identified in the adult BM: the endosteal (close to the bone) and the perivascular niche (close to blood vessels). A vast body of literature has revealed the molecular basis for the interaction of HSCs with the two niches. However, the signals that regulate the communication between the two niches have not been well defined. Taking in consideration several clinical and experimental arguments this review highlights the molecular cues, involved in the communication between the BM niches, which regulate the basic properties of HSCs in physiological and malignant conditions. As such, it aims at clarifying the most important advances in basic and clinical research focusing on the role of different factors in the regulation of the BM microenvironment.

  20. Beyond the Niche: Tissue-Level Coordination of Stem Cell Dynamics

    PubMed Central

    O’Brien, Lucy Erin; Bilder, David

    2014-01-01

    Adult animals rely on populations of stem cells to ensure organ function throughout their lifetime. Stem cells are governed by signals from stem cell niches, and much is known about how single niches promote stemness and direct stem cell behavior. However, most organs contain a multitude of stem cell–niche units, which are often distributed across the entire expanse of the tissue. Beyond the biology of individual stem cell–niche interactions, the next challenge is to uncover the tissue-level processes that orchestrate spatial control of stem-based renewal, repair, and remodeling throughout a whole organ. Here we examine what is known about higher order mechanisms for interniche coordination in epithelial organs, whose simple geometry offers a promising entry point for understanding the regulation of niche number, distribution, and activity. We also consider the potential existence of stem cell territories and how tissue architecture may influence niche coordination. PMID:23937350

  1. Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers.

    PubMed

    Lengil, Tamar; Gancz, Dana; Gilboa, Lilach

    2015-03-01

    How the numbers of niches and resident stem cells within a particular organ are determined during development and how they may be modulated or corrected is a question with significant medical implications. In the larval ovary of Drosophila melanogaster, somatic precursors for niches, and germ cells that will become germline stem cells, co-develop. Somatic precursors proliferate during the first 3 days of larval development. By mid-third instar, adult terminal filament (TF) (part of the germline stem cell niche) cells first appear, and differentiation terminates 24 h later when 16-20 TFs fully form. The developmental sequence responsible for TF cell determination and final TF numbers is only partially understood. We show that TF formation proceeds through several, hitherto uncharacterized stages, which include an early exit from the cell cycle to form TF precursors and two steps of cell shape change to form the mature TF cells. The Activin receptor Baboon (Babo) is required for somatic precursor cell proliferation and therefore determines the pool of TF precursors available for TF differentiation. During the final differentiation stage, Babo facilitates TF and germ cell differentiation, and promotes the accumulation of Broad-Z1, which is also a target of the steroid hormone ecdysone. Epistasis analysis shows that Activin controls cell proliferation in an ecdysone-independent manner and TF differentiation by affecting ecdysone targets. We propose that this mode of function allows Activin to balance proliferation and differentiation, and to equilibrate niche numbers. These results suggest a novel model for how niche numbers are corrected during development.

  2. Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators.

    PubMed

    Desai, Mina; Han, Guang; Ross, Michael G

    2016-04-01

    Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. PMID:26785315

  3. Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators.

    PubMed

    Desai, Mina; Han, Guang; Ross, Michael G

    2016-04-01

    Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring.

  4. The stem cell niche finds its true north.

    PubMed

    Kirkeby, Agnete; Perlmann, Thomas; Pereira, Carlos-Filipe

    2016-08-15

    The third 'Stem Cell Niche' meeting, supported by The Novo Nordisk Foundation, was held this year on May 22-26 and brought together 185 selected participants from 24 different countries to Hillerød, Denmark. Diverse aspects of embryonic and adult stem cell biology were discussed, including their respective niches in ageing, disease and regeneration. Many presentations focused on emerging technologies, including single-cell analysis, in vitro organogenesis and direct reprogramming. Here, we summarize the data presented at this exciting and highly enjoyable meeting, where speakers as well as kitchen chefs were applauded at every session. PMID:27531947

  5. [Neurogenic communication disorders: how effective are relaxation therapy and acupuncture?].

    PubMed

    Ptok, M

    2008-12-01

    Not only neurologists but also ENT-physicians and phoniatricians have to prescribe speech and language therapy for patients with communication disorders. Complementary and alternative medicine (CAM) has gained increasing popularity among patients. Many studies have investigated these procedures and positive effects on certain physical e. g., chronic pain and anxiety disorders could be validated. Unfortunately only few empirical investigations have targeted the use of CAM to treat neurogenic disorders of communication or cognition. In this review we provide an overview over general therapeutical principals of two widely used approaches, relaxation therapy and acupuncture. Then we survey the literature and summarize existent research literature regarding the effects of the treatment of neurogenic disorders including dementia.

  6. The treatment of erectile dysfunction in patients with neurogenic disease

    PubMed Central

    Brant, William O.

    2016-01-01

    Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED. PMID:26904415

  7. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome.

    PubMed

    Littlejohn, Geoffrey

    2015-11-01

    Although fibromyalgia and complex regional pain syndrome (CRPS) have distinct clinical phenotypes, they do share many other features. Pain, allodynia and dysaesthesia occur in each condition and seem to exist on a similar spectrum. Fibromyalgia and CRPS can both be triggered by specific traumatic events, although fibromyalgia is most commonly associated with psychological trauma and CRPS is most often associated with physical trauma, which is frequently deemed routine or minor by the patient. Fibromyalgia and CRPS also seem to share many pathophysiological mechanisms, among which the most important are those involving central effects. Nonetheless, peripheral effects, such as neurogenic neuroinflammation, are also important contributors to the clinical features of each of these disorders. This Review highlights the differing degrees to which neurogenic neuroinflammation might contribute to the multifactorial pathogenesis of both fibromyalgia and CRPS, and discusses the evidence suggesting that this mechanism is an important link between the two disorders, and could offer novel therapeutic targets.

  8. Peripheral tumor and tumor-like neurogenic lesions.

    PubMed

    Abreu, Evandro; Aubert, Sébastien; Wavreille, Guillaume; Gheno, Ramon; Canella, Clarissa; Cotten, Anne

    2013-01-01

    Neoplasms of neurogenic origin account for about 12% of all benign and 8% of all malignant soft tissue neoplasms. Traumatic neuroma, Morton neuroma, lipomatosis of a nerve, nerve sheath ganglion, perineurioma, benign and malignant peripheral nerve sheath tumors (PNST) are included in this group of pathologies. Clinical and radiologic evaluation of patients with neurogenic tumors and pseudotumors often reveals distinctive features. In this context, advanced imaging techniques, especially ultrasound (US) and magnetic resonance (MR) play an important role in the characterization of these lesions. Imaging findings such as location of a soft tissue mass in the region of a major nerve, nerve entering or exiting the mass, fusiform shape, abnormalities of the muscle supplied by the nerve, split-fat sign, target sign and fascicular appearance should always evoke a peripheric nerve sheath neoplasm. Although no single imaging finding or combination of findings allows definitive differentiation between benign from malign peripheric neurogenic tumors, both US and MR imaging may show useful features that can lead us to a correct diagnosis and improve patient treatment. Traumatic neuromas and Morton neuromas are commonly associated to an amputation stump or are located in the intermetatarsal space. Lipomatosis of a nerve usually appears as a nerve enlargement, with thickened nerve fascicles, embedded in evenly distributed fat. Nerve sheath ganglion has a cystic appearance and commonly occurs at the level of the knee. Intraneural perineuroma usually affects young people and manifests as a focal and fusiform nerve enlargement. In this article, we review clinical characteristics and radiologic appearances of these neurogenic lesions, observing pathologic correlation, when possible.

  9. Medical management of neurogenic bladder with oral therapy

    PubMed Central

    2016-01-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series. PMID:26904412

  10. Medical management of neurogenic bladder with oral therapy.

    PubMed

    Cameron, Anne P

    2016-02-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series.

  11. Preemptive analgesia: the prevention of neurogenous orofacial pain.

    PubMed Central

    Foreman, P. A.

    1995-01-01

    Chronic neurogenous pain is often an extremely difficult condition to manage. In the orofacial region, trauma from injury or dental procedures may lead to the development of severe neuralgic pains and major distress to the patient. Clinical and experimental evidence suggests that the use of adequate preemptive regional anesthesia, systemic analgesia, and the avoidance of repeated, painful stimuli may reduce the incidence of this problem. PMID:8934952

  12. Standing worsens cognitive functions in patients with neurogenic orthostatic hypotension.

    PubMed

    Poda, R; Guaraldi, P; Solieri, L; Calandra-Buonaura, G; Marano, G; Gallassi, R; Cortelli, P

    2012-04-01

    In previous studies, addressing the association between orthostatic hypotension and cognitive decline, patients underwent neuropsychological evaluation in sitting position, and blood pressure values and cognition were not measured concurrently. Furthermore, no studies assessed the acute effects of orthostatic hypotension on cognitive performances. The aim of our study was to evaluate the effect of a documented fall in systolic blood pressure (SBP) of at least 20 mmHg on a battery of cognitive tests in patients with neurogenic orthostatic hypotension. Ten consecutive patients with neurogenic orthostatic hypotension, normal brain imaging, and a normal Mini Mental State Examination in supine position were enrolled in the study. Patients underwent a detailed neuropsychological assessment (Brief Mental Deterioration battery and computerized tests) over two test sessions: the first while tilted to an angle able to cause a fall of at least 20 mmHg in SBP; the second while supine, after 30 min of rest. Parallel forms of the tests were presented on each testing session. Patients scored significantly worse in the visual search test, analogies test, immediate visual memory, and the measure of global cognitive functioning of Brief Mental Deterioration battery during the orthostatic challenge compared to the supine position. Orthostatic hypotension was associated with a significant worsening of cognitive performances, affecting both global cognitive functioning and specific tasks, mainly exploring executive functions. The assessment of cognitive function in patients with neurogenic orthostatic hypotension should be performed considering the body's position of the subject.

  13. The pre-vertebrate origins of neurogenic placodes.

    PubMed

    Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N; Winchell, Christopher J; Hudson, Clare; Kamata, Kaori; Nakagawa, Masashi; Tsuda, Motoyuki; Kusakabe, Takehiro G; Levine, Michael

    2015-08-27

    The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates. PMID:26258298

  14. In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope

    PubMed Central

    Bojić, Tijana; Perović, Vladimir R.; Glišić, Sanja

    2016-01-01

    Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment. PMID:26834545

  15. Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging

    PubMed Central

    Gebara, Elias; Sultan, Sebastien; Kocher-Braissant, Jacqueline; Toni, Nicolas

    2013-01-01

    Adult hippocampal neurogenesis results in the formation of new neurons and is a process of brain plasticity involved in learning and memory. The proliferation of adult neural stem or progenitor cells is regulated by several extrinsic factors such as experience, disease or aging and intrinsic factors originating from the neurogenic niche. Microglia is very abundant in the dentate gyrus (DG) and increasing evidence indicates that these cells mediate the inflammation-induced reduction in neurogenesis. However, the role of microglia in neurogenesis in physiological conditions remains poorly understood. In this study, we monitored microglia and the proliferation of adult hippocampal stem/progenitor cells in physiological conditions known to increase or decrease adult neurogenesis, voluntary running and aging respectively. We found that the number of microglia in the DG was strongly inversely correlated with the number of stem/progenitor cells and cell proliferation in the granule cell layer. Accordingly, co-cultures of decreasing neural progenitor/glia ratio showed that microglia but not astroglia reduced the number of progenitor cells. Together, these results suggest that microglia inhibits the proliferation of neural stem/progenitor cells despite the absence of inflammatory stimulus. PMID:23970848

  16. Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis.

    PubMed

    Garthe, Alexander; Roeder, Ingo; Kempermann, Gerd

    2016-02-01

    We here show that living in a stimulus-rich environment (ENR) improves water maze learning with respect to specific key indicators that in previous loss-of-function experiments have been shown to rely on adult hippocampal neurogenesis. Analyzing the strategies employed by mice to locate the hidden platform in the water maze revealed that ENR facilitated task acquisition by increasing the probability to use effective search strategies. ENR also enhanced the animals' behavioral flexibility, when the escape platform was moved to a new location. Treatment with temozolomide, which is known to reduce adult neurogenesis, abolished the effects of ENR on both acquisition and flexibility, while leaving other aspects of water maze learning untouched. These characteristic effects and interdependencies were not seen in parallel experiments with voluntary wheel running (RUN), a second pro-neurogenic behavioral stimulus. Since the histological assessment of adult neurogenesis is by necessity an end-point measure, the levels of neurogenesis over the course of the experiment can only be inferred and the present study focused on behavioral parameters as analytical endpoints. Although the correlation of physical activity with precursor cell proliferation and of learning and the survival of new neurons is well established, how the specific functional effects described here relate to dynamic changes in the stem cell niche remains to be addressed. Nevertheless, our findings support the hypothesis that adult neurogenesis is a critical mechanism underlying the beneficial effects of leading an active live, rich in experiences.

  17. Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging.

    PubMed

    Gebara, Elias; Sultan, Sebastien; Kocher-Braissant, Jacqueline; Toni, Nicolas

    2013-01-01

    Adult hippocampal neurogenesis results in the formation of new neurons and is a process of brain plasticity involved in learning and memory. The proliferation of adult neural stem or progenitor cells is regulated by several extrinsic factors such as experience, disease or aging and intrinsic factors originating from the neurogenic niche. Microglia is very abundant in the dentate gyrus (DG) and increasing evidence indicates that these cells mediate the inflammation-induced reduction in neurogenesis. However, the role of microglia in neurogenesis in physiological conditions remains poorly understood. In this study, we monitored microglia and the proliferation of adult hippocampal stem/progenitor cells in physiological conditions known to increase or decrease adult neurogenesis, voluntary running and aging respectively. We found that the number of microglia in the DG was strongly inversely correlated with the number of stem/progenitor cells and cell proliferation in the granule cell layer. Accordingly, co-cultures of decreasing neural progenitor/glia ratio showed that microglia but not astroglia reduced the number of progenitor cells. Together, these results suggest that microglia inhibits the proliferation of neural stem/progenitor cells despite the absence of inflammatory stimulus.

  18. Distinct Effects of Chronic Dopaminergic Stimulation on Hippocampal Neurogenesis and Striatal Doublecortin Expression in Adult Mice

    PubMed Central

    Salvi, Rachele; Steigleder, Tobias; Schlachetzki, Johannes C. M.; Waldmann, Elisabeth; Schwab, Stefan; Winner, Beate; Winkler, Jürgen; Kohl, Zacharias

    2016-01-01

    While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ), recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g., the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA) receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX), and Ropinirole (ROP), on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2′-deoxyuridine (BrdU) a proliferation paradigm was performed in which two BrdU injections (100 mg/kg) were applied intraperitoneally within 12 h after a 14-days-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS)-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and Neuronal Nuclei (NeuN) 32 days after the last of five BrdU injections (50 mg/kg) applied at the beginning of 14-days DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX) in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX+ neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active

  19. A review of prospective Clinical Trials for neurogenic bladder: The place of surgery, experimental techniques and devices

    PubMed Central

    Braschi, Emmanuel; Lavelle, John

    2014-01-01

    Introduction The neurogenic urinary bladder has been known for at least 30 years now and the concepts behind it are continuously evolving, but there is actually not much work that has been done to accumulate solid clinical evidence in this field. We review the surgical and experimental techniques used in the management of this condition. Material and methods To achieve our goal, we performed Internet searches using the same search string: Urinary bladder, neurogenic. In each case, the search was limited to clinical trial, subjects were human and the language was English. After duplicate removal, we obtained a final number of 580 papers. Data was extracted from each paper into a database file and was analyzed separately for adult and pediatric populations. Results A total of 70 full text papers were reviewed and analyzed according to the previously mentioned algorithm. The first prospective, randomized surgical trials were published less than 20 years ago, starting with 1994, and the number of papers published each year since then has remained in the range of 1–3. The oldest prospective clinical trial for this indication dates back to 1975. The total number of patients included in surgical trials is 3453, out of which 59% are males. The papers include a total of 369 children (21.2%), essentially looking at all the techniques that are also used in adults. Conclusions There is still a lot of work to be done in order to obtain a significant level of evidence in the field of surgical procedures used in neurogenic bladder patients. PMID:25247086

  20. Testicular Niche Required for Human Spermatogonial Stem Cell Expansion

    PubMed Central

    Smith, James F.; Yango, Pamela; Altman, Eran; Choudhry, Shweta; Poelzl, Andrea; Zamah, Alberuni M.; Rosen, Mitchell; Klatsky, Peter C.

    2014-01-01

    Prepubertal boys treated with high-dose chemotherapy do not have an established means of fertility preservation because no established in vitro technique exists to expand and mature purified spermatogonial stem cells (SSCs) to functional sperm in humans. In this study, we define and characterize the unique testicular cellular niche required for SSC expansion using testicular tissues from men with normal spermatogenesis. Highly purified SSCs and testicular somatic cells were isolated by fluorescence-activated cell sorting using SSEA-4 and THY1 as markers of SSCs and somatic cells. Cells were cultured on various established niches to assess their role in SSC expansion in a defined somatic cellular niche. Of all the niches examined, cells in the SSEA-4 population exclusively bound to adult testicular stromal cells, established colonies, and expanded. Further characterization of these testicular stromal cells revealed distinct mesenchymal markers and the ability to undergo differentiation along the mesenchymal lineage, supporting a testicular multipotent stromal cell origin. In vitro human SSC expansion requires a unique niche provided exclusively by testicular multipotent stromal cells with mesenchymal properties. These findings provide an important foundation for developing methods of inducing SSC growth and maturation in prepubertal testicular tissue, essential to enabling fertility preservation for these boys. PMID:25038247

  1. Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease.

    PubMed

    Awad, Richard A

    2011-12-14

    Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel

  2. Improved Predictions of the Geographic Distribution of Invasive Plants Using Climatic Niche Models.

    PubMed

    Ramírez-Albores, Jorge E; Bustamante, Ramiro O; Badano, Ernesto I

    2016-01-01

    Climatic niche models for invasive plants are usually constructed with occurrence records taken from literature and collections. Because these data neither discriminate among life-cycle stages of plants (adult or juvenile) nor the origin of individuals (naturally established or man-planted), the resulting models may mispredict the distribution ranges of these species. We propose that more accurate predictions could be obtained by modelling climatic niches with data of naturally established individuals, particularly with occurrence records of juvenile plants because this would restrict the predictions of models to those sites where climatic conditions allow the recruitment of the species. To test this proposal, we focused on the Peruvian peppertree (Schinus molle), a South American species that has largely invaded Mexico. Three climatic niche models were constructed for this species using high-resolution dataset gathered in the field. The first model included all occurrence records, irrespective of the life-cycle stage or origin of peppertrees (generalized niche model). The second model only included occurrence records of naturally established mature individuals (adult niche model), while the third model was constructed with occurrence records of naturally established juvenile plants (regeneration niche model). When models were compared, the generalized climatic niche model predicted the presence of peppertrees in sites located farther beyond the climatic thresholds that naturally established individuals can tolerate, suggesting that human activities influence the distribution of this invasive species. The adult and regeneration climatic niche models concurred in their predictions about the distribution of peppertrees, suggesting that naturally established adult trees only occur in sites where climatic conditions allow the recruitment of juvenile stages. These results support the proposal that climatic niches of invasive plants should be modelled with data of

  3. Improved Predictions of the Geographic Distribution of Invasive Plants Using Climatic Niche Models

    PubMed Central

    Ramírez-Albores, Jorge E.; Bustamante, Ramiro O.

    2016-01-01

    Climatic niche models for invasive plants are usually constructed with occurrence records taken from literature and collections. Because these data neither discriminate among life-cycle stages of plants (adult or juvenile) nor the origin of individuals (naturally established or man-planted), the resulting models may mispredict the distribution ranges of these species. We propose that more accurate predictions could be obtained by modelling climatic niches with data of naturally established individuals, particularly with occurrence records of juvenile plants because this would restrict the predictions of models to those sites where climatic conditions allow the recruitment of the species. To test this proposal, we focused on the Peruvian peppertree (Schinus molle), a South American species that has largely invaded Mexico. Three climatic niche models were constructed for this species using high-resolution dataset gathered in the field. The first model included all occurrence records, irrespective of the life-cycle stage or origin of peppertrees (generalized niche model). The second model only included occurrence records of naturally established mature individuals (adult niche model), while the third model was constructed with occurrence records of naturally established juvenile plants (regeneration niche model). When models were compared, the generalized climatic niche model predicted the presence of peppertrees in sites located farther beyond the climatic thresholds that naturally established individuals can tolerate, suggesting that human activities influence the distribution of this invasive species. The adult and regeneration climatic niche models concurred in their predictions about the distribution of peppertrees, suggesting that naturally established adult trees only occur in sites where climatic conditions allow the recruitment of juvenile stages. These results support the proposal that climatic niches of invasive plants should be modelled with data of

  4. Improved Predictions of the Geographic Distribution of Invasive Plants Using Climatic Niche Models.

    PubMed

    Ramírez-Albores, Jorge E; Bustamante, Ramiro O; Badano, Ernesto I

    2016-01-01

    Climatic niche models for invasive plants are usually constructed with occurrence records taken from literature and collections. Because these data neither discriminate among life-cycle stages of plants (adult or juvenile) nor the origin of individuals (naturally established or man-planted), the resulting models may mispredict the distribution ranges of these species. We propose that more accurate predictions could be obtained by modelling climatic niches with data of naturally established individuals, particularly with occurrence records of juvenile plants because this would restrict the predictions of models to those sites where climatic conditions allow the recruitment of the species. To test this proposal, we focused on the Peruvian peppertree (Schinus molle), a South American species that has largely invaded Mexico. Three climatic niche models were constructed for this species using high-resolution dataset gathered in the field. The first model included all occurrence records, irrespective of the life-cycle stage or origin of peppertrees (generalized niche model). The second model only included occurrence records of naturally established mature individuals (adult niche model), while the third model was constructed with occurrence records of naturally established juvenile plants (regeneration niche model). When models were compared, the generalized climatic niche model predicted the presence of peppertrees in sites located farther beyond the climatic thresholds that naturally established individuals can tolerate, suggesting that human activities influence the distribution of this invasive species. The adult and regeneration climatic niche models concurred in their predictions about the distribution of peppertrees, suggesting that naturally established adult trees only occur in sites where climatic conditions allow the recruitment of juvenile stages. These results support the proposal that climatic niches of invasive plants should be modelled with data of

  5. Niche differentiation between diploid and hexaploid Aster amellus.

    PubMed

    Raabová, Jana; Fischer, Markus; Münzbergová, Zuzana

    2008-12-01

    The maintenance of separated diploid and polyploid populations within a contact zone is possible due to both prezygotic and postzygotic isolation mechanisms. Niche differentiation between two cytotypes may be an important prezygotic isolating mechanism and can be studied using reciprocal transplant experiments. We investigated niche differentiation between diploid and hexaploid Aster amellus in their contact zone in the Czech Republic. Diploid populations are confined to habitats with low productivity, whereas hexaploid populations occur in habitats with both low and high productivity. Thus, we chose three diploid populations and six hexaploid populations, three in each of the two different habitat types. We analyzed habitat characteristics and carried out reciprocal transplant experiments in the field using both seeds and adult plants. Sites of diploid and hexaploid populations differed significantly in vegetation and soil properties. The mean number of juveniles was higher at sites of home ploidy level than at sites of foreign ploidy level, suggesting niche differentiation between the two cytotypes. On the other hand, transplanted adult plants survived at all sites and juvenile plants were able to establish at some sites of the foreign cytotype. Furthermore, the mean number of juveniles, survival, and flowering percentages were higher at home sites than at foreign sites, indicating local adaptation. We conclude that niche differentiation between the two cytotypes and local adaptation within each cytotype may contribute to the maintenance of diploid and hexaploid populations of A. amellus in their contact zone. Moreover, further factors, such as differences in flowering phenology and exclusion of minority cytotypes, should also be considered.

  6. Re-examining "temporal niche".

    PubMed

    Smarr, Benjamin L; Schwartz, Michael D; Wotus, Cheryl; de la Iglesia, Horacio O

    2013-07-01

    The circadian system temporally organizes physiology and behavior throughout the 24-h day. At the core of this organization lies a network of multiple circadian oscillators located within the central nervous system as well as in virtually every peripheral organ. These oscillators define a 24-h temporal landscape of mutually interacting circadian rhythms that is known as the temporal niche of a species. This temporal niche is constituted by the collective phases of all biological rhythms emerging from this multi-oscillatory system. We review evidence showing that under different environmental conditions, this system can adopt different harmonic configurations. Thus, the classic chronobiological approach of searching for "the" circadian phase of an animal-typically by studying circadian rhythms of locomotor activity-represents a narrow look into the circadian system of an animal. We propose that the study of hormonal rhythms may lead to a more insightful assessment of a species' temporal niche.

  7. Ecological niche of Legionella pneumophila

    SciTech Connect

    Fliermans, C.B.

    1983-01-01

    This paper discusses the ecological niches, relationships and controls of Legionella derived from environmental sources. Only as clinical cases and studies relate directly to the ecological understanding of the bacterium will they be discussed. This review seeks to separate the ecological parameters associated with Legionella that are often incorporated into the medical literature as well as to highlight specific ecological studies. A series of ecological studies demonstrates the niches of Legionella, the ecological parameters that allow the bacterium to survive, grow and to be disseminated. Relationships among given habitats are explored along with biological relationships within a given habitat.

  8. The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis.

    PubMed

    Ortega-Martínez, Sylvia; Trejo, José L

    2015-02-15

    The relevance of adult neurogenesis in hippocampal function is well documented, as is the potential impact stress has on the adult neurogenic niche. Adult born neurons are generated from neural precursors in the dentate gyrus (DG), although the point in postnatal development that these cell precursors originate is not known. This is particularly relevant if we consider the effects stress may have on the development of neural precursors, and whether such effects on adult neurogenesis and behavior may persist in the long-term. We have analyzed the proportion of neural precursors in the adult murine hippocampus born on specific days during postnatal development using a dual birth-dating analysis, and we assessed their sensitivity to dexamethasone (DEX) on the peak day of cell generation. We also studied the consequences of postnatal DEX administration on adult hippocampal-dependent behavior. Postnatal day 6 (P6) is a preferred period for proliferating neural stem cells (NSCs) to become the precursors that remain in a proliferative state throughout adulthood. This window is independent of gender, the cell's location in the DG granule cell layer or their rostro-caudal position. DEX administration at P6 reduces the size of the adult NSC pool in the DG, which is correlated with poor learning/memory capacity and increased anxiety-like behavior. These results indicate that aNSCs are generated non-uniformly during postnatal development, with peak generation on day P6, and that stress receptor activation during the key period of postnatal NSC generation has a profound impact on both adult hippocampal neurogenesis and behavior.

  9. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.

    PubMed

    Scola, R H; Werneck, L C; Iwamoto, F M; Ribas, L C; Raskin, S; Correa Neto, Y

    2001-06-01

    We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  10. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    PubMed

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  11. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    PubMed Central

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions. PMID:26634814

  12. A One Year Prospective Study of Neurogenic Stuttering Following Stroke: Incidence and Co-Occurring Disorders

    ERIC Educational Resources Information Center

    Theys, C.; van Wieringen, A.; Sunaert, S.; Thijs, V.; De Nil, L. F.

    2011-01-01

    In this prospective study, data on incidence, stuttering characteristics, co-occurring speech disorders, and recovery of neurogenic stuttering in a large sample of stroke participants were assessed. Following stroke onset, 17 of 319 participants (5.3%; 95% CI, 3.2-8.3) met the criteria for neurogenic stuttering. Stuttering persisted in at least…

  13. A NICHE FOR ISOTOPIC ECOLOGY

    EPA Science Inventory

    Fifty years ago, GE Hutchinson defined the ecological niche as a hypervolume in n-dimensional space with environmental variables as axes. Ecologists have recently developed renewed interest in the concept, and technological advances now allow us to use stable isotope analyses to ...

  14. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension

    PubMed Central

    Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R

    2015-01-01

    Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension. PMID:25900825

  15. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension.

    PubMed

    Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R

    2015-07-15

    Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension. PMID:25900825

  16. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    PubMed

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs.

  17. Concise review: The plasticity of stem cell niches: a general property behind tissue homeostasis and repair.

    PubMed

    Rojas-Ríos, Patricia; González-Reyes, Acaimo

    2014-04-01

    Stem cell activity is tightly regulated during development and in adult tissues through the combined action of local and systemic effectors. While stem cells and their microenvironments are capable of sustaining homeostasis in normal physiological circumstances, they also provide host tissues with a remarkable plasticity to respond to perturbations. Here, we review recent discoveries that shed light on the adaptive response of niches to systemic signals and aging, and on the ability of niches to modulate signaling upon local perturbations. These characteristics of stem cells and their niches give organs an essential advantage to deal with aging, injury or pathological conditions.

  18. [Neurological Signs and Symptoms of True Neurogenic Thoracic Outlet Syndrome].

    PubMed

    Higashihara, Mana; Konoeda, Fumie; Sonoo, Masahiro

    2016-05-01

    Thoracic outlet syndrome (TOS) is a well-known disorder, but many aspects of its pathology, including its definition, has been disputed. True neurogenic TOS (TN-TOS) is a rare but well-defined clinical condition. TN-TOS results from the compression of the C8/T1 roots (dominant for the T1 root) or the proximal lower trunk of the brachial plexus by a fibrous band. The band extends from the first rib to either the tip of an elongated C7 transverse process or a rudimentary cervical rib. The most common presenting symptoms of TN-TOS are insidious-onset atrophy and weakness of the intrinsic hand muscles, predominantly in the thenar eminence and radial digit flexors. Nerve conduction studies demonstrate pathognomonic findings: severely attenuated compound muscle action potential of the abductor pollicis brevis muscle, and usually, loss of the sensory nerve action potential of the medial antebrachial cutaneous nerve. Numbness and sensory loss are typically observed, mainly in the medial forearm, although they are usually mild, and may be absent in some patients. Severe pain or paresthesia proximal to the elbow is not observed. The classical concept of TOS underlie nonspecific neurogenic TOS. It has been primarily diagnosed using provocative maneuvers. However, there is controversy regarding its pathological conceptualization and existence, as objective evidence of the disease is still lacking. PMID:27156505

  19. Neurogenic gene regulatory pathways in the sea urchin embryo.

    PubMed

    Wei, Zheng; Angerer, Lynne M; Angerer, Robert C

    2016-01-15

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo.

  20. Neurogenic gene regulatory pathways in the sea urchin embryo.

    PubMed

    Wei, Zheng; Angerer, Lynne M; Angerer, Robert C

    2016-01-15

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. PMID:26657764

  1. From network structure to network reorganization: implications for adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Schneider-Mizell, Casey M.; Parent, Jack M.; Ben-Jacob, Eshel; Zochowski, Michal R.; Sander, Leonard M.

    2010-12-01

    Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells.

  2. Valproic acid, a histone deacetylase inhibitor, decreases proliferation of and induces specific neurogenic differentiation of canine adipose tissue-derived stem cells.

    PubMed

    Kurihara, Yasuhiro; Suzuki, Takehito; Sakaue, Motoharu; Murayama, Ohoshi; Miyazaki, Yoko; Onuki, Atsushi; Aoki, Takuma; Saito, Miyoko; Fujii, Yoko; Hisasue, Masaharu; Tanaka, Kazuaki; Takizawa, Tatsuya

    2014-01-01

    Adipose tissue-derived stem cells (ADSCs) isolated from adult tissue have pluripotent differentiation and self-renewal capability. The tissue source of ADSCs can be obtained in large quantities and with low risks, thus highlighting the advantages of ADSCs in clinical applications. Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to affect ADSC differentiation in mice and rats; however, few studies have been performed on dogs. We aimed to examine the in vitro effect of VPA on canine ADSCs. Three days of pretreatment with VPA decreased the proliferation of ADSCs in a dose-dependent manner; VPA concentrations of 4 mM and above inhibited the proliferation of ADSCs. In parallel, VPA increased p16 and p21 mRNA expression, suggesting that VPA attenuated the proliferative activity of ADSCs by activating p16 and p21. Furthermore, the effects of VPA on adipogenic, osteogenic or neurogenic differentiation were investigated morphologically. VPA pretreatment markedly promoted neurogenic differentiation, but suppressed the accumulation of lipid droplets and calcium depositions. These modifications of ADSCs by VPA were associated with a particular gene expression profile, viz., an increase in neuronal markers, that is, NSE, TUBB3 and MAP2, a decrease in the adipogenic marker, LPL, but no changes in osteogenic markers, as estimated by reverse transcription-PCR analysis. These results suggested that VPA is a specific inducer of neurogenic differentiation of canine ADSCs and is a useful tool for studying the interaction between chromatin structure and cell fate determination.

  3. ECM-Regulator timp Is Required for Stem Cell Niche Organization and Cyst Production in the Drosophila Ovary

    PubMed Central

    Pearson, John R.; Zurita, Federico; Tomás-Gallardo, Laura; Díaz-Torres, Alfonsa; Díaz de la Loza, María del Carmen; Franze, Kristian; Martín-Bermudo, María D.; González-Reyes, Acaimo

    2016-01-01

    The extracellular matrix (ECM) is a pivotal component adult tissues and of many tissue-specific stem cell niches. It provides structural support and regulates niche signaling during tissue maintenance and regeneration. In many tissues, ECM remodeling depends on the regulation of MMP (matrix metalloproteinase) activity by inhibitory TIMP (tissue inhibitors of metalloproteinases) proteins. Here, we report that the only Drosophila timp gene is required for maintaining the normal organization and function of the germline stem cell niche in adult females. timp mutant ovaries show reduced levels of both Drosophila Collagen IV α chains. In addition, tissue stiffness and the cellular organization of the ovarian niche are affected in timp mutants. Finally, loss of timp impairs the ability of the germline stem cell niche to generate new cysts. Our results demonstrating a crucial role for timp in tissue organization and gamete production thus provide a link between the regulation of ECM metabolism and tissue homeostasis. PMID:26808525

  4. Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior.

    PubMed

    Guha, Suman K; Tillu, Rucha; Sood, Ankit; Patgaonkar, Mandar; Nanavaty, Ishira N; Sengupta, Arjun; Sharma, Shobhona; Vaidya, Vidita A; Pathak, Sulabha

    2014-11-01

    Cerebral malaria is associated with cerebrovascular damage and neurological sequelae. However, the neurological consequences of uncomplicated malaria, the most prevalent form of the disease, remain uninvestigated. Here, using a mild malaria model, we show that a single Plasmodium chabaudi adami infection in adult mice induces neuroinflammation, neurogenic, and behavioral changes in the absence of a blood-brain barrier breach. Using cytokine arrays we show that the infection induces differential serum and brain cytokine profiles, both at peak parasitemia and 15days post-parasite clearance. At the peak of infection, along with the serum, the brain also exhibited a definitive pro-inflammatory cytokine profile, and gene expression analysis revealed that pro-inflammatory cytokines were also produced locally in the hippocampus, an adult neurogenic niche. Hippocampal microglia numbers were enhanced, and we noted a shift to an activated profile at this time point, accompanied by a striking redistribution of the microglia to the subgranular zone adjacent to hippocampal neuronal progenitors. In the hippocampus, a distinct decline in progenitor turnover and survival was observed at peak parasitemia, accompanied by a shift from neuronal to glial fate specification. Studies in transgenic Nestin-GFP reporter mice demonstrated a decline in the Nestin-GFP(+)/GFAP(+) quiescent neural stem cell pool at peak parasitemia. Although these cellular changes reverted to normal 15days post-parasite clearance, specific brain cytokines continued to exhibit dysregulation. Behavioral analysis revealed selective deficits in social and anxiety-like behaviors, with no change observed in locomotor, cognitive, and depression-like behaviors, with a return to baseline at recovery. Collectively, these findings indicate that even a single episode of mild malaria results in alterations of the brain cytokine profile, causes specific behavioral dysfunction, is accompanied by hippocampal microglial

  5. Evolution of climate niches in European mammals?

    PubMed Central

    Dormann, Carsten F.; Gruber, Bernd; Winter, Marten; Herrmann, Dirk

    2010-01-01

    Our ability to predict consequences of climate change is severely impaired by the lack of knowledge on the ability of species to adapt to changing environmental conditions. We used distribution data for 140 mammal species in Europe, together with data on climate, land cover and topography, to derive a statistical description of their realized climate niche. We then compared climate niche overlap of pairs of species, selected on the basis of phylogenetic information. In contrast to expectations, related species were not similar in their climate niche. Rather, even species pairs that had a common ancestor less than 1 Ma already display very high climate niche distances. We interpret our finding as a strong interspecific competitive constraint on the realized niche, rather than a rapid evolution of the fundamental niche. If correct, our results imply a very limited usefulness of climate niche models for the prediction of future mammal distributions. PMID:19828492

  6. Evolution of climate niches in European mammals?

    PubMed

    Dormann, Carsten F; Gruber, Bernd; Winter, Marten; Herrmann, Dirk

    2010-04-23

    Our ability to predict consequences of climate change is severely impaired by the lack of knowledge on the ability of species to adapt to changing environmental conditions. We used distribution data for 140 mammal species in Europe, together with data on climate, land cover and topography, to derive a statistical description of their realized climate niche. We then compared climate niche overlap of pairs of species, selected on the basis of phylogenetic information. In contrast to expectations, related species were not similar in their climate niche. Rather, even species pairs that had a common ancestor less than 1 Ma already display very high climate niche distances. We interpret our finding as a strong interspecific competitive constraint on the realized niche, rather than a rapid evolution of the fundamental niche. If correct, our results imply a very limited usefulness of climate niche models for the prediction of future mammal distributions.

  7. Morphological and niche divergence of pinyon pines.

    PubMed

    Ortiz-Medrano, Alejandra; Scantlebury, Daniel Patrick; Vázquez-Lobo, Alejandra; Mastretta-Yanes, Alicia; Piñero, Daniel

    2016-05-01

    The environmental variables that define a species ecological niche should be associated with the evolutionary patterns present in the adaptations that resulted from living in these conditions. Thus, when comparing across species, we can expect to find an association between phylogenetically independent phenotypic characters and ecological niche evolution. Few studies have evaluated how organismal phenotypes might mirror patterns of niche evolution if these phenotypes reflect adaptations. Doing so could contribute on the understanding of the origin and maintenance of phenotypic diversity observed in nature. Here, we show the pattern of niche evolution of the pinyon pine lineage (Pinus subsection Cembroides); then, we suggest morphological adaptations possibly related to niche divergence, and finally, we test for correlation between ecological niche and morphology. We demonstrate that niche divergence is the general pattern within the clade and that it is positively correlated with adaptation. PMID:27092235

  8. Human Niche Construction and Hydrology

    NASA Astrophysics Data System (ADS)

    Ertsen, Maurits

    2014-05-01

    The poster will introduce Human Niche Construction Theory to clarify the capacity of organisms to modify their environment and thereby influence their own and other species' evolution. HNC allows building a recursive relationship between long-term human actions and landscape modification. Discussing the concept will also allow studying why we should understand societal collapse in new ways and whether policies towards sustainability will have a potential for success.

  9. Phosphatase and actin regulator 4 is associated with intermediate filaments in adult neural stem cells and their progenitor astrocytes.

    PubMed

    Cho, Hyo Min; Kim, Joo Yeon; Kim, Hyun; Sun, Woong

    2014-10-01

    Phosphatase and actin regulator 4 (Phactr4) is a newly discovered protein that inhibits protein phosphatase 1 and shows actin-binding activity. We previously found that Phactr4 is expressed in the neurogenic niche in adult mice, although its precise subcellular localization and possible function in neural stem cells (NSCs) is not yet understood. Here, we show that Phactr4 formed punctiform clusters in the cytosol of subventricular zone-derived adult NSCs and their progeny in vitro. These Phactr4 signals were not associated with F-actin fibers but were closely associated with intermediate filaments such as nestin and glial fibrillary acidic protein (GFAP) fibers. Direct binding of Phactr4 with nestin and GFAP filaments was demonstrated using Duolink protein interaction analyses and immunoprecipitation assays. Interestingly, when nestin fibers were de-polymerized during the mitosis or by the phosphatase inhibitor, Phactr4 appeared to be dissociated from nestin, suggesting that their protein interaction is regulated by the protein phosphorylation. These results suggest that Phactr4 forms functional associations with intermediate filament networks in adult NSCs.

  10. How is the rate of climatic-niche evolution related to climatic-niche breadth?

    PubMed

    Fisher-Reid, M Caitlin; Kozak, Kenneth H; Wiens, John J

    2012-12-01

    The rate of climatic-niche evolution is important to many research areas in ecology, evolution, and conservation biology, including responses of species to global climate change, spread of invasive species, speciation, biogeography, and patterns of species richness. Previous studies have implied that clades with higher rates of climatic-niche evolution among species should have species with narrower niche breadths, but there is also evidence suggesting the opposite pattern. However, the relationships between rate and breadth have not been explicitly analyzed. Here, we examine the relationships between the rate of climatic-niche evolution and climatic-niche breadth using phylogenetic and climatic data for 250 species in the salamander family Plethodontidae, a group showing considerable variation in both rates of climatic-niche evolution and climatic-niche breadths. Contrary to some expectations, we find no general relationship between climatic-niche breadth and the rate of climatic-niche evolution. Climatic-niche breadths for some ecologically important climatic variables considered separately (temperature seasonality and annual precipitation) do show significant relationships with the rate of climatic-niche evolution, but rates are faster in clades in which species have broader (not narrower) niche breadths. In summary, our results show that narrower niche breadths are not necessarily associated with faster rates of niche evolution.

  11. Persistent neurogenic bladder dysfunction due to infantile botulism.

    PubMed

    Breinbjerg, Anders; Rittig, Søren; Kamperis, Konstantinos

    2014-01-13

    We present a child, 5 months of age, diagnosed with infantile botulism, showing the signs of neurogenic bladder dysfunction. The patient presented with progressive muscle weakness, hypotonia, suckling and swallowing problems and absent peripheral reflexes at clinical examination. Botulinum neurotoxin type A was detected in her serum, confirming the diagnosis. Starting at day 6, the girl presented with a urinary retention initially necessitating free bladder drainage and subsequently intermittent catheterisation. After 6 weeks in intensive care, the patient recovered but the bladder underactivity persisted. Four months following recovery, a urodynamic evaluation was performed, showing a near normal detrusor activity and normal bladder emptying, and the catheterisation was ceased. At 6 months, the girl was diagnosed with a urinary tract infection and bladder emptying problems, which persisted, and clean intermittent catheterisation was started. The final urodynamic evaluation, a year and a half after her initial presentation, revealed a normal detrusor activity and an adequate bladder emptying.

  12. Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.

    PubMed

    Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T

    2015-05-01

    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy.

  13. Evolution of niche width and adaptive diversification.

    PubMed

    Ackermann, Martin; Doebeli, Michael

    2004-12-01

    Theoretical models suggest that resource competition can lead to the adaptive splitting of consumer populations into diverging lineages, that is, to adaptive diversification. In general, diversification is likely if consumers use only a narrow range of resources and thus have a small niche width. Here we use analytical and numerical methods to study the consequences for diversification if the niche width itself evolves. We found that the evolutionary outcome depends on the inherent costs or benefits of widening the niche. If widening the niche did not have costs in terms of overall resource uptake, then the consumer evolved a niche that was wide enough for disruptive selection on the niche position to vanish; adaptive diversification was no longer observed. However, if widening the niche was costly, then the niche widths remained relatively narrow, allowing for adaptive diversification in niche position. Adaptive diversification and speciation resulting from competition for a broadly distributed resource is thus likely if the niche width is fixed and relatively narrow or free to evolve but subject to costs. These results refine the conditions for adaptive diversification due to competition and formulate them in a way that might be more amenable for experimental investigations. PMID:15696740

  14. Diversity, dilemmas, and monopolies of niche construction.

    PubMed

    Krakauer, David C; Page, Karen M; Erwin, Douglas H

    2009-01-01

    The behavior of organisms can contribute to the transformation of their environments. When organismal impacts on the environment feed back to influence organismal density, viability, fertility, or persistence, the environment can be construed as an extension of the organism. This process of fitness-enhancing environmental transformation has been called niche construction. We focus on the relationship of niche construction with species or strain diversity and on the variability of investment in niche construction versus reproduction. We demonstrate a fundamental dilemma of niche construction, whereby the construction of a shared resource leads to a tragedy of the commons, with competition tending to eliminate niche construction strategies. The ability to monopolize a niche, either through spatial proximity or through preferential exploitation, can stabilize niche construction and promote ecological coexistence among polymorphic constructors. We consider both sympatric and allopatric origins of niche construction. Under a variety of different construction mechanisms, variability in the investment in niche construction versus reproduction suggests reproductive altruism but is fully consistent with selfish behavior. We discuss the implications of niche-construction theory on the evolution of life cycles and development, behavioral plasticity, the division of labor, and long-term macroevolutionary trends.

  15. Phylogenetic conservatism of environmental niches in mammals.

    PubMed

    Cooper, Natalie; Freckleton, Rob P; Jetz, Walter

    2011-08-01

    Phylogenetic niche conservatism is the pattern where close relatives occupy similar niches, whereas distant relatives are more dissimilar. We suggest that niche conservatism will vary across clades in relation to their characteristics. Specifically, we investigate how conservatism of environmental niches varies among mammals according to their latitude, range size, body size and specialization. We use the Brownian rate parameter, σ(2), to measure the rate of evolution in key variables related to the ecological niche and define the more conserved group as the one with the slower rate of evolution. We find that tropical, small-ranged and specialized mammals have more conserved thermal niches than temperate, large-ranged or generalized mammals. Partitioning niche conservatism into its spatial and phylogenetic components, we find that spatial effects on niche variables are generally greater than phylogenetic effects. This suggests that recent evolution and dispersal have more influence on species' niches than more distant evolutionary events. These results have implications for our understanding of the role of niche conservatism in species richness patterns and for gauging the potential for species to adapt to global change.

  16. Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

    PubMed

    Fan, Yiping; Marcy, Guillaume; Lee, Eddy S M; Rozen, Steve; Mattar, Citra N Z; Waddington, Simon N; Goh, Eyleen L K; Choolani, Mahesh; Chan, Jerry K Y

    2014-01-01

    Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS) when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6%) over other sources (range of 0%-27.5%, p<0.004). Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

  17. Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury.

    PubMed

    Pati, Soumya; Muthuraju, Sangu; Hadi, Raisah Ab; Huat, Tee Jong; Singh, Shailja; Maletic-Savatic, Mirjana; Abdullah, Jafri Malin; Jaafar, Hasnan

    2016-01-01

    Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications. PMID:26763886

  18. Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice

    PubMed Central

    Marlatt, Michael W.; Lucassen, Paul J.; van Praag, Henriette

    2010-01-01

    Hippocampal neurogenesis can be regulated by extrinsic factors, such as exercise and antidepressants. While there is evidence that the serotonin re-uptake inhibitor (SSRI) fluoxetine (Prozac) enhances neurogenesis, the new dual serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine has not been evaluated in this context. In addition, it is unclear whether effects of antidepressants and running on cell genesis and behavior are of similar magnitude in mice. Here,we assessed neurogenesis and open field behavior in 2 month old female C57Bl/6 mice after 28 days of treatment with either fluoxetine (18 mg/kg), duloxetine (2, 6 or 18 mg/kg) or exercise. New cell survival, as measured by 5-bromo-2´-deoxyuridine (BrdU) labeled cells, was enhanced by 200% in the running group only. Both running and fluoxetine, but not duloxetine, increased the percentage of new cells that became neurons. In the open field test, animals treated with either drug spent less time in the center than controls and runners. In addition, fluoxetine treatment resulted in reduced locomotor activity. Together, these data not only show that the neurogenic response to exercise is much stronger than to antidepressants, but also imply a low likelihood that reported effects of these two drugs on anxiety are mediated by adult neurogenesis in C57Bl/6 mice. PMID:20381469

  19. Heated indoor swimming pools, infants, and the pathogenesis of adolescent idiopathic scoliosis: a neurogenic hypothesis

    PubMed Central

    2011-01-01

    Background In a case-control study a statistically significant association was recorded between the introduction of infants to heated indoor swimming pools and the development of adolescent idiopathic scoliosis (AIS). In this paper, a neurogenic hypothesis is formulated to explain how toxins produced by chlorine in such pools may act deleteriously on the infant's immature central nervous system, comprising brain and spinal cord, to produce the deformity of AIS. Presentation of the hypothesis Through vulnerability of the developing central nervous system to circulating toxins, and because of delayed epigenetic effects, the trunk deformity of AIS does not become evident until adolescence. In mature healthy swimmers using such pools, the circulating neurotoxins detected are chloroform, bromodichloromethane, dibromochloromethane, and bromoform. Cyanogen chloride and dichloroacetonitrile have also been detected. Testing the hypothesis In infants, the putative portals of entry to the blood could be dermal, oral, or respiratory; and entry of such circulating small molecules to the brain are via the blood-brain barrier, blood-cerebrospinal fluid barrier, and circumventricular organs. Barrier mechanisms of the developing brain differ from those of adult brain and have been linked to brain development. During the first 6 months of life cerebrospinal fluid contains higher concentrations of specific proteins relative to plasma, attributed to mechanisms continued from fetal brain development rather than immaturity. Implications of the hypothesis The hypothesis can be tested. If confirmed, there is potential to prevent some children from developing AIS. PMID:21975145

  20. Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche

    PubMed Central

    Wang, Su; Gao, Yuan; Song, Xiaoqing; Ma, Xing; Zhu, Xiujuan; Mao, Ying; Yang, Zhihao; Ni, Jianquan; Li, Hua; Malanowski, Kathryn E; Anoja, Perera; Park, Jungeun; Haug, Jeff; Xie, Ting

    2015-01-01

    Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche. DOI: http://dx.doi.org/10.7554/eLife.08174.001 PMID:26452202

  1. Human dental pulp stem cells with highly angiogenic and neurogenic potential for possible use in pulp regeneration.

    PubMed

    Nakashima, Misako; Iohara, Koichiro; Sugiyama, Masahiko

    2009-01-01

    Dental caries is a common public health problem, causing early loss of dental pulp and resultant tooth loss. Dental pulp has important functions to sustain teeth providing nutrient and oxygen supply, innervation, reactionary/reparative dentin formation and immune response. Regeneration of pulp is an unmet need in endodontic therapy, and angiogenesis/vasculogenesis and neurogenesis are critical for pulp regeneration. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. In this review, we introduce some stem cell subfractions, CD31(-)/CD146(-) SP cells and CD105(+) cells with high angiogenic and neurogenic potential, derived from human adult dental pulp tissue. Potential utility of these cells is addressed as a source of cells for treatment of cerebral and limb ischemia and pulp inflammation complete with angiogenesis and vasculogenesis.

  2. The regulatory niche of intestinal stem cells.

    PubMed

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders.

  3. The regulatory niche of intestinal stem cells.

    PubMed

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders. PMID:27060879

  4. A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action

    PubMed Central

    Chakravarty, Sumana; Maitra, Swati; Reddy, R Gajendra; Das, Tapatee; Jhelum, Priya; Kootar, Scherazad; Rajan, Wenson D.; Samanta, Anumita; Samineni, Ramesh; Pabbaraja, Srihari; Kernie, Steven G.; Mehta, Goverdhan; Kumar, Arvind

    2015-01-01

    In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds. PMID:26388493

  5. An Aminopeptidase in the Drosophila Testicular Niche Acts in Germline Stem Cell Maintenance and Spermatogonial Dedifferentiation.

    PubMed

    Lim, Cindy; Gandhi, Shiv; Biniossek, Martin L; Feng, Lijuan; Schilling, Oliver; Urban, Siniša; Chen, Xin

    2015-10-13

    Extrinsic cues from the niche are known to regulate adult stem cell self-renewal versus differentiation. Here, we report that an aminopeptidase Slamdance (Sda) acts in the Drosophila testicular niche to maintain germline stem cells (GSCs) and regulate progenitor germ cell dedifferentiation. Mutations in sda lead to dramatic testicular niche deterioration and stem cell loss. Recombinant Sda has specific aminopeptidase activity in vitro, and the in vivo function of Sda requires an intact aminopeptidase domain. Sda is required for accumulation of mature DE-cadherin, and overexpression of DE-cadherin rescues most sda mutant phenotypes, suggesting that DE-cadherin is an important target of Sda. Finally, Sda is both necessary and sufficient to promote dedifferentiation during aging and recovery from genetically manipulated depletion of GSCs. Together, our results suggest that a niche factor promotes both stem cell maintenance and progenitor cell dedifferentiation.

  6. An Aminopeptidase in the Drosophila Testicular Niche Acts in Germline Stem Cell Maintenance and Spermatogonial Dedifferentiation.

    PubMed

    Lim, Cindy; Gandhi, Shiv; Biniossek, Martin L; Feng, Lijuan; Schilling, Oliver; Urban, Siniša; Chen, Xin

    2015-10-13

    Extrinsic cues from the niche are known to regulate adult stem cell self-renewal versus differentiation. Here, we report that an aminopeptidase Slamdance (Sda) acts in the Drosophila testicular niche to maintain germline stem cells (GSCs) and regulate progenitor germ cell dedifferentiation. Mutations in sda lead to dramatic testicular niche deterioration and stem cell loss. Recombinant Sda has specific aminopeptidase activity in vitro, and the in vivo function of Sda requires an intact aminopeptidase domain. Sda is required for accumulation of mature DE-cadherin, and overexpression of DE-cadherin rescues most sda mutant phenotypes, suggesting that DE-cadherin is an important target of Sda. Finally, Sda is both necessary and sufficient to promote dedifferentiation during aging and recovery from genetically manipulated depletion of GSCs. Together, our results suggest that a niche factor promotes both stem cell maintenance and progenitor cell dedifferentiation. PMID:26440886

  7. Niche Applications of Irreversible Electroporation.

    PubMed

    Bhatia, Shivank S; Arya, Rahul; Narayanan, Govindarajan

    2015-09-01

    Irreversible electroporation (IRE) induces cell death by exposing it to high-voltage, low-energy DC current pulses. The mechanism of cell death and healing is a departure from the other existing technologies such as radiofrequency ablation, microwave ablation, and cryoablation. These thermal ablative technologies have several applications in oncology but have limitations that have also been established. IRE has shown promise to overcome some of these limitations and has enabled the use of an ablative technology in treating lesions close to the bile ducts and vasculature and in organs such as the pancreas. This review highlights some of the niche applications of IRE and the data so far.

  8. Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae).

    PubMed

    Gómez, Camila; Tenorio, Elkin A; Montoya, Paola; Cadena, Carlos Daniel

    2016-02-10

    Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour.

  9. Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae).

    PubMed

    Gómez, Camila; Tenorio, Elkin A; Montoya, Paola; Cadena, Carlos Daniel

    2016-02-10

    Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour. PMID:26865303

  10. An Adaptive Niching Genetic Algorithm using a niche size equalization mechanism

    NASA Astrophysics Data System (ADS)

    Nagata, Yuichi

    Niching GAs have been widely investigated to apply genetic algorithms (GAs) to multimodal function optimization problems. In this paper, we suggest a new niching GA that attempts to form niches, each consisting of an equal number of individuals. The proposed GA can be applied also to combinatorial optimization problems by defining a distance metric in the search space. We apply the proposed GA to the job-shop scheduling problem (JSP) and demonstrate that the proposed niching method enhances the ability to maintain niches and improve the performance of GAs.

  11. Target Article with Commentaries: Developmental Niche Construction

    ERIC Educational Resources Information Center

    Flynn, Emma G.; Laland, Kevin N.; Kendal, Rachel L.; Kendal, Jeremy R.

    2013-01-01

    Niche construction is the modification of components of the environment through an organism's activities. Humans modify their environments mainly through ontogenetic and cultural processes, and it is this reliance on learning, plasticity and culture that lends human niche construction a special potency. In this paper we aim to facilitate…

  12. Hutchinson's duality: the once and future niche.

    PubMed

    Colwell, Robert K; Rangel, Thiago F

    2009-11-17

    The duality between "niche" and "biotope" proposed by G. Evelyn Hutchinson provides a powerful way to conceptualize and analyze biogeographical distributions in relation to spatial environmental patterns. Both Joseph Grinnell and Charles Elton had attributed niches to environments. Attributing niches, instead, to species, allowed Hutchinson's key innovation: the formal severing of physical place from environment that is expressed by the duality. In biogeography, the physical world (a spatial extension of what Hutchinson called the biotope) is conceived as a map, each point (or cell) of which is characterized by its geographical coordinates and the local values of n environmental attributes at a given time. Exactly the same n environmental attributes define the corresponding niche space, as niche axes, allowing reciprocal projections between the geographic distribution of a species, actual or potential, past or future, and its niche. In biogeographical terms, the realized niche has come to express not only the effects of species interactions (as Hutchinson intended), but also constraints of dispersal limitation and the lack of contemporary environments corresponding to parts of the fundamental niche. Hutchinson's duality has been used to classify and map environments; model potential species distributions under past, present, and future climates; study the distributions of invasive species; discover new species; and simulate increasingly more realistic worlds, leading to spatially explicit, stochastic models that encompass speciation, extinction, range expansion, and evolutionary adaptation to changing environments. PMID:19805163

  13. HETEROTOPICALLY TRANSPLANTED CVO NEURAL STEM CELLS GENERATE NEURONS AND MIGRATE WITH SVZ CELLS IN THE ADULT MOUSE BRAIN

    PubMed Central

    Bennett, Lori B.; Cai, Jingli; Enikolopov, Grigori; Iacovitti, Lorraine

    2010-01-01

    Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ [3]. The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the Nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU+ cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. PMID:20298755

  14. The role of botulinum toxin A in treating neurogenic bladder

    PubMed Central

    Weckx, Filip; Tutolo, Manuela; De Ridder, Dirk

    2016-01-01

    Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox®, Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport®, Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future. PMID:26904413

  15. Preventing Kidney Injury in Children with Neurogenic Bladder Dysfunction

    PubMed Central

    Larijani, Faezeh Javadi; Moghtaderi, Mastaneh; Hajizadeh, Nilofar; Assadi, Farahnak

    2013-01-01

    The most common cause of neurogenic bladder dysfunction (NBD) in newborn infants is myelomeningocele. The pathophysiology almost always involves the bladder detrusor sphincter dyssynergy (DSD), which if untreated can cause severe and irreversible damage to the upper and lower urinary tracts. Early diagnosis and adequate management of NBD is critical to prevent both renal damage and bladder dysfunction and to reduce chances for the future surgeries. Initial investigation of the affected newborn infant includes a renal and bladder ultrasound, measurement of urine residual, determination of serum creatinine level, and urodynamics study. Voiding cystogram is indicated when either hydronephrosis or DSD is present. The main goal of treatment is prevention of urinary tract deterioration and achievement of continuance at an appropriate age. Clean intermittent catheterization (CIC) in combination with anticholinergic (oxybutynin) and antibiotics are instituted in those with high filling and voiding pressures, DSD and/or high grade reflux immediately after the myelomeningocele is repaired. Botulium toxin-A injection into detrusor is a safe alternative in patients with insufficient response or significant side effects to anticholinergic (oral or intravesical instillation) therapy. Surgery is an effective alternative in patients with persistent detrusor hyperactivity and/or dyssynergic detrusor sphincter despites of the CIC and maximum dosage of anticholinergic therapy. Children with NBD require care from a multidisciplinary team approach consisting of pediatricians, neurosurgeon, urologist, nephrologists, orthopedic surgeon, and other allied medical specialists. PMID:24498490

  16. Neurogenic regulation of proximal bicarbonate and chloride reabsorption.

    PubMed

    Cogan, M G

    1986-01-01

    Although a change in renal nerve activity is known to alter proximal reabsorption, it is unclear whether reabsorption of NaHCO3 or NaCl or both are affected. Sprague-Dawley rats (n = 10) were studied using free-flow micropuncture techniques during euvolemia and following acute ipsilateral denervation. Glomerular filtration rate and single nephron glomerular filtration rate were stable. Absolute proximal bicarbonate reabsorption fell following denervation (933 +/- 40 to 817 +/- 30 pmol/min) with a parallel reduction in chloride reabsorption (1,643 +/- 116 to 1,341 +/- 129 peq/min). Urinary sodium, potassium, bicarbonate, and chloride excretion all increased significantly. To further assess the physiological significance of neurogenic modulation of proximal transport, other rats (n = 6) were subjected to acute unilateral nephrectomy (AUN). There is evidence that AUN induces a contralateral natriuresis (renorenal reflex) at least partially by causing inhibition of efferent renal nerve traffic. AUN caused significant changes in proximal NaHCO3 and NaCl reabsorption as well as in whole kidney electrolyte excretion in the same pattern as had denervation. Prior denervation of the remaining kidney prevented the proximal and whole kidney response to AUN (n = 6). In conclusion, depression of renal nerve activity inhibits both NaHCO3 and NaCl reabsorption in the rat superficial proximal convoluted tubule. The data are consistent with the hypothesis that changes in renal nerve activity modify whole kidney electrolyte excretion under physiological conditions at least partially by regulating proximal transport.

  17. Making sense of hematopoietic stem cell niches

    PubMed Central

    Boulais, Philip E.

    2015-01-01

    The hematopoietic stem cell (HSC) niche commonly refers to the pairing of hematopoietic and mesenchymal cell populations that regulate HSC self-renewal, differentiation, and proliferation. Anatomic localization of the niche is a dynamic unit from the developmental stage that allows proliferating HSCs to expand before they reach the bone marrow where they adopt a quiescent phenotype that protects their integrity and functions. Recent studies have sought to clarify the complexity behind the HSC niche by assessing the contributions of specific cell populations to HSC maintenance. In particular, perivascular microenvironments in the bone marrow confer distinct vascular niches that regulate HSC quiescence and the supply of lineage-committed progenitors. Here, we review recent data on the cellular constituents and molecular mechanisms involved in the communication between HSCs and putative niches. PMID:25762174

  18. Out of Eden: Stem Cells and Their Niches

    NASA Astrophysics Data System (ADS)

    Watt, Fiona M.; Hogan, Brigid L. M.

    2000-02-01

    Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. Both intrinsic and extrinsic signals regulate stem cell fate and some of these signals have now been identified. Certain aspects of the stem cell microenvironment, or niche, are conserved between tissues, and this can be exploited in the application of stem cells to tissue replacement therapy.

  19. Transforming Growth Factor-Beta Signaling in the Neural Stem Cell Niche: A Therapeutic Target for Huntington's Disease

    PubMed Central

    Kandasamy, Mahesh; Reilmann, Ralf; Winkler, Jürgen; Bogdahn, Ulrich; Aigner, Ludwig

    2011-01-01

    The neural stem cell niches possess the regenerative capacity to generate new functional neurons in the adult brain, suggesting the possibility of endogenous neuronal replacement after injury or disease. Huntington disease (HD) is a neurodegenerative disease and characterized by neuronal loss in the basal ganglia, leading to motor, cognitive, and psychological disabilities. Apparently, in order to make use of the neural stem cell niche as a therapeutic concept for repair strategies in HD, it is important to understand the cellular and molecular composition of the neural stem cell niche under such neurodegenerative conditions. This paper mainly discusses the current knowledge on the regulation of the hippocampal neural stem cell niche in the adult brain and by which mechanism it might be compromised in the case of HD. PMID:21766020

  20. Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease

    PubMed Central

    Awad, Richard A

    2011-01-01

    Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel

  1. Early-life sexual segregation: ontogeny of isotopic niche differentiation in the Antarctic fur seal

    PubMed Central

    Kernaléguen, L.; Arnould, J. P. Y.; Guinet, C.; Cazelles, B.; Richard, P.; Cherel, Y.

    2016-01-01

    Investigating the ontogeny of niche differentiation enables to determine at which life-stages sexual segregation arises, providing insights into the main factors driving resource partitioning. We investigated the ontogeny of foraging ecology in Antarctic fur seals (Arctocephalus gazella), a highly dimorphic species with contrasting breeding strategies between sexes. Sequential δ13C and δ15N values of whiskers provided a longitudinal proxy of the foraging niche throughout the whole life of seals, from weaning, when size dimorphism is minimal to the age of 5. Females exhibited an early-life ontogenetic shift, from a total segregation during their first year at-sea, to a similar isotopic niche as breeding females as early as age 2. In contrast, males showed a progressive change in isotopic niche throughout their development such that 5-year-old males did not share the same niche as territorial bulls. Interestingly, males and females segregated straight after weaning with males appearing to feed in more southerly habitats than females. This spatial segregation was of similar amplitude as observed in breeding adults and was maintained throughout development. Such early-life niche differentiation is an unusual pattern and indicates size dimorphism and breeding constraints do not directly drive sexual segregation contrary to what has been assumed in otariid seals. PMID:27620663

  2. Early-life sexual segregation: ontogeny of isotopic niche differentiation in the Antarctic fur seal.

    PubMed

    Kernaléguen, L; Arnould, J P Y; Guinet, C; Cazelles, B; Richard, P; Cherel, Y

    2016-01-01

    Investigating the ontogeny of niche differentiation enables to determine at which life-stages sexual segregation arises, providing insights into the main factors driving resource partitioning. We investigated the ontogeny of foraging ecology in Antarctic fur seals (Arctocephalus gazella), a highly dimorphic species with contrasting breeding strategies between sexes. Sequential δ(13)C and δ(15)N values of whiskers provided a longitudinal proxy of the foraging niche throughout the whole life of seals, from weaning, when size dimorphism is minimal to the age of 5. Females exhibited an early-life ontogenetic shift, from a total segregation during their first year at-sea, to a similar isotopic niche as breeding females as early as age 2. In contrast, males showed a progressive change in isotopic niche throughout their development such that 5-year-old males did not share the same niche as territorial bulls. Interestingly, males and females segregated straight after weaning with males appearing to feed in more southerly habitats than females. This spatial segregation was of similar amplitude as observed in breeding adults and was maintained throughout development. Such early-life niche differentiation is an unusual pattern and indicates size dimorphism and breeding constraints do not directly drive sexual segregation contrary to what has been assumed in otariid seals. PMID:27620663

  3. Early-life sexual segregation: ontogeny of isotopic niche differentiation in the Antarctic fur seal.

    PubMed

    Kernaléguen, L; Arnould, J P Y; Guinet, C; Cazelles, B; Richard, P; Cherel, Y

    2016-09-13

    Investigating the ontogeny of niche differentiation enables to determine at which life-stages sexual segregation arises, providing insights into the main factors driving resource partitioning. We investigated the ontogeny of foraging ecology in Antarctic fur seals (Arctocephalus gazella), a highly dimorphic species with contrasting breeding strategies between sexes. Sequential δ(13)C and δ(15)N values of whiskers provided a longitudinal proxy of the foraging niche throughout the whole life of seals, from weaning, when size dimorphism is minimal to the age of 5. Females exhibited an early-life ontogenetic shift, from a total segregation during their first year at-sea, to a similar isotopic niche as breeding females as early as age 2. In contrast, males showed a progressive change in isotopic niche throughout their development such that 5-year-old males did not share the same niche as territorial bulls. Interestingly, males and females segregated straight after weaning with males appearing to feed in more southerly habitats than females. This spatial segregation was of similar amplitude as observed in breeding adults and was maintained throughout development. Such early-life niche differentiation is an unusual pattern and indicates size dimorphism and breeding constraints do not directly drive sexual segregation contrary to what has been assumed in otariid seals.

  4. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  5. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  6. Neurotoxic effects of AZT on developing and adult neurogenesis

    PubMed Central

    Demir, Meryem; Laywell, Eric D.

    2015-01-01

    Azidothymidine (AZT) is a synthetic, chain-terminating nucleoside analog used to treat HIV-1 infection. While AZT is not actively transported across the blood brain barrier, it does accumulate at high levels in cerebrospinal fluid, and subsequently diffuses into the overlying parenchyma. Due to the close anatomical proximity of the neurogenic niches to the ventricular system, we hypothesize that diffusion from CSF exposes neural stem/progenitor cells and their progeny to biologically relevant levels of AZT sufficient to perturb normal cell functions. We employed in vitro and in vivo models of mouse neurogenesis in order to assess the effects of AZT on developing and adult neurogenesis. Using in vitro assays we show that AZT reduces the population expansion potential of neural stem/progenitor cells by inducing senescence. Additionally, in a model of in vitro neurogenesis AZT severely attenuates neuroblast production. These effects are mirrored in vivo by clinically-relevant animal models. We show that in utero AZT exposure perturbs both population expansion and neurogenesis among neural stem/progenitor cells. Additionally, a short-term AZT regimen in adult mice suppresses subependymal zone neurogenesis. These data reveal novel negative effects of AZT on neural stem cell biology. Given that the sequelae of HIV infection often include neurologic deficits—subsumed under AIDS Dementia Complex (Brew, 1999)—it is important to determine to what extent AZT negatively affects neurological function in ways that contribute to, or exacerbate, ADC in order to avoid attributing iatrogenic drug effects to the underlying disease process, and thereby skewing the risk/benefit analysis of AZT therapy. PMID:25852464

  7. Neurotoxic effects of AZT on developing and adult neurogenesis.

    PubMed

    Demir, Meryem; Laywell, Eric D

    2015-01-01

    Azidothymidine (AZT) is a synthetic, chain-terminating nucleoside analog used to treat HIV-1 infection. While AZT is not actively transported across the blood brain barrier, it does accumulate at high levels in cerebrospinal fluid, and subsequently diffuses into the overlying parenchyma. Due to the close anatomical proximity of the neurogenic niches to the ventricular system, we hypothesize that diffusion from CSF exposes neural stem/progenitor cells and their progeny to biologically relevant levels of AZT sufficient to perturb normal cell functions. We employed in vitro and in vivo models of mouse neurogenesis in order to assess the effects of AZT on developing and adult neurogenesis. Using in vitro assays we show that AZT reduces the population expansion potential of neural stem/progenitor cells by inducing senescence. Additionally, in a model of in vitro neurogenesis AZT severely attenuates neuroblast production. These effects are mirrored in vivo by clinically-relevant animal models. We show that in utero AZT exposure perturbs both population expansion and neurogenesis among neural stem/progenitor cells. Additionally, a short-term AZT regimen in adult mice suppresses subependymal zone neurogenesis. These data reveal novel negative effects of AZT on neural stem cell biology. Given that the sequelae of HIV infection often include neurologic deficits-subsumed under AIDS Dementia Complex (Brew, 1999)-it is important to determine to what extent AZT negatively affects neurological function in ways that contribute to, or exacerbate, ADC in order to avoid attributing iatrogenic drug effects to the underlying disease process, and thereby skewing the risk/benefit analysis of AZT therapy. PMID:25852464

  8. Striatal astrocytes produce neuroblasts in an excitotoxic model of Huntington's disease.

    PubMed

    Nato, Giulia; Caramello, Alessia; Trova, Sara; Avataneo, Valeria; Rolando, Chiara; Taylor, Verdon; Buffo, Annalisa; Peretto, Paolo; Luzzati, Federico

    2015-03-01

    In the adult brain, subsets of astrocytic cells residing in well-defined neurogenic niches constitutively generate neurons throughout life. Brain lesions can stimulate neurogenesis in otherwise non-neurogenic regions, but whether local astrocytic cells generate neurons in these conditions is unresolved. Here, through genetic and viral lineage tracing in mice, we demonstrate that striatal astrocytes become neurogenic following an acute excitotoxic lesion. Similar to astrocytes of adult germinal niches, these activated parenchymal progenitors express nestin and generate neurons through the formation of transit amplifying progenitors. These results shed new light on the neurogenic potential of the adult brain parenchyma. PMID:25655705

  9. Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis

    PubMed Central

    Garthe, Alexander; Roeder, Ingo

    2016-01-01

    ABSTRACT We here show that living in a stimulus‐rich environment (ENR) improves water maze learning with respect to specific key indicators that in previous loss‐of‐function experiments have been shown to rely on adult hippocampal neurogenesis. Analyzing the strategies employed by mice to locate the hidden platform in the water maze revealed that ENR facilitated task acquisition by increasing the probability to use effective search strategies. ENR also enhanced the animals’ behavioral flexibility, when the escape platform was moved to a new location. Treatment with temozolomide, which is known to reduce adult neurogenesis, abolished the effects of ENR on both acquisition and flexibility, while leaving other aspects of water maze learning untouched. These characteristic effects and interdependencies were not seen in parallel experiments with voluntary wheel running (RUN), a second pro‐neurogenic behavioral stimulus. Since the histological assessment of adult neurogenesis is by necessity an end‐point measure, the levels of neurogenesis over the course of the experiment can only be inferred and the present study focused on behavioral parameters as analytical endpoints. Although the correlation of physical activity with precursor cell proliferation and of learning and the survival of new neurons is well established, how the specific functional effects described here relate to dynamic changes in the stem cell niche remains to be addressed. Nevertheless, our findings support the hypothesis that adult neurogenesis is a critical mechanism underlying the beneficial effects of leading an active live, rich in experiences. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:26311488

  10. THE NICHE CONSTRUCTION PERSPECTIVE: A CRITICAL APPRAISAL*

    PubMed Central

    Scott-Phillips, Thomas C; Laland, Kevin N; Shuker, David M; Dickins, Thomas E; West, Stuart A

    2014-01-01

    Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process). PMID:24325256

  11. Niche construction game cancer cells play

    NASA Astrophysics Data System (ADS)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  12. Hutchinson's duality: The once and future niche

    PubMed Central

    Colwell, Robert K.; Rangel, Thiago F.

    2009-01-01

    The duality between “niche” and “biotope” proposed by G. Evelyn Hutchinson provides a powerful way to conceptualize and analyze biogeographical distributions in relation to spatial environmental patterns. Both Joseph Grinnell and Charles Elton had attributed niches to environments. Attributing niches, instead, to species, allowed Hutchinson's key innovation: the formal severing of physical place from environment that is expressed by the duality. In biogeography, the physical world (a spatial extension of what Hutchinson called the biotope) is conceived as a map, each point (or cell) of which is characterized by its geographical coordinates and the local values of n environmental attributes at a given time. Exactly the same n environmental attributes define the corresponding niche space, as niche axes, allowing reciprocal projections between the geographic distribution of a species, actual or potential, past or future, and its niche. In biogeographical terms, the realized niche has come to express not only the effects of species interactions (as Hutchinson intended), but also constraints of dispersal limitation and the lack of contemporary environments corresponding to parts of the fundamental niche. Hutchinson's duality has been used to classify and map environments; model potential species distributions under past, present, and future climates; study the distributions of invasive species; discover new species; and simulate increasingly more realistic worlds, leading to spatially explicit, stochastic models that encompass speciation, extinction, range expansion, and evolutionary adaptation to changing environments. PMID:19805163

  13. Cultural niche construction in a metapopulation.

    PubMed

    Borenstein, Elhanan; Kendal, Jeremy; Feldman, Marcus

    2006-08-01

    Cultural niche construction is the process by which certain evolving cultural traits form a cultural niche that affects the evolution of other genetic and cultural traits [Laland, K., et al., 2001. Cultural niche construction and human evolution. J. Evol. Biol. 14, 22-33; Ihara, Y., Feldman, M., 2004. Cultural niche construction and the evolution of small family size. Theor. Popul. Biol. 65, 105-111]. In this study we focus on cultural niche construction in a metapopulation (a population of populations), where the frequency of one cultural trait (e.g. the level of education) determines the transmission rate of a second trait (e.g. the adoption of fertility reduction preferences) within and between populations. We formulate the Metapopulation Cultural Niche Construction (MPCNC) model by defining the cultural niche induced by the first trait as the construction of a social interaction network on which the second trait may percolate. Analysis of the model reveals dynamics that are markedly different from those observed in a single population, allowing, for example, different (or even opposing) dynamics in each population. In particular, this model can account for the puzzling phenomenon reported in previous studies [Bongaarts, J., Watkins, S., 1996. Social interactions and contemporary fertility transitions. Popul. Dev. Rev. 22 (4), 639-682] that the onset of the demographic transition in different countries occurred at ever lower levels of development.

  14. Rethinking adaptation: the niche-construction perspective.

    PubMed

    Day, Rachel L; Laland, Kevin N; Odling-Smee, F John

    2003-01-01

    Niche construction refers to the capacity of organisms to construct, modify, and select important components of their local environments, such as nests, burrows, pupal cases, chemicals, and nutrients. A small but increasing number of evolutionary biologists regard niche construction as an evolutionary process in its own right, rather than as a mere product of natural selection. Through niche construction organisms not only influence the nature of their world, but also in part determine the selection pressures to which they and their descendants are exposed, and they do so in a non-random manner. Mathematical population genetics analyses have revealed that niche construction is likely to be evolutionarily consequential because of the feedback that it generates in the evolutionary process. A parallel movement has emerged in ecosystem ecology, where researchers stress the utility of regarding organisms as ecosystem engineers, who partly control energy and matter flows. From the niche construction standpoint, the evolving complementary match between organisms and environments is the product of reciprocal interacting processes of natural selection and niche construction. This essay reviews the arguments put forward in favor of the niche-construction perspective.

  15. The niche construction perspective: a critical appraisal.

    PubMed

    Scott-Phillips, Thomas C; Laland, Kevin N; Shuker, David M; Dickins, Thomas E; West, Stuart A

    2014-05-01

    Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process).

  16. Niche construction game cancer cells play*

    PubMed Central

    Bergman, Aviv; Gligorijevic, Bojana

    2016-01-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology. PMID:27656339

  17. The niche construction perspective: a critical appraisal.

    PubMed

    Scott-Phillips, Thomas C; Laland, Kevin N; Shuker, David M; Dickins, Thomas E; West, Stuart A

    2014-05-01

    Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process). PMID:24325256

  18. Sensory and other neurogenic effects of exposures to airborne office dust

    NASA Astrophysics Data System (ADS)

    Mølhave, L.; Kjærgaard, S. K.; Attermann, J.

    This Danish Office Dust Experiment investigated the response of 24 healthy non-sensitive adult subjects to exposure to normal office dust in the air (7 μg m -3 clean air, 136 and 390 μg m -3 TSP). The dust had no major identifiable specific reactive components. The exposure duration was 5 1/4 h and was arranged in a climate chamber in controlled atmospheric conditions. Measurements were made acutely at exposure onset, subacutely at exposure end and next day (late). As secondary aims the time course and threshold of any observed effect of the exposures, and the characteristics of any hyperresponding subgroup were investigated. In a questionnaire with 36 questions the dust exposures caused increased acute, subacute and late perceptions of reduced air quality, acute and subacute increased odor intensity, acute eye irritation, acute and late heavy head, subacute feeling of perspiration, and subacute general irritation. Cough increased subacutely during exposures. In addition, a performance test showed effects of dust exposures which also affected "Mood Scale" ratings. No effect was seen on an addition test for distraction, and objective measurements of skin humidity. The overall conclusion of the study is that healthy subjects without hypersensitivity reactions seem to respond to airborne house dust. The responses are both subjective sensory reactions and other neurogenic effects even at exposure levels within the range found in normal buildings. Some of the effects appeared acutely and decreased through adaptation while others increased during prolonged exposure and remained for more than 17 h after the exposure ended. The findings may indicate for this type of dust a threshold level for the dose-response relationships below 140 μg m -3.

  19. Why do niches develop in Caesarean uterine scars? Hypotheses on the aetiology of niche development.

    PubMed

    Vervoort, A J M W; Uittenbogaard, L B; Hehenkamp, W J K; Brölmann, H A M; Mol, B W J; Huirne, J A F

    2015-12-01

    Caesarean section (CS) results in the occurrence of the phenomenon 'niche'. A 'niche' describes the presence of a hypoechoic area within the myometrium of the lower uterine segment, reflecting a discontinuation of the myometrium at the site of a previous CS. Using gel or saline instillation sonohysterography, a niche is identified in the scar in more than half of the women who had had a CS, most with the uterus closed in one single layer, without closure of the peritoneum. An incompletely healed scar is a long-term complication of the CS and is associated with more gynaecological symptoms than is commonly acknowledged. Approximately 30% of women with a niche report spotting at 6-12 months after their CS. Other reported symptoms in women with a niche are dysmenorrhoea, chronic pelvic pain and dyspareunia. Given the association between a niche and gynaecological symptoms, obstetric complications and potentially with subfertility, it is important to elucidate the aetiology of niche development after CS in order to develop preventive strategies. Based on current published data and our observations during sonographic, hysteroscopic and laparoscopic evaluations of niches we postulate some hypotheses on niche development. Possible factors that could play a role in niche development include a very low incision through cervical tissue, inadequate suturing technique during closure of the uterine scar, surgical interventions that increase adhesion formation or patient-related factors that impair wound healing or increase inflammation or adhesion formation.

  20. Experience with botulinum toxin type A in the treatment of neurogenic detrusor overactivity in clinical practice

    PubMed Central

    Juenemann, Klaus-Peter

    2014-01-01

    Control of the lower urinary tract is a complex, multilevel process that involves both the peripheral and central nervous system. Neurogenic lower urinary tract dysfunction (LUTD) is a widespread chronic illness that impairs millions of people worldwide. Neurogenic LUTD has a major impact on quality of life, affecting emotional, social, sexual, occupational and physical aspects of daily life, and in addition to the debilitating manifestations for patients, it also imposes a substantial economic burden on every healthcare system. First-line treatment for neurogenic LUTD includes antimuscarinics and some form of catheterization, preferably intermittent self-catheterization. However, the treatment effect is often unsatisfactory, so that other options have to be considered. Moreover, neurogenic LUTD is a challenge because all available treatment modalities (i.e. conservative, minimally invasive and invasive therapies) may fail. In recent years, botulinum neurotoxin type A (BoNT/A) treatment has been shown to be an effective pharmacological therapy option in patients refractory to antimuscarinic and neurogenic detrusor overactivity (NDO). Several studies have shown that BoNT/A injection significantly reduces detrusor muscle overactivity. Also BoNT/A treatment of NDO has revealed a significant improvement of lower urinary tract function with regard to reduced urinary incontinence, reduced detrusor pressure, increased bladder capacity and improved quality of life in NDO. PMID:24489607

  1. The reliability of differentiating neurogenic claudication from vascular claudication based on symptomatic presentation

    PubMed Central

    Nadeau, Mélissa; Rosas-Arellano, M. Patricia; Gurr, Kevin R.; Bailey, Stewart I.; Taylor, David C.; Grewal, Ruby; Lawlor, D. Kirk; Bailey, Chris S.

    2013-01-01

    Background Intermittent claudication can be neurogenic or vascular. Physicians use a profile based on symptom attributes to differentiate the 2 types of claudication, and this guides their investigations for diagnosis of the underlying pathology. We evaluated the validity of these symptom attributes in differentiating neurogenic from vascular claudication. Methods Patients with a diagnosis of lumbar spinal stenosis (LSS) or peripheral vascular disease (PVD) who reported claudication answered 14 questions characterizing their symptoms. We determined the sensitivity, specificity and positive and negative likelihood ratios (PLR and NLR) for neurogenic and vascular claudication for each symptom attribute. Results We studied 53 patients. The most sensitive symptom attribute to rule out LSS was the absence of “triggering of pain with standing alone” (sensitivity 0.97, NLR 0.050). Pain alleviators and symptom location data showed a weak clinical significance for LSS and PVD. Constellation of symptoms yielded the strongest associations: patients with a positive shopping cart sign whose symptoms were located above the knees, triggered with standing alone and relieved with sitting had a strong likelihood of neurogenic claudication (PLR 13). Patients with symptoms in the calf that were relieved with standing alone had a strong likelihood of vascular claudication (PLR 20.0). Conclusion The classic symptom attributes used to differentiate neurogenic from vascular claudication are at best weakly valid independently. However, certain constellation of symptoms are much more indicative of etiology. These results can guide general practitioners in their evaluation of and investigation for claudication. PMID:24284143

  2. The probabilistic niche model reveals substantial variation in the niche structure of empirical food webs.

    PubMed

    Williams, Richard J; Purves, Drew W

    2011-09-01

    The structure of food webs, complex networks of interspecies feeding interactions, plays a crucial role in ecosystem resilience and function, and understanding food web structure remains a central problem in ecology. Previous studies have shown that key features of empirical food webs can be reproduced by low-dimensional "niche" models. Here we examine the form and variability of food web niche structure by fitting a probabilistic niche model to 37 empirical food webs, a much larger number of food webs than used in previous studies. The model relaxes previous assumptions about parameter distributions and hierarchy and returns parameter estimates for each species in each web. The model significantly outperforms previous niche model variants and also performs well for several webs where a body-size-based niche model performs poorly, implying that traits other than body size are important in structuring these webs' niche space. Parameter estimates frequently violate previous models' assumptions: in 19 of 37 webs, parameter values are not significantly hierarchical, 32 of 37 webs have nonuniform niche value distributions, and 15 of 37 webs lack a correlation between niche width and niche position. Extending the model to a two-dimensional niche space yields networks with a mixture of one- and two-dimensional niches and provides a significantly better fit for webs with a large number of species and links. These results confirm that food webs are strongly niche-structured but reveal substantial variation in the form of the niche structuring, a result with fundamental implications for ecosystem resilience and function.

  3. [Relation between fundamental and realized ecological niche].

    PubMed

    Severtsov, A S

    2012-01-01

    Since species are formed in course of evolutionary process, their ecological niches are formed in the evolutionary process, too. Species exist in a state of evolutionary stasis diring hundreds of thousands and millions years. Stasis in sustained mainly by counterbalance of vectors of directional selection. Niche can be viewed as a multidimensional structure. Multitude of environmental factors acts upon every population, which cause elimination and, by that, selection for adaptation to each eliminating factor. Different directions of these vectors of selection lead to their counteractions; selection in one direction is interfered by selection in an opposite direction. The counterbalance of vectors of selection interferes with progressive evolution thus supporting stasis. During species existence in a stasis condition it endures a whole set of various deterioration of environment. Such deteriorations lead to imbalance of selective processes. Unbalanced vectors of selection form adaptations to extreme conditions of existence. Such adaptations are superfluous as for usual conditions; but they define fitness borders and, by that, borders of a fundamental niche. Realized niche, as well as fundamental one, is a multidimensional structure. Each population occupies a subniche of the specific realized niche. Thus, it occupies habitats where conditions are as close to an ecological optimum as can be admitted by the conditions in the given part of the areal. The sum of all subniches of populations--the specific realized niche--coincides with a part of fundamental niche because only the part of adaptive possibilities of a species sufficient for existence in the given environment is used. Interspecific competition, even when it is capable to restrict consumption of limiting resources, is not the reason of the realized niche limitation. Restriction of one or two of niche parameters does not influece all others parameters of its multidimensional space.

  4. Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone.

    PubMed

    Campos-Ordoñez, Tania; Herranz-Pérez, Vicente; Chaichana, Kaisorn L; Rincon-Torroella, Jordina; Rigamonti, Daniele; García-Verdugo, Jose M; Quiñones-Hinojosa, Alfredo; Gonzalez-Perez, Oscar

    2014-11-01

    Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n=18 per group), the degree of ventricular dilatation and cellular composition of the subventricular zone were studied by immunofluorescence and transmission electron microscopy. In adult patients (age>18years), the sizes of the subventricular zone, corpus callosum, and internal capsule were analyzed by magnetic resonance images obtained from patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day hydrocephalus had a reduced number of Ki67+ and doublecortin+cells on immunofluorescence, as well as decreased number of neural progenitors and neuroblasts in the subventricular zone on electron microscopy analysis as compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix structures (fractones) contacting the ventricular lumen and blood vessels were also observed around the subventricular zone in mice with hydrocephalus. In humans, the widths of the subventricular zone, corpus callosum, and internal capsule in patients with aqueductal stenosis were significantly smaller than age and gender-matched patients without aqueductal stenosis. In summary, supratentorial hydrocephalus reduces the proliferation rate of neural progenitors and modifies the cytoarchitecture and extracellular matrix compounds of the subventricular zone. In humans, this similar process reduces the subventricular

  5. Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone.

    PubMed

    Campos-Ordoñez, Tania; Herranz-Pérez, Vicente; Chaichana, Kaisorn L; Rincon-Torroella, Jordina; Rigamonti, Daniele; García-Verdugo, Jose M; Quiñones-Hinojosa, Alfredo; Gonzalez-Perez, Oscar

    2014-11-01

    Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n=18 per group), the degree of ventricular dilatation and cellular composition of the subventricular zone were studied by immunofluorescence and transmission electron microscopy. In adult patients (age>18years), the sizes of the subventricular zone, corpus callosum, and internal capsule were analyzed by magnetic resonance images obtained from patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day hydrocephalus had a reduced number of Ki67+ and doublecortin+cells on immunofluorescence, as well as decreased number of neural progenitors and neuroblasts in the subventricular zone on electron microscopy analysis as compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix structures (fractones) contacting the ventricular lumen and blood vessels were also observed around the subventricular zone in mice with hydrocephalus. In humans, the widths of the subventricular zone, corpus callosum, and internal capsule in patients with aqueductal stenosis were significantly smaller than age and gender-matched patients without aqueductal stenosis. In summary, supratentorial hydrocephalus reduces the proliferation rate of neural progenitors and modifies the cytoarchitecture and extracellular matrix compounds of the subventricular zone. In humans, this similar process reduces the subventricular

  6. Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone

    PubMed Central

    Campos-Ordoñez, Tania; Herranz-Pérez, Vicente; Chaichana, Kaisorn L.; Rincon-Torroella, Jordina; Rigamonti, Daniele; García-Verdugo, Jose M.; Quiñones-Hinojosa, Alfredo; Gonzalez-Perez, Oscar

    2014-01-01

    Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n = 18 per group), the degree of ventricular dilatation and cellular composition of the subventricular zone were studied by immunofluorescence and transmission electron microscopy. In adult patients (age > 18 years), the sizes of the subventricular zone, corpus callosum, and internal capsule were analyzed by magnetic resonance images obtained from patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day hydrocephalus had a reduced number of Ki67+ and doublecortin+ cells on immunofluorescence, as well as decreased number of neural progenitors and neuroblasts in the subventricular zone on electron microscopy analysis as compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix structures (fractones) contacting the ventricular lumen and blood vessels were also observed around the subventricular zone in mice with hydrocephalus. In humans, the widths of the subventricular zone, corpus callosum, and internal capsule in patients with aqueductal stenosis were significantly smaller than age and gender-matched patients without aqueductal stenosis. In summary, supratentorial hydrocephalus reduces the proliferation rate of neural progenitors and modifies the cytoarchitecture and extracellular matrix compounds of the subventricular zone. In humans, this similar process reduces the

  7. The United States pork niche market phenomenon.

    PubMed

    Honeyman, M S; Pirog, R S; Huber, G H; Lammers, P J; Hermann, J R

    2006-08-01

    After the broad industrialization of the US pork industry, there has been a development of niche markets for export and domestic pork; that is, there is a pork niche market phenomenon. The US pork niche market phenomenon is characterized, and 2 of the major markets are explained in detail. With the Midwest's tradition of a diversified family-based agriculture and record low hog prices of the late 1990s, the conditions were conducive for this phenomenon to develop. Pork niche markets utilize various sales methods including Internet sales, local abattoir sales, direct marketing, farmer networks, and targeting to organized groups. In 2003, there were approximately 35 to 40 active pork niche marketing efforts in Iowa. The Berkshire breed is an example of a swine breed that has had a recent resurgence because of niche markets. Berkshire pork is known for tenderness and excellent quality. Berkshire registrations have increased 4-fold in the last 10 yr. One of the larger niche marketers of "natural pork" is Niman Ranch Pork, which has more than 400 farmer-producers and processes about 2,500 pigs weekly. Many US consumers of pork are interested in issues concerning the environment, food safety, pig welfare, and pig farm ownership and structure. These consumers may be willing to pay more for pork from farmers who are also concerned about these issues. Small- and medium-sized swine farmers are active in pork niche markets. Niche markets claim product differentiation by superior or unique product quality and social attributes. Quality attributes include certain swine breeds, and meat quality, freshness, taste or flavor, and tenderness. Social or credence attributes often are claimed and include freedom from antibiotics and growth promotants; local family farm production; natural, organic, outdoor, or bedded rearing; humane rearing; known origin; environmentally friendly production; and the absence of animal by-products in the feed. Niche pork markets and alternative swine

  8. The United States pork niche market phenomenon.

    PubMed

    Honeyman, M S; Pirog, R S; Huber, G H; Lammers, P J; Hermann, J R

    2006-08-01

    After the broad industrialization of the US pork industry, there has been a development of niche markets for export and domestic pork; that is, there is a pork niche market phenomenon. The US pork niche market phenomenon is characterized, and 2 of the major markets are explained in detail. With the Midwest's tradition of a diversified family-based agriculture and record low hog prices of the late 1990s, the conditions were conducive for this phenomenon to develop. Pork niche markets utilize various sales methods including Internet sales, local abattoir sales, direct marketing, farmer networks, and targeting to organized groups. In 2003, there were approximately 35 to 40 active pork niche marketing efforts in Iowa. The Berkshire breed is an example of a swine breed that has had a recent resurgence because of niche markets. Berkshire pork is known for tenderness and excellent quality. Berkshire registrations have increased 4-fold in the last 10 yr. One of the larger niche marketers of "natural pork" is Niman Ranch Pork, which has more than 400 farmer-producers and processes about 2,500 pigs weekly. Many US consumers of pork are interested in issues concerning the environment, food safety, pig welfare, and pig farm ownership and structure. These consumers may be willing to pay more for pork from farmers who are also concerned about these issues. Small- and medium-sized swine farmers are active in pork niche markets. Niche markets claim product differentiation by superior or unique product quality and social attributes. Quality attributes include certain swine breeds, and meat quality, freshness, taste or flavor, and tenderness. Social or credence attributes often are claimed and include freedom from antibiotics and growth promotants; local family farm production; natural, organic, outdoor, or bedded rearing; humane rearing; known origin; environmentally friendly production; and the absence of animal by-products in the feed. Niche pork markets and alternative swine

  9. The extraocular muscle stem cell niche is resistant to ageing and disease

    PubMed Central

    Formicola, Luigi; Marazzi, Giovanna; Sassoon, David A.

    2014-01-01

    Specific muscles are spared in many degenerative myopathies. Most notably, the extraocular muscles (EOMs) do not show clinical signs of late stage myopathies including the accumulation of fibrosis and fat. It has been proposed that an altered stem cell niche underlies the resistance of EOMs in these pathologies, however, to date, no reports have provided a detailed characterization of the EOM stem cell niche. PW1/Peg3 is expressed in progenitor cells in all adult tissues including satellite cells and a subset of interstitial non-satellite cell progenitors in muscle. These PW1-positive interstitial cells (PICs) include a fibroadipogenic progenitor population (FAP) that give rise to fat and fibrosis in late stage myopathies. PICs/FAPs are mobilized following injury and FAPs exert a promyogenic role upon myoblasts in vitro but require the presence of a minimal population of satellite cells in vivo. We and others recently described that FAPs express promyogenic factors while satellite cells express antimyogenic factors suggesting that PICs/FAPs act as support niche cells in skeletal muscle through paracrine interactions. We analyzed the EOM stem cell niche in young adult and aged wild-type mice and found that the balance between PICs and satellite cells within the EOM stem cell niche is maintained throughout life. Moreover, in the adult mdx mouse model for Duchenne muscular dystrophy (DMD), the EOM stem cell niche is unperturbed compared to normal mice, in contrast to Tibialis Anterior (TA) muscle, which displays signs of ongoing degeneration/regeneration. Regenerating mdx TA shows increased levels of both PICs and satellite cells, comparable to normal unaffected EOMs. We propose that the increase in PICs that we observe in normal EOMs contributes to preserving the integrity of the myofibers and satellite cells. Our data suggest that molecular cues regulating muscle regeneration are intrinsic properties of EOMs. PMID:25520657

  10. Congenital neurogenic muscular atrophy in megaconial myopathy due to a mutation in CHKB gene.

    PubMed

    Castro-Gago, Manuel; Dacruz-Alvarez, David; Pintos-Martínez, Elena; Beiras-Iglesias, Andrés; Arenas, Joaquín; Martín, Miguel Ángel; Martínez-Azorín, Francisco

    2016-01-01

    Choline kinase beta gene (CHKB) mutations have been identified in Megaconial Congenital Muscular Dystrophy (MDCMC) patients, a very rare inborn error of metabolism with 21 cases reported worldwide. We report the case of a Spanish boy of Caucasian origin who presented a generalized congenital muscular hypotonia, more intense at lower limb muscles, mildly elevated creatine kinase (CK), serum aspartate transaminase (AST) and lactate. Electromyography (EMG) showed neurogenic potentials in the proximal muscles. Histological studies of a muscle biopsy showed neurogenic atrophy with enlarged mitochondria in the periphery of the fibers, and complex I deficiency. Finally, genetic analysis showed the presence of a homozygous mutation in the gene for choline kinase beta (CHKB: NM_005198.4:c.810T>A, p.Tyr270(∗)). We describe here the second Spanish patient whit mutation in CHKB gene, who despite having the same mutation, presented an atypical aspect: congenital neurogenic muscular atrophy progressing to a combined neuropathic and myopathic phenotype (mixed pattern).

  11. Ventral midbrain neural stem cells have delayed neurogenic potential in vitro.

    PubMed

    Hegarty, Shane V; Spitere, Katie; Sullivan, Aideen M; O'Keeffe, Gerard W

    2014-01-24

    Neural stem cells (NSCs) have been the focus of an intensive effort to direct their differentiation in vitro towards desired neuronal phenotypes for cell replacement therapies. It is thought that NSCs derived from older embryos have limited neurogenic capacity and are restricted towards an astroglial fate. This idea is largely based on studies that typically analysed NSC-derived progeny following one week of in vitro differentiation. In this report, the neurogenic capacity of older ventral midbrain (VM) NSCs was assessed. When the older NSCs were differentiated for three weeks, there were significant increases in the numbers of newly born neurons at 14 and 21 days, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation. Therefore this study demonstrates that older NSCs retain significantly more neurogenic potential than was previously thought. These data have implications for NSC preparatory protocols and the choice of donor age for cell transplantation studies, and contributes to the understanding of NSC behaviour in vitro.

  12. Cellular complexity of the bone marrow hematopoietic stem cell niche.

    PubMed

    Calvi, Laura M; Link, Daniel C

    2014-01-01

    The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500 billion blood cells. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices which include quiescence, self-renewal, differentiation, and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of the microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche.

  13. Retinal pathways influence temporal niche

    PubMed Central

    Doyle, Susan E.; Yoshikawa, Tomoko; Hillson, Holly; Menaker, Michael

    2008-01-01

    In mammals, light input from the retina entrains central circadian oscillators located in the suprachiasmatic nuclei (SCN). The phase of circadian activity rhythms with respect to the external light:dark cycle is reversed in diurnal and nocturnal species, although the phase of SCN rhythms relative to the light cycle remains unchanged. Neural mechanisms downstream from the SCN are therefore believed to determine diurnality or nocturnality. Here, we report a switch from nocturnal to diurnal entrainment of circadian activity rhythms in double-knockout mice lacking the inner-retinal photopigment melanopsin (OPN4) and RPE65, a key protein used in retinal chromophore recycling. These mice retained only a small amount of rod function. The change in entrainment phase of Rpe65−/−;Opn4−/− mice was accompanied by a reversal of the rhythm of clock gene expression in the SCN and a reversal in acute masking effects of both light and darkness on activity, suggesting that the nocturnal to diurnal switch is due to a change in the neural response to light upstream from the SCN. A switch from nocturnal to diurnal activity rhythms was also found in wild-type mice transferred from standard intensity light:dark cycles to light:dark cycles in which the intensity of the light phase was reduced to scotopic levels. These results reveal a novel mechanism by which changes in retinal input can mediate acute temporal-niche switching. PMID:18695249

  14. Human niche construction in interdisciplinary focus

    PubMed Central

    Kendal, Jeremy; Tehrani, Jamshid J.; Odling-Smee, John

    2011-01-01

    Niche construction is an endogenous causal process in evolution, reciprocal to the causal process of natural selection. It works by adding ecological inheritance, comprising the inheritance of natural selection pressures previously modified by niche construction, to genetic inheritance in evolution. Human niche construction modifies selection pressures in environments in ways that affect both human evolution, and the evolution of other species. Human ecological inheritance is exceptionally potent because it includes the social transmission and inheritance of cultural knowledge, and material culture. Human genetic inheritance in combination with human cultural inheritance thus provides a basis for gene–culture coevolution, and multivariate dynamics in cultural evolution. Niche construction theory potentially integrates the biological and social aspects of the human sciences. We elaborate on these processes, and provide brief introductions to each of the papers published in this theme issue. PMID:21320894

  15. Stem cell niche engineering through droplet microfluidics.

    PubMed

    Allazetta, Simone; Lutolf, Matthias P

    2015-12-01

    Stem cells reside in complex niches in which their behaviour is tightly regulated by various biochemical and biophysical signals. In order to unveil some of the crucial stem cell-niche interactions and expedite the implementation of stem cells in clinical and pharmaceutical applications, in vitro methodologies are being developed to reconstruct key features of stem cell niches. Recently, droplet-based microfluidics has emerged as a promising strategy to build stem cell niche models in a miniaturized and highly precise fashion. This review highlights current advances in using droplet microfluidics in stem cell biology. We also discuss recent efforts in which microgel technology has been interfaced with high-throughput analyses to engender screening paradigms with an unparalleled potential for basic and applied biological studies.

  16. CROSS DRIFT ALCOVE/NICHE UTILITIES ANALYSIS

    SciTech Connect

    S. Goodin

    1999-07-08

    The purpose of this analysis is to provide the design basis and general arrangement requirements of the non-potable water, waste water, compressed air and ventilation (post excavation) utilities required in support of the Cross Drift alcoves and niches.

  17. Human niche construction in interdisciplinary focus.

    PubMed

    Kendal, Jeremy; Tehrani, Jamshid J; Odling-Smee, John

    2011-03-27

    Niche construction is an endogenous causal process in evolution, reciprocal to the causal process of natural selection. It works by adding ecological inheritance, comprising the inheritance of natural selection pressures previously modified by niche construction, to genetic inheritance in evolution. Human niche construction modifies selection pressures in environments in ways that affect both human evolution, and the evolution of other species. Human ecological inheritance is exceptionally potent because it includes the social transmission and inheritance of cultural knowledge, and material culture. Human genetic inheritance in combination with human cultural inheritance thus provides a basis for gene-culture coevolution, and multivariate dynamics in cultural evolution. Niche construction theory potentially integrates the biological and social aspects of the human sciences. We elaborate on these processes, and provide brief introductions to each of the papers published in this theme issue.

  18. Niche construction, genetic evolution and cultural change.

    PubMed

    Odling-Smee, F J

    1995-12-01

    In evolution, adaptation is traditionally viewed as a process by which natural selection moulds organisms to fit pre-established environmental templates. The changes organisms cause in environments are seldom thought evolutionarily significant. However, organisms partly create their own environments by 'niche construction'. A formal model of niche construction is discussed. It focusses on two genetic loci, E and A. It assumes: This model produces some surprising results. For example, timelags occur between the spread of niche construction and the response to the selection it generates. Niche construction also enhances the role of phenotypes in evolution. Organisms not only carry and propagate genes, but they also modify the selection pressures that select those genes. This dual role changes the relationship between genetic evolution; individual development; learning; and cultural processes in human beings.

  19. [Bone and Stem Cells. Immune cell regulation by the bone marrow niche].

    PubMed

    Terashima, Asuka; Takayanagi, Hiroshi

    2014-04-01

    Adult hematopoietic stem cells (HSCs) are maintained in the bone marrow and give rise to all blood cell types. The maintenance and the differentiation of blood cells including immune cells are essential for host defense and oxygen delivery. HSCs are maintained in microenvironments called stem cell niches, which consists of various cell types in bone marrow. Recently, new visualization technologies and assay systems brought advances in studies on the stem cell niche. In addition, several reports demonstrated that osteoblasts and osteocytes regulate not only HSC homeostasis but also immune cell differentiation, suggesting a close relationship between bone cells and HSCs.

  20. Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands.

    PubMed

    Hsu, Hwei-Jan; Drummond-Barbosa, Daniela

    2011-02-15

    Adult stem cells reside in specialized microenvironments, or niches, that are essential for their function in vivo. Stem cells are physically attached to the niche, which provides secreted factors that promote their self-renewal and proliferation. Despite intense research on the role of the niche in regulating stem cell function, much less is known about how the niche itself is controlled. We previously showed that insulin signals directly stimulate germline stem cell (GSC) division and indirectly promote GSC maintenance via the niche in Drosophila. Insulin-like peptides are required for maintenance of cap cells (a major component of the niche) via modulation of Notch signaling, and they also control attachment of GSCs to cap cells and E-cadherin levels at the cap cell-GSC junction. Here, we further dissect the molecular and cellular mechanisms underlying these processes. We show that insulin and Notch ligands directly stimulate cap cells to maintain their numbers and indirectly promote GSC maintenance. We also report that insulin signaling, via phosphoinositide 3-kinase and FOXO, intrinsically controls the competence of cap cells to respond to Notch ligands and thereby be maintained. Contrary to a previous report, we also find that Notch ligands originated in GSCs are not required either for Notch activation in the GSC niche, or for cap cell or GSC maintenance. Instead, the niche itself produces ligands that activate Notch signaling within cap cells, promoting stability of the GSC niche. Finally, insulin signals control cap cell-GSC attachment independently of their role in Notch signaling. These results are potentially relevant to many systems in which Notch signaling modulates stem cells and demonstrate that complex interactions between local and systemic signals are required for proper stem cell niche function.

  1. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?

    PubMed

    Plaks, Vicki; Kong, Niwen; Werb, Zena

    2015-03-01

    Cancer stem cells (CSCs) are tumor cells that have the principal properties of self-renewal, clonal tumor initiation capacity, and clonal long-term repopulation potential. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of CSCs, preserve their phenotypic plasticity, protect them from the immune system, and facilitate their metastatic potential. In this perspective, we focus on the CSC niche and discuss its contribution to tumor initiation and progression. Since CSCs survive many commonly employed cancer therapies, we examine the prospects of targeting the niche components as preferable therapeutic targets. PMID:25748930

  2. The Cancer Stem Cell Niche: How Essential is the Niche in Regulating Stemness of Tumor Cells?

    PubMed Central

    Plaks, Vicki; Kong, Niwen; Werb, Zena

    2015-01-01

    Cancer stem cells (CSCs) are tumor cells that have the principal properties of self-renewal, clonal tumor initiation capacity and clonal long-term repopulation potential. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of CSCs, preserve their phenotypic plasticity, protect them from the immune system and facilitate their metastatic potential. In this perspective, we focus on the CSC niche and discuss its contribution to tumor initiation and progression. Since CSCs survive many commonly employed cancer therapies, we examine the prospects of targeting the niche components as preferable therapeutic targets. PMID:25748930

  3. Cell Sorting of Neural Stem and Progenitor Cells from the Adult Mouse Subventricular Zone and Live-imaging of their Cell Cycle Dynamics.

    PubMed

    Daynac, Mathieu; Morizur, Lise; Kortulewski, Thierry; Gauthier, Laurent R; Ruat, Martial; Mouthon, Marc-André; Boussin, François D

    2015-01-01

    Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles (SVZ) sustain olfactory neurogenesis throughout life in the mammalian brain. They successively generate transit amplifying cells (TACs) and neuroblasts that differentiate into neurons once they integrate the olfactory bulbs. Emerging fluorescent activated cell sorting (FACS) techniques have allowed the isolation of NSCs as well as their progeny and have started to shed light on gene regulatory networks in adult neurogenic niches. We report here a cell sorting technique that allows to follow and distinguish the cell cycle dynamics of the above-mentioned cell populations from the adult SVZ with a LeX/EGFR/CD24 triple staining. Isolated cells are then plated as adherent cells to explore in details their cell cycle progression by time-lapse video microscopy. To this end, we use transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice in which cells are red-fluorescent during G1 phase due to a G1 specific red-Cdt1 reporter. This method has recently revealed that proliferating NSCs progressively lengthen their G1 phase during aging, leading to neurogenesis impairment. This method is easily transposable to other systems and could be of great interest for the study of the cell cycle dynamics of brain cells in the context of brain pathologies. PMID:26436641

  4. The cyclin-dependent kinase inhibitor p27 kip1 regulates radial stem cell quiescence and neurogenesis in the adult hippocampus.

    PubMed

    Andreu, Zoraida; Khan, Muhammad Amir; González-Gómez, Pilar; Negueruela, Santiago; Hortigüela, Rafael; San Emeterio, Juana; Ferrón, Sacri R; Martínez, Gloria; Vidal, Anxo; Fariñas, Isabel; Lie, Dieter Chichung; Mira, Helena

    2015-01-01

    Members of the cyclin-dependent kinase (CDK)-inhibitory protein (CIP)/kinase-inhibitory protein (KIP) family of cyclin-dependent kinase inhibitors regulate proliferation and cell cycle exit of mammalian cells. In the adult brain, the CIP/KIP protein p27(kip1) has been related to the regulation of intermediate progenitor cells located in neurogenic niches. Here, we uncover a novel function of p27(kip1) in the adult hippocampus as a dual regulator of stem cell quiescence and of cell-cycle exit of immature neurons. In vivo, p27(kip1) is detected in radial stem cells expressing SOX2 and in newborn neurons of the dentate gyrus. In vitro, the Cdkn1b gene encoding p27(kip1) is transcriptionally upregulated by quiescence signals such as BMP4. The nuclear accumulation of p27(kip1) protein in adult hippocampal stem cells encompasses the BMP4-induced quiescent state and its overexpression is able to block proliferation. p27(kip1) is also expressed in immature neurons upon differentiation of adult hippocampal stem cell cultures. Loss of p27(kip1) leads to an increase in proliferation and neurogenesis in the adult dentate gyrus, which results from both a decrease in the percentage of radial stem cells that are quiescent and a delay in cell cycle exit of immature neurons. Analysis of animals carrying a disruption in the cyclin-CDK interaction domain of p27(kip1) indicates that the CDK inhibitory function of the protein is necessary to control the activity of radial stem cells. Thus, we report that p27(kip1) acts as a central player of the molecular program that keeps adult hippocampal stem cells out of the cell cycle.

  5. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  6. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    ERIC Educational Resources Information Center

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  7. Niche-modulated and niche-modulating genes in bone marrow cells

    PubMed Central

    Cohen, Y; Garach-Jehoshua, O; Bar-Chaim, A; Kornberg, A

    2012-01-01

    Bone marrow (BM) cells depend on their niche for growth and survival. However, the genes modulated by niche stimuli have not been discriminated yet. For this purpose, we investigated BM aspirations from patients with various hematological malignancies. Each aspirate was fractionated, and the various samples were fixed at different time points and analyzed by microarray. Identification of niche-modulated genes relied on sustained change in expression following loss of niche regulation. Compared with the reference (‘authentic') samples, which were fixed immediately following aspiration, the BM samples fixed after longer stay out-of-niche acquired numerous changes in gene-expression profile (GEP). The overall genes modulated included a common subset of functionally diverse genes displaying prompt and sustained ‘switch' in expression irrespective of the tumor type. Interestingly, the ‘switch' in GEP was reversible and turned ‘off-and-on' again in culture conditions, resuming cell–cell–matrix contact versus respread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of tumor cells out-of-niche, and the regression of the ‘contactless switch' was followed by induction of a new set of genes, this time mainly encoding extracellular proteins including angiogenic factors and extracellular matrix proteins. Our data set, being unique in authentic expression design, uncovered niche-modulated and niche-modulating genes capable of controlling homing, expansion and angiogenesis. PMID:23241658

  8. Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids

    PubMed Central

    Aagesen, Lone; Biganzoli, Fernando; Bena, Julia; Godoy-Bürki, Ana C.; Reinheimer, Renata; Zuloaga, Fernando O.

    2016-01-01

    Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level. PMID:26950074

  9. Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids.

    PubMed

    Aagesen, Lone; Biganzoli, Fernando; Bena, Julia; Godoy-Bürki, Ana C; Reinheimer, Renata; Zuloaga, Fernando O

    2016-01-01

    Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.

  10. Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids.

    PubMed

    Aagesen, Lone; Biganzoli, Fernando; Bena, Julia; Godoy-Bürki, Ana C; Reinheimer, Renata; Zuloaga, Fernando O

    2016-01-01

    Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level. PMID:26950074

  11. Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus

    PubMed Central

    Lopez, Carla M.; Pelkey, Kenneth A.; Chittajallu, Ramesh; Nakashiba, Toshiaki; Tóth, Katalin; Tonegawa, Susumu; McBain, Chris J.

    2012-01-01

    In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition-based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus (DG) subfield exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs) and immature recently born GCs that are generated throughout adult life (young GCs), providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX) to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3–6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the adult brain

  12. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone

    PubMed Central

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  13. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone.

    PubMed

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  14. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone.

    PubMed

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis.

  15. Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice.

    PubMed

    Romero-Grimaldi, Carmen; Gheusi, Gilles; Lledo, Pierre-Marie; Estrada, Carmen

    2006-11-01

    The ability to generate new neurons during the course of adult life is preserved in the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus in the mammalian brain. These two regions constitute specifically regulated neurogenic niches, and provide newborn neurons involved in olfactory and spatial learning, respectively. Nitric oxide (NO) is a negative regulator of neurogenesis in the subventricular zone, whereas its role in the dentate gyrus remains controversial. Using systemic administration of NO synthase (NOS) inhibitors to chronically inhibit NO production, we increased neural precursor proliferation in the subventricular zone as well as neurogenesis in the olfactory bulb, without modifying the number of mitotic cells or the granular cell layer thickness in the dentate gyrus. The same treatment specifically improved olfactory learning performance, whereas spatial learning and memory was unchanged, thus demonstrating that olfactory memory is closely associated with the level of ongoing neurogenesis in the subventricular zone-olfactory bulb. The anatomical specificity of the NOS inhibitor actions was not due to differences in the availability of NO, as demonstrated by immunohistochemical detection of neuronal NOS and S-nitrosylated proteins in both regions. Remarkably, the distinct NO sensitivity might result from a differential expression of epidermal growth factor receptor in precursor cells in both regions, as the proliferative effect of NOS inhibitors in the subventricular zone was restricted to the cells that expressed this receptor.

  16. miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction

    PubMed Central

    Woodbury, Maya E.; Freilich, Robert W.; Cheng, Christopher J.; Asai, Hirohide; Ikezu, Seiko; Boucher, Jonathan D.; Slack, Frank

    2015-01-01

    Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development. PMID:26134658

  17. 5-HT7 receptors are involved in neurogenic dural vasodilatation in an experimental model of migraine.

    PubMed

    Wang, Xiaojuan; Fang, Yannan; Liang, Jianbo; Yan, Miansheng; Hu, Rong; Pan, Xiaoping

    2014-01-01

    Neurogenic dural vasodilation has been demonstrated to play an important role in migraine. 5-HT(7) receptors have been found on trigeminal nerve endings and middle meningeal arteries and demonstrated involved in the dilatation of meningeal arteries. The aim of the present study was to demonstrate whether 5-HT(7) receptors are involved in neurogenic dural vasodilation in migraine. The neurogenic dural vasodilation model of migraine was used in this study. Unilateral electrical stimulation of dura mater was performed in anesthetized male Sprague-Dawley rats. Animals were pretreated with selective 5-HT(7) receptor agonist AS19, 5-HT(7) receptor antagonist SB269970, 5-HT1B/1D receptor agonist sumatriptan, or vehicles. Blood flow of the middle meningeal artery (MMA) was measured by a laser Doppler flowmetry. AS19 significantly increased the basal and stimulated blood flows of the middle meningeal artery following electrical stimulation of dura mater, and its effect was dose dependent at the early stage. SB269970 and sumatriptan significantly reduced the basal and stimulated blood flows of middle meningeal artery. The present study demonstrates for the first time that 5-HT(7) receptors are involved in neurogenic dural vasodilation evoked by electrical stimulation of dura mater and maybe of relevance in the pathophysiology and treatment of migraine.

  18. Ruptured spinal arteriovenous malformation: Presenting as stunned myocardium and neurogenic shock

    PubMed Central

    Mehesry, Tasneem H.; Shaikh, Nissar; Malmstrom, Mohammad F.; Marcus, Marco A. E.; Khan, Adnan

    2015-01-01

    Background: Neurogenic pulmonary edema (NPE) is a clinical syndrome usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. NPE was identified 100 years ago, but it is still underappreciated in the clinical setup. NPE usually appears within minutes to hours after the injury. It has a high mortality rate if not recognized early and treated appropriately. Similarly, neurogenic shock is a known complication of spinal cord injury reported incidence is more than 20% in isolated upper cervical spinal injury. But NPE is rare to occur, and stunned myocardium (SM) is not reported in spinal arteriovenous malformation (AVM) rupture. SM is a reversible cardiomyopathy resulting in transient left ventricular dysfunction which has been described to occur in the setting of catecholamine release during situations of physiologic stress. We report a case of high spinal AVM rupture presenting as SM, NPE, and neurogenic shock. Case Description: A 32-year-old male who presented with sudden onset of pain and weakness in upper limbs. Imaging studies showed AVM rupture by imaging techniques. Initially, the patient had severe hypertension, respiratory distress requiring intubation and ventilation, then he developed hypotension, bradycardia, and asystole, which required immediate cardiopulmonary resuscitation and atropine. He remained with quadriplegia and suffered from frequent episodes of bradycardia and asystole. Conclusions: Spinal AVM rupture can present as neurogenic shock, stunned myocardium, and pulmonary edema. Early recognition of AVM rupture and prompt surgical intervention, as well as aggressive treatment of shock, may enhance recovery and decrease the long-term morbidity. PMID:26539315

  19. miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction.

    PubMed

    Woodbury, Maya E; Freilich, Robert W; Cheng, Christopher J; Asai, Hirohide; Ikezu, Seiko; Boucher, Jonathan D; Slack, Frank; Ikezu, Tsuneya

    2015-07-01

    Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development.

  20. Neurogenic Language Disorders in Children. International Association of Logopedics and Phoniatrics

    ERIC Educational Resources Information Center

    Fabbro, Franco, Ed.

    2004-01-01

    Language disorders in children are one of the most frequent causes of difficulties in communication, social interaction, learning and academic achievement. It has been estimated that over 5% of children present with some kind of language disorder. This volume illustrates the state of the art in neurogenic language disorders in children. The most…

  1. A Clinician Survey of Speech and Non-Speech Characteristics of Neurogenic Stuttering

    ERIC Educational Resources Information Center

    Theys, Catherine; van Wieringen, Astrid; De Nil, Luc F.

    2008-01-01

    This study presents survey data on 58 Dutch-speaking patients with neurogenic stuttering following various neurological injuries. Stroke was the most prevalent cause of stuttering in our patients, followed by traumatic brain injury, neurodegenerative diseases, and other causes. Speech and non-speech characteristics were analyzed separately for…

  2. The niche, biogeography and species interactions

    PubMed Central

    Wiens, John J.

    2011-01-01

    In this paper, I review the relevance of the niche to biogeography, and what biogeography may tell us about the niche. The niche is defined as the combination of abiotic and biotic conditions where a species can persist. I argue that most biogeographic patterns are created by niche differences over space, and that even ‘geographic barriers’ must have an ecological basis. However, we know little about specific ecological factors underlying most biogeographic patterns. Some evidence supports the importance of abiotic factors, whereas few examples exist of large-scale patterns created by biotic interactions. I also show how incorporating biogeography may offer new perspectives on resource-related niches and species interactions. Several examples demonstrate that even after a major evolutionary radiation within a region, the region can still be invaded by ecologically similar species from another clade, countering the long-standing idea that communities and regions are generally ‘saturated’ with species. I also describe the somewhat paradoxical situation where competition seems to limit trait evolution in a group, but does not prevent co-occurrence of species with similar values for that trait (called here the ‘competition–divergence–co-occurrence conundrum’). In general, the interface of biogeography and ecology could be a major area for research in both fields. PMID:21768150

  3. The Hematopoietic Niche in Myeloproliferative Neoplasms

    PubMed Central

    Schmitt-Graeff, Annette H.; Nitschke, Roland; Zeiser, Robert

    2015-01-01

    Specialized microanatomical areas of the bone marrow provide the signals that are mandatory for the maintenance and regulation of hematopoietic stem cells (HSCs) and progenitor cells. A complex microenvironment adjacent to the marrow vasculature (vascular niche) and close to the endosteum (endosteal niche) harbors multiple cell types including mesenchymal stromal cells and their derivatives such as CAR cells expressing high levels of chemokines C-X-C motif ligand 12 and early osteoblastic lineage cells, endothelial cells, and megakaryocytes. The characterization of the cellular and molecular networks operating in the HSC niche has opened new perspectives for the understanding of the bidirectional cross-talk between HSCs and stromal cell populations in normal and malignant conditions. A structural and functional remodeling of the niche may contribute to the development of myeloproliferative neoplasms (MPN). Malignant HSCs may alter the function and survival of MSCs that do not belong to the neoplastic clone. For example, a regression of nestin+ MSCs by apoptosis has been attributed to neuroglial damage in MPN. Nonneoplastic MSCs in turn can promote aggressiveness and drug resistance of malignant cells. In the future, strategies to counteract the pathological interaction between the niche and neoplastic HSCs may offer additional treatment strategies for MPN patients. PMID:26696752

  4. Modelling the ecological niche from functional traits

    PubMed Central

    Kearney, Michael; Simpson, Stephen J.; Raubenheimer, David; Helmuth, Brian

    2010-01-01

    The niche concept is central to ecology but is often depicted descriptively through observing associations between organisms and habitats. Here, we argue for the importance of mechanistically modelling niches based on functional traits of organisms and explore the possibilities for achieving this through the integration of three theoretical frameworks: biophysical ecology (BE), the geometric framework for nutrition (GF) and dynamic energy budget (DEB) models. These three frameworks are fundamentally based on the conservation laws of thermodynamics, describing energy and mass balance at the level of the individual and capturing the prodigious predictive power of the concepts of ‘homeostasis’ and ‘evolutionary fitness’. BE and the GF provide mechanistic multi-dimensional depictions of climatic and nutritional niches, respectively, providing a foundation for linking organismal traits (morphology, physiology, behaviour) with habitat characteristics. In turn, they provide driving inputs and cost functions for mass/energy allocation within the individual as determined by DEB models. We show how integration of the three frameworks permits calculation of activity constraints, vital rates (survival, development, growth, reproduction) and ultimately population growth rates and species distributions. When integrated with contemporary niche theory, functional trait niche models hold great promise for tackling major questions in ecology and evolutionary biology. PMID:20921046

  5. Differential expression of neurogenes among breast cancer subtypes identifies high risk patients

    PubMed Central

    Fernández-Nogueira, Patricia; Bragado, Paloma; Almendro, Vanessa; Ametller, Elisabet; Rios, Jose; Choudhury, Sibgat

    2016-01-01

    The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n=96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n=1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0.0001) and distant metastasis-free survival (p < 0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0.0001) and metastasis-free survival (p < 0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. PMID:26673618

  6. A home away from home: challenges and opportunities in engineering in vitro muscle satellite cell niches.

    PubMed

    Cosgrove, Benjamin D; Sacco, Alessandra; Gilbert, Penney M; Blau, Helen M

    2009-01-01

    Satellite cells are skeletal muscle stem cells with a principal role in postnatal skeletal muscle regeneration. Satellite cells, like many tissue-specific adult stem cells, reside in a quiescent state in an instructive, anatomically defined niche. The satellite cell niche constitutes a distinct membrane-enclosed compartment within the muscle fiber, containing a diversity of biochemical and biophysical signals that influence satellite cell function. A major limitation to the study and clinical utility of satellite cells is that upon removal from the muscle fiber and plating in traditional plastic tissue culture platforms, their muscle stem cell properties are rapidly lost. Clearly, the maintenance of stem cell function is critically dependent on in vivo niche signals, highlighting the need to create novel in vitro microenvironments that allow for the maintenance and propagation of satellite cells while retaining their potential to function as muscle stem cells. Here, we discuss how emerging biomaterials technologies offer great promise for engineering in vitro microenvironments to meet these challenges. In engineered biomaterials, signaling molecules can be presented in a manner that more closely mimics cell-cell and cell-matrix interactions, and matrices can be fabricated with diverse rigidities that approximate in vivo tissues. The development of in vitro microenvironments in which niche features can be systematically modulated will be instrumental not only to future insights into muscle stem cell biology and therapeutic approaches to muscle diseases and muscle wasting with aging, but also will provide a paradigm for the analysis of numerous adult tissue-specific stem cells.

  7. Review: corneal epithelial stem cells, their niche and wound healing.

    PubMed

    Castro-Muñozledo, Federico

    2013-01-01

    Stem cells emerged as a concept during the second half of 19(th) century, first as a theoretical entity, but then became one of the most promising research fields in cell biology. This work describes the most important characteristics of adult stem cells, including the experimental criteria used to identify them, and discusses current knowledge that led to the proposal that stem cells existed in different parts of the eye, such as the retina, lens, conjunctiva, corneal stroma, Descemet's membrane, and the subject of this review: the corneal epithelium. Evidence includes results that support the presence of corneal epithelial stem cells at the limbus, as well as the major obstacles to isolating them as pure cell populations. Part of this review describes the variation in the basement membrane composition between the limbus and the central cornea, to show the importance of the corneal stem cell niche, its structure, and the participation of extracellular matrix (ECM) components in regulating corneal stem cell compartment. Results obtained by various laboratories suggest that the extracellular matrix plays a central role in regulating stem cell commitment, corneal differentiation, and participation in corneal wound healing, in addition to other environmental signals such as cytokines and growth factors. The niche could define cell division patterns in corneal stem cell populations, establishing whether stem cells divide asymmetrically or symmetrically. Characterization and understanding of the factors that regulate corneal epithelial stem cells should open up new paths for developing new therapies and strategies for accelerating and improving corneal wound healing. PMID:23901244

  8. Satellite Cells and the Muscle Stem Cell Niche

    PubMed Central

    Yin, Hang; Price, Feodor

    2013-01-01

    Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

  9. Review: Corneal epithelial stem cells, their niche and wound healing

    PubMed Central

    2013-01-01

    Stem cells emerged as a concept during the second half of 19th century, first as a theoretical entity, but then became one of the most promising research fields in cell biology. This work describes the most important characteristics of adult stem cells, including the experimental criteria used to identify them, and discusses current knowledge that led to the proposal that stem cells existed in different parts of the eye, such as the retina, lens, conjunctiva, corneal stroma, Descemet’s membrane, and the subject of this review: the corneal epithelium. Evidence includes results that support the presence of corneal epithelial stem cells at the limbus, as well as the major obstacles to isolating them as pure cell populations. Part of this review describes the variation in the basement membrane composition between the limbus and the central cornea, to show the importance of the corneal stem cell niche, its structure, and the participation of extracellular matrix (ECM) components in regulating corneal stem cell compartment. Results obtained by various laboratories suggest that the extracellular matrix plays a central role in regulating stem cell commitment, corneal differentiation, and participation in corneal wound healing, in addition to other environmental signals such as cytokines and growth factors. The niche could define cell division patterns in corneal stem cell populations, establishing whether stem cells divide asymmetrically or symmetrically. Characterization and understanding of the factors that regulate corneal epithelial stem cells should open up new paths for developing new therapies and strategies for accelerating and improving corneal wound healing. PMID:23901244

  10. The bone marrow niche for haematopoietic stem cells.

    PubMed

    Morrison, Sean J; Scadden, David T

    2014-01-16

    Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.

  11. The bone marrow niche for haematopoietic stem cells

    PubMed Central

    Morrison, Sean J.; Scadden, David T.

    2015-01-01

    Preface Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a paradigm for understanding mammalian stem cells and their niches, yet the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Here we review progress in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum, and functional heterogeneity among perivascular microenvironments. PMID:24429631

  12. Modeling renal progenitors - defining the niche.

    PubMed

    Tanigawa, Shunsuke; Perantoni, Alan O

    2016-01-01

    Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for sustaining those progenitors have dramatically enhanced our understanding of their biology and developmental programing, prerequisites for establishing viable approaches to renal regeneration. In this article, we review the evolution of culture techniques and models for the study of metanephric development, describe the signaling mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+progenitor. PMID:26856661

  13. Stem cell maintenance in a different niche

    PubMed Central

    Ahn, Ji Yeon; Lee, Seung Tae

    2013-01-01

    To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed. PMID:23875159

  14. An interneuron progenitor maintains neurogenic potential in vivo and differentiates into GABAergic interneurons after transplantation in the postnatal rat brain

    PubMed Central

    Wang, Qi; Hong, Peiwei; Gao, Hui; Chen, Yuntian; Yang, Qi; Jiang, Mei; Li, Hedong

    2016-01-01

    Dysfunction of cortical GABAergic interneurons are involved in numerous neurological disorders including epilepsy, schizophrenia and autism; and replenishment of these cells by transplantation strategy has proven to be a feasible and effective method to help revert the symptoms in several animal models. To develop methodology of generating transplantable GABAergic interneurons for therapy, we previously reported the isolation of a v-myc-induced GABAergic interneuron progenitor clone GE6 from embryonic ganglionic eminence (GE). These cells can proliferate and form functional inhibitory synapses in culture. Here, we tested their differentiation behavior in vivo by transplanting them into the postnatal rat forebrain. We found that GE6 cells migrate extensively in the neonatal forebrain and differentiate into both neurons and glia, but preferentially into neurons when compared with a sister progenitor clone CTX8. The neurogenic potential of GE6 cells is also maintained after transplantation into a non-permissive environment such as adult cortex or when treated with inflammatory cytokine in culture. The GE6-derived neurons were able to mature in vivo as GABAergic interneurons expressing GABAergic, not glutamatergic, presynaptic puncta. Finally, we propose that v-myc-induced human interneuron progenitor clones could be an alternative cell source of transplantable GABAergic interneurons for treating related neurological diseases in future clinic. PMID:26750620

  15. Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.

    PubMed

    Wenger, Y; Buzgariu, W; Galliot, B

    2016-01-01

    Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

  16. Neurogenic differentiation of human umbilical cord mesenchymal stem cells on aligned electrospun polypyrrole/polylactide composite nanofibers with electrical stimulation

    NASA Astrophysics Data System (ADS)

    Zhou, Junfeng; Cheng, Liang; Sun, Xiaodan; Wang, Xiumei; Jin, Shouhong; Li, Junxiang; Wu, Qiong

    2016-09-01

    Adult central nervous system (CNS) tissue has a limited capacity to recover after trauma or disease. Recent medical cell therapy using polymeric biomaterialloaded stem cells with the capability of differentiation to specific neural population has directed focuses toward the recovery of CNS. Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal cells. Here we report on the fabrication of an electrospun polypyrrole/polylactide composite nanofiber film that direct or determine the fate of mesenchymal stem cells (MSCs), via combination of aligned surface topography, and electrical stimulation (ES). The surface morphology, mechanical properties and electric properties of the film were characterized. Comparing with that on random surface film, expression of neurofilament-lowest and nestin of human umbilical cord mesenchymal stemcells (huMSCs) cultured on film with aligned surface topography and ES were obviously enhanced. These results suggest that aligned topography combining with ES facilitates the neurogenic differentiation of huMSCs and the aligned conductive film can act as a potential nerve scaffold.

  17. Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells

    PubMed Central

    2016-01-01

    Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory–motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution. PMID:26598723

  18. Regulation of the neural niche by the soluble molecule Akhirin.

    PubMed

    Acharjee, Uzzal Kumar; Felemban, Athary Abdulhaleem; Riyadh, Asrafuzzaman M; Ohta, Kunimasa

    2016-06-01

    Though the adult central nervous system has been considered a comparatively static tissue with little turnover, it is well established today that new neural cells are generated throughout life. Neural stem/progenitor cells (NS/PCs) can self-renew and generate all types of neural cells. The proliferation of NS/PCs, and differentiation and fate determination of PCs are regulated by extrinsic factors such as growth factors, neurotrophins, and morphogens. Although several extrinsic factors that influence neurogenesis have already been reported, little is known about the role of soluble molecules in neural niche regulation. In this review, we will introduce the soluble molecule Akhirin and discuss its role in the eye and spinal cord during development.

  19. Elements of a neural stem cell niche derived from embryonic stem cells.

    PubMed

    Pierret, Chris; Spears, Kathleen; Morrison, Jason A; Maruniak, Joel A; Katz, Martin L; Kirk, Mark D

    2007-12-01

    Recent studies show that adult neural tissues can harbor stem cells within unique niches. In the mammalian central nervous system, neural stem cell (NSC) niches have been identified in the dentate gyrus and the subventricular zone (SVZ). Stem cells in the well-characterized SVZ exist in a microenvironment established by surrounding cells and tissue components, including transit-amplifying cells, neuroblasts, ependymal cells, blood vessels, and a basal lamina. Within this microenvironment, stem cell properties, including proliferation and differentiation, are maintained. Current NSC culture techniques often include the addition of molecular components found within the in vivo niche, such as mitogenic growth factors. Some protocols use bio-scaffolds to mimic the physical growth environment of living tissue. We describe a novel NSC culture system, derived from embryonic stem (ES) cells, that displays elements of an NSC niche in the absence of exogenously applied mitogens or complex physical scaffolding. Mouse ES cells were neuralized with retinoic acid and plated on an entactin-collagen-laminin-coated glass surface at high density (250,000 cells/cm(2)). Six to eight days after plating, complex multicellular structures consisting of heterogeneous cell types developed spontaneously. NSC and progenitor cell proliferation and differentiation continued within these structures. The identity of cellular and molecular components within the cultures was documented using RT-PCR, immunocytochemistry, and neurosphere-forming assays. We show that ES cells can be induced to form structures that exhibit key properties of a developing NSC niche. We believe this system can serve as a useful model for studies of neurogenesis and stem cell maintenance in the NSC niche as well as for applications in stem cell transplantation.

  20. Target article with commentaries: developmental niche construction.

    PubMed

    Flynn, Emma G; Laland, Kevin N; Kendal, Rachel L; Kendal, Jeremy R

    2013-03-01

    Niche construction is the modification of components of the environment through an organism's activities. Humans modify their environments mainly through ontogenetic and cultural processes, and it is this reliance on learning, plasticity and culture that lends human niche construction a special potency. In this paper we aim to facilitate discussion between researchers interested in niche construction and those interested in human cognitive development by highlighting some of the related processes. We discuss the transmission of culturally relevant information, how the human mind is a symbol-generating and artefact-devising system, and how these processes are bi-directional, with infants and children both being directed, and directing, their own development. We reflect on these in the light of four approaches: natural pedagogy, activity theory, distributed cognition and situated learning. Throughout, we highlight pertinent examples in non-humans that parallel or further explicate the processes discussed. Finally we offer three future directions; two involving the use of new techniques in the realms of neuroscience and modelling, and the third suggesting exploration of changes in the effects of niche construction across the lifespan.

  1. Bone metastasis and the metastatic niche.

    PubMed

    Ren, Guangwen; Esposito, Mark; Kang, Yibin

    2015-11-01

    The bone marrow has been long known to host a unique environment amenable to colonization by metastasizing tumor cells. Yet, the underlying molecular interactions within this specialized microenvironment which give rise to the high incidence of bone metastasis in breast and prostate cancer patients have long remained uncharacterized. With the recent description of the bone metastatic "niche," considerable focus has been placed on understanding how the bone stroma contributes to each step of metastasis. Discoveries within this field have demonstrated that when cancer cells home to the niche in which hematopoietic and mesenchymal stem/progenitor cells normally reside, a bidirectional crosstalk emerges between the tumor cells and the bone metastatic stroma. This communication modulates every step of cancer cell metastasis to the bone, including the initial homing and seeding, formation of micrometastases, outgrowth of macrometastases, and the maintenance of long-term dormancy of disseminated tumor cells in the bone. In clinical practice, targeting the bone metastatic niche is evolving into a promising avenue for the prevention of bone metastatic relapse, therapeutic resistance, and other aspects of cancer progression. Here, we review the current knowledge concerning the role of the bone metastatic niche in bone metastasis.

  2. ECRB ALCOVE AND NICHE GROUND SUPPORT ANALYSIS

    SciTech Connect

    J.W. Keifer

    1999-05-09

    The purpose of the analysis is to provide design bases for Enhanced Characterization of the Repository Block (ECRB) alcove and niche ground support drawings. The objective is to evaluate the ESF Alcove Ground Support Analysis (Ref 5.1) to determine if the calculations technically bound the ECRB alcoves and to address specific differences in the conditions and constraints.

  3. Relating habitat and climatic niches in birds.

    PubMed

    Barnagaud, Jean-Yves; Devictor, Vincent; Jiguet, Frédéric; Barbet-Massin, Morgane; Le Viol, Isabelle; Archaux, Frédéric

    2012-01-01

    Predicting species' responses to the combined effects of habitat and climate changes has become a major challenge in ecology and conservation biology. However, the effects of climatic and habitat gradients on species distributions have generally been considered separately. Here, we explore the relationships between the habitat and thermal dimensions of the ecological niche in European common birds. Using data from the French Breeding Bird Survey, a large-scale bird monitoring program, we correlated the habitat and thermal positions and breadths of 74 bird species, controlling for life history traits and phylogeny. We found that cold climate species tend to have niche positions in closed habitats, as expected by the conjunction of the biogeographic history of birds' habitats, and their current continent-scale gradients. We also report a positive correlation between thermal and habitat niche breadths, a pattern consistent with macroecological predictions concerning the processes shaping species' distributions. Our results suggest that the relationships between the climatic and habitat components of the niche have to be taken into account to understand and predict changes in species' distributions. PMID:22427891

  4. Relating Habitat and Climatic Niches in Birds

    PubMed Central

    Barnagaud, Jean-Yves; Devictor, Vincent; Jiguet, Frédéric; Barbet-Massin, Morgane; Le Viol, Isabelle; Archaux, Frédéric

    2012-01-01

    Predicting species' responses to the combined effects of habitat and climate changes has become a major challenge in ecology and conservation biology. However, the effects of climatic and habitat gradients on species distributions have generally been considered separately. Here, we explore the relationships between the habitat and thermal dimensions of the ecological niche in European common birds. Using data from the French Breeding Bird Survey, a large-scale bird monitoring program, we correlated the habitat and thermal positions and breadths of 74 bird species, controlling for life history traits and phylogeny. We found that cold climate species tend to have niche positions in closed habitats, as expected by the conjunction of the biogeographic history of birds' habitats, and their current continent-scale gradients. We also report a positive correlation between thermal and habitat niche breadths, a pattern consistent with macroecological predictions concerning the processes shaping species' distributions. Our results suggest that the relationships between the climatic and habitat components of the niche have to be taken into account to understand and predict changes in species' distributions. PMID:22427891

  5. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features.

    PubMed

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-06-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution. PMID:25882650

  6. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features.

    PubMed

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-06-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.

  7. Diet and niche overlap of southern populations of brill Scophthalmus rhombus and turbot Scophthalmus maximus.

    PubMed

    Vinagre, C; Silva, A; Lara, M; Cabral, H N

    2011-11-01

    The diets of adult brill Scophthalmus rhombus and turbot Scophthalmus maximus from the Portuguese coast relied mostly on fishes. There was a higher diversity of food items compared to their northern counterparts, and several of the identified prey are the first records of these species, including a brown alga, echinoderms, nematodes, oligochaetes, gastropods, bivalves and various fish species. The diet of the two species was significantly different and niche overlap was low. PMID:22026615

  8. Functional traits, convergent evolution, and periodic tables of niches.

    PubMed

    Winemiller, Kirk O; Fitzgerald, Daniel B; Bower, Luke M; Pianka, Eric R

    2015-08-01

    Ecology is often said to lack general theories sufficiently predictive for applications. Here, we examine the concept of a periodic table of niches and feasibility of niche classification schemes from functional trait and performance data. Niche differences and their influence on ecological patterns and processes could be revealed effectively by first performing data reduction/ordination analyses separately on matrices of trait and performance data compiled according to logical associations with five basic niche 'dimensions', or aspects: habitat, life history, trophic, defence and metabolic. Resultant patterns then are integrated to produce interpretable niche gradients, ordinations and classifications. Degree of scheme periodicity would depend on degrees of niche conservatism and convergence causing species clustering across multiple niche dimensions. We analysed a sample data set containing trait and performance data to contrast two approaches for producing niche schemes: species ordination within niche gradient space, and niche categorisation according to trait-value thresholds. Creation of niche schemes useful for advancing ecological knowledge and its applications will depend on research that produces functional trait and performance datasets directly related to niche dimensions along with criteria for data standardisation and quality. As larger databases are compiled, opportunities will emerge to explore new methods for data reduction, ordination and classification. PMID:26096695

  9. Realized niche shift during a global biological invasion

    PubMed Central

    Tingley, Reid; Vallinoto, Marcelo; Sequeira, Fernando; Kearney, Michael R.

    2014-01-01

    Accurate forecasts of biological invasions are crucial for managing invasion risk but are hampered by niche shifts resulting from evolved environmental tolerances (fundamental niche shifts) or the presence of novel biotic and abiotic conditions in the invaded range (realized niche shifts). Distinguishing between these kinds of niche shifts is impossible with traditional, correlative approaches to invasion forecasts, which exclusively consider the realized niche. Here we overcome this challenge by combining a physiologically mechanistic model of the fundamental niche with correlative models based on the realized niche to study the global invasion of the cane toad Rhinella marina. We find strong evidence that the success of R. marina in Australia reflects a shift in the species’ realized niche, as opposed to evolutionary shifts in range-limiting traits. Our results demonstrate that R. marina does not fill its fundamental niche in its native South American range and that areas of niche unfilling coincide with the presence of a closely related species with which R. marina hybridizes. Conversely, in Australia, where coevolved taxa are absent, R. marina largely fills its fundamental niche in areas behind the invasion front. The general approach taken here of contrasting fundamental and realized niche models provides key insights into the role of biotic interactions in shaping range limits and can inform effective management strategies not only for invasive species but also for assisted colonization under climate change. PMID:24982155

  10. Functional traits, convergent evolution, and periodic tables of niches.

    PubMed

    Winemiller, Kirk O; Fitzgerald, Daniel B; Bower, Luke M; Pianka, Eric R

    2015-08-01

    Ecology is often said to lack general theories sufficiently predictive for applications. Here, we examine the concept of a periodic table of niches and feasibility of niche classification schemes from functional trait and performance data. Niche differences and their influence on ecological patterns and processes could be revealed effectively by first performing data reduction/ordination analyses separately on matrices of trait and performance data compiled according to logical associations with five basic niche 'dimensions', or aspects: habitat, life history, trophic, defence and metabolic. Resultant patterns then are integrated to produce interpretable niche gradients, ordinations and classifications. Degree of scheme periodicity would depend on degrees of niche conservatism and convergence causing species clustering across multiple niche dimensions. We analysed a sample data set containing trait and performance data to contrast two approaches for producing niche schemes: species ordination within niche gradient space, and niche categorisation according to trait-value thresholds. Creation of niche schemes useful for advancing ecological knowledge and its applications will depend on research that produces functional trait and performance datasets directly related to niche dimensions along with criteria for data standardisation and quality. As larger databases are compiled, opportunities will emerge to explore new methods for data reduction, ordination and classification.

  11. Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

    PubMed Central

    Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David; Sanberg, Paul R.; Bickford, Paula C.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes. PMID:23301065

  12. [Reparative Neurogenesis in the Brain and Changes in the Optic Nerve of Adult Trout Oncorhynchus mykiss after Mechanical Damage of the Eye].

    PubMed

    Puschina, E V; Varaksin, A A; Obukhov, D K

    2016-01-01

    Reparative proliferation and neurogenesis in the brain integrative centers after mechanical eye injury in an adult trout Oncorhynchus mykiss have been studied. We have found that proliferation and neurogenesis in proliferative brain regions, the cerebellum, and the optic tectum were significantly enhanced after the eye injury. The cerebellum showed a significant increase in the proliferative activity of the cells of the dorsal proliferative zone and parenchymal cells of the molecular and granular layers. One week after the injury, PCNA-positive radial glia cells have been identified in the tectum. We have found for the first time that the eye trauma resulted in the development of local clusters of undifferentiated cells forming so called neurogenic niches in the tectum and cerebellum. The differentiation of neuronal cells detected by labeling cells with antibodies against the protein HuC/D occurred in the proliferative zones of the telencephalon, the optic tectum, cerebellum, and medulla of a trout within 2 days after the injury. We have shown that the HuC/D expression is higher in the proliferative brain regions than in the definitive neurons of a trout. In addition, we have examined cell proliferation, migration, and apoptosis caused by the eye injury in the contra- and ipsilateral optic nerves and adjacent muscle fibers 2 days after the trauma. The qualitative and quantitative assessment of proliferation and apoptosis in the cells of the optic nerve of a trout has been made using antibodies against PCNA and the TUNEL method. PMID:27149746

  13. Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children.

    PubMed

    Bajpai, Anurag; Sharma, Jyoti; Kabra, Madhulika; Kumar Gupta, Arun; Menon, P S N

    2002-01-01

    The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age

  14. Emphysematous Pyelonephritis Caused by Citrobacter freundii in a Patient with Type 2 Diabetes and Neurogenic Bladder.

    PubMed

    Kim, Min Jeong; Park, Ji Sang; Lim, Hye Jin; Jung, Jihye; Shin, Dong Geum; Lee, Ki-Deok; Jung, Yoon Young; Min, Kyung Wan; Han, Kyung-Ah

    2013-09-01

    Emphysematous pyelonephritis (EPN) is a rare, life-threatening complication of upper urinary tract infections that is characterized by the presence of gas in the renal parenchyma and perirenal space. It commonly occurs in diabetic patients. Escherichia coli are the most common causative organisms, with few reports implicating Citrobacter freundii as the etiologic agent in EPN. A 57-year-old woman with diabetes and neurogenic bladder visited at our department with confused mentality, myalgia, and general weakness. Further investigation revealed that the patient suffered from unilateral EPN with sepsis caused by C. freundii. The patient's condition was improved considerably with percutaneous drainage and use of intravenous antibiotics for several weeks. However, renal function eventually deteriorated to permanent renal failure, which required hemodialysis. In conclusion, C. freundii may be the causative pathogen of EPN in a patient with type 2 diabetes and neurogenic bladder.

  15. Evaluation and Management of Neurogenic Bladder: What Is New in China?

    PubMed Central

    Liao, Limin

    2015-01-01

    Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central nervous system or peripheral nerves, is a major global medical and social problem. Numerous nervous system abnormalities, such as: stroke, Alzheimer’s and Parkinson’s diseases, traumatic spinal cord injury, spinal cord tumors, congenital spina bifida, and diabetes, can cause NB/NLUTD. There are two major types of bladder control problems associated with NB/NLUTD: the bladder becomes either overactive or underactive depending on the nature, level, and extent of nerve damage. This review specifically focuses on the diagnosis and management of NB/NLUTD in China as well as on recent efforts to treat this disease. PMID:26266405

  16. A Case of Neuro-Behcet’s Disease Presenting with Central Neurogenic Hyperventilation

    PubMed Central

    Alkhachroum, Ayham M.; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; De Georgia, Michael A.

    2016-01-01

    Patient: Female, 46 Final Diagnosis: Central hyperventilation Symptoms: Hyperventilation Medication: — Clinical Procedure: None Specialty: Neurology Objective: Unusual clinical course Background: Behcet’s disease is a chronic inflammatory disorder usually characterized by the triad of oral ulcers, genital ulcers, and uveitis. Central to the pathogenesis of Behcet’s disease is an autoimmune vasculitis. Neurological involvement, so called “Neuro-Behcet’s disease”, occurs in 10–20% of patients, usually from a meningoencephalitis or venous thrombosis. Case Report: We report the case of a 46-year-old patient with Neuro-Behcet’s disease who presented with central neurogenic hyperventilation as a result of brainstem involvement from venulitis. Conclusions: To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet’s disease. PMID:26965646

  17. Evaluation and Management of Neurogenic Bladder: What Is New in China?

    PubMed

    Liao, Limin

    2015-01-01

    Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central nervous system or peripheral nerves, is a major global medical and social problem. Numerous nervous system abnormalities, such as: stroke, Alzheimer's and Parkinson's diseases, traumatic spinal cord injury, spinal cord tumors, congenital spina bifida, and diabetes, can cause NB/NLUTD. There are two major types of bladder control problems associated with NB/NLUTD: the bladder becomes either overactive or underactive depending on the nature, level, and extent of nerve damage. This review specifically focuses on the diagnosis and management of NB/NLUTD in China as well as on recent efforts to treat this disease. PMID:26266405

  18. N-Docosahexaenoylethanolamine ameliorates ethanol-induced impairment of neural stem cell neurogenic differentiation.

    PubMed

    Rashid, Mohammad Abdur; Kim, Hee-Yong

    2016-03-01

    Previous studies demonstrated that prenatal exposure to ethanol interferes with embryonic and fetal development, and causes abnormal neurodevelopment. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid highly enriched in the brain, was shown to be essential for proper brain development and function. Recently, we found that N-docosahexenoyethanolamine (synaptamide), an endogenous metabolite of DHA, is a potent PKA-dependent neurogenic factor for neural stem cell (NSC) differentiation. In this study, we demonstrate that ethanol at pharmacologically relevant concentrations downregulates cAMP signaling in NSC and impairs neurogenic differentiation. In contrast, synaptamide reverses ethanol-impaired NSC neurogenic differentiation through counter-acting on the cAMP production system. NSC exposure to ethanol (25-50 mM) for 4 days dose-dependently decreased the number of Tuj-1 positive neurons and PKA/CREB phosphorylation with a concomitant reduction of cellular cAMP. Ethanol-induced cAMP reduction was accompanied by the inhibition of G-protein activation and expression of adenylyl cyclase (AC) 7 and AC8, as well as PDE4 upregulation. In contrast to ethanol, synaptamide increased cAMP production, GTPγS binding, and expression of AC7 and AC8 isoforms in a cAMP-dependent manner, offsetting the ethanol-induced impairment in neurogenic differentiation. These results indicate that synaptamide can reduce ethanol-induced impairment of neuronal differentiation by counter-affecting shared targets in G-protein coupled receptor (GPCR)/cAMP signaling. The synaptamide-mediated mechanism observed in this study may offer a possible avenue for ameliorating the adverse impact of fetal alcohol exposure on neurodevelopment. PMID:26586023

  19. Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries.

    PubMed

    Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y; Lua, Ahai Chang; Lee, Tony Jer-Fu

    2016-08-15

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation

  20. N-Docosahexaenoylethanolamine ameliorates ethanol-induced impairment of neural stem cell neurogenic differentiation.

    PubMed

    Rashid, Mohammad Abdur; Kim, Hee-Yong

    2016-03-01

    Previous studies demonstrated that prenatal exposure to ethanol interferes with embryonic and fetal development, and causes abnormal neurodevelopment. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid highly enriched in the brain, was shown to be essential for proper brain development and function. Recently, we found that N-docosahexenoyethanolamine (synaptamide), an endogenous metabolite of DHA, is a potent PKA-dependent neurogenic factor for neural stem cell (NSC) differentiation. In this study, we demonstrate that ethanol at pharmacologically relevant concentrations downregulates cAMP signaling in NSC and impairs neurogenic differentiation. In contrast, synaptamide reverses ethanol-impaired NSC neurogenic differentiation through counter-acting on the cAMP production system. NSC exposure to ethanol (25-50 mM) for 4 days dose-dependently decreased the number of Tuj-1 positive neurons and PKA/CREB phosphorylation with a concomitant reduction of cellular cAMP. Ethanol-induced cAMP reduction was accompanied by the inhibition of G-protein activation and expression of adenylyl cyclase (AC) 7 and AC8, as well as PDE4 upregulation. In contrast to ethanol, synaptamide increased cAMP production, GTPγS binding, and expression of AC7 and AC8 isoforms in a cAMP-dependent manner, offsetting the ethanol-induced impairment in neurogenic differentiation. These results indicate that synaptamide can reduce ethanol-induced impairment of neuronal differentiation by counter-affecting shared targets in G-protein coupled receptor (GPCR)/cAMP signaling. The synaptamide-mediated mechanism observed in this study may offer a possible avenue for ameliorating the adverse impact of fetal alcohol exposure on neurodevelopment.

  1. From the archives of the AFIP. Imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation.

    PubMed

    Murphey, M D; Smith, W S; Smith, S E; Kransdorf, M J; Temple, H T

    1999-01-01

    Numerous neurogenic tumors can affect the musculoskeletal system, including traumatic neuroma, Morton neuroma, neural fibrolipoma, nerve sheath ganglion, neurilemoma, neurofibroma, and malignant peripheral nerve sheath tumors (PNSTs). The diagnosis of neurogenic tumors can be suggested from their imaging appearances, including lesion shape and intrinsic imaging characteristics. It is also important to establish lesion location along a typical nerve distribution (eg, plantar digital nerve in Morton neuroma, median nerve in neural fibrolipoma, large nerve trunk in benign and malignant PNSTs). Traumatic and Morton neuromas are commonly related to an amputation stump or are located in the intermetatarsal space, respectively. Neural fibrolipomas show fat interspersed between nerve fascicles and are often associated with macrodactyly. Nerve sheath ganglion has a cystic appearance and commonly occurs about the knee. Radiologic characteristics of neurilemoma, neurofibroma, and malignant PNST at computed tomography (CT), ultrasonography, and magnetic resonance imaging include fusiform shape, identification of entering and exiting nerve, low attenuation at CT, target sign, fascicular sign, split-fat sign, and associated muscle atrophy. Although differentiation of neurilemoma from neurofibroma and of benign from malignant PNST is problematic, recognition of the radiologic appearances of neurogenic tumors often allows prospective diagnosis and improves clinical management of patients.

  2. Changes of neural markers expression during late neurogenic differentiation of human adipose-derived stem cells

    PubMed Central

    Razavi, Shahnaz; Khosravizadeh, Zahra; Bahramian, Hamid; Kazemi, Mohammad

    2015-01-01

    Background: Different studies have been done to obtain sufficient number of neural cells for treatment of neurodegenerative diseases, spinal cord, and traumatic brain injury because neural stem cells are limited in central nerves system. Recently, several studies have shown that adipose-derived stem cells (ADSCs) are the appropriate source of multipotent stem cells. Furthermore, these cells are found in large quantities. The aim of this study was an assessment of proliferation and potential of neurogenic differentiation of ADSCs with passing time. Materials and Methods: Neurosphere formation was used for neural induction in isolated human ADSCs (hADSCs). The rate of proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and potential of neural differentiation of induced hADSCs was evaluated by immunocytochemical and real-time reverse transcription polymerase chain reaction analysis after 10 and 14 days post-induction. Results: The rate of proliferation of induced hADSCs increased after 14 days while the expression of nestin, glial fibrillary acidic protein, and microtubule-associated protein 2 was decreased with passing time during neurogenic differentiation. Conclusion: These findings showed that the proliferation of induced cells increased with passing time, but in early neurogenic differentiation of hADSCs, neural expression was higher than late of differentiation. Thus, using of induced cells in early differentiation may be suggested for in vivo application. PMID:26605238

  3. Neurogenic pruritus: an unrecognised problem? A retrospective case series of treatment by acupuncture.

    PubMed

    Stellon, Anthony

    2002-12-01

    Intractable localised segmental pruritus without a rash has been reported over the years under various titles depending on the area of the body affected. Notalgia paresthetica and brachioradial pruritus are the two terms used for what is believed to be a form of neuropathy. The clinical observations reported here suggest that other localised cases of pruritus exist that share common clinical features, and the term neurogenic pruritus is suggested to encompass these under one clinical condition. Acupuncture has been used to treat skin conditions, of which pruritus is one symptom. This retrospective study looked at the symptomatic relief of neurogenic pruritus in 16 patients using acupuncture. In 12 cases the affected dermatomes of the body were innervated by cervical spinal nerves, seven innervated by dorsal spinal nerves and four innervated by the lumbar spinal nerves. Seven patients had areas affected by two different regions of the spine. Restricted neck or back movements were noted in patients as were areas of paravertebral spasm or tenderness of the muscles. Total resolution of symptoms as judged by VAS occurred in 75% of patients. Relapse occurred in 37% of patients within 1-12 months following treatment. Acupuncture appeared to be effective in alleviating the distressing symptom of itching in patients presenting with neurogenic pruritus. PMID:12512793

  4. Complications of untreated and ineffectively treated neurogenic bladder dysfunctions in children: our own practical classification.

    PubMed

    Kroll, P; Zachwieja, J

    2016-04-01

    The neurogenic dysfunctions of the detrusor and the sphincter are caused by either a known congenital defect of the nervous system or by acquired damage to the nervous system. In patients with idiopathic bladder dysfunctions neurological examinations fail to reveal any pathology in the nervous system. The treatment strategy for the patient with detrusor-sphincter dysfunction should be based on a comprehensive functional and morphological evaluation. Clean Intermittent Catheterization is mandatory if voiding is ineffective. Reduced bladder capacity related to detrusor overactivity and decreased bladder walls compliance is successfully managed conservatively with oral anticholinergics. Conservative treatment prevents complications in the majority of patients. However, despite proper conservative treatment, some patients still develop complications. We propose our own practical classification of complications characteristic for the bladder and sphincter dysfunctions: 1. Urinary tract infections; 2. Urolithiasis; 3. Anatomic changes in the lower urinary tract; 4. Anatomic changes in the upper urinary tract; 5. Functional disturbances of kidneys parenchyma; 6. Urinary incontinence. Proposed practical classification of complications of bladder and sphincter dysfunctions is clear and simple. This classification can be used both in children with neurogenic and non-neurogenic dysfunctions. It is helpful in planning follow-up procedures and evaluation of treatment results. PMID:27097940

  5. Normal and Leukemic Stem Cell Niches: Insights and Therapeutic Opportunities

    PubMed Central

    Schepers, Koen; Campbell, Timothy B.; Passegué, Emmanuelle

    2015-01-01

    Hematopoietic stem cells (HSC) rely on instructive cues from the bone marrow (BM) niche to maintain their quiescence and adapt blood production to the organism’s needs. Alterations in the BM niche are commonly observed in blood malignancies and directly contribute to the aberrant function of disease-initiating leukemic stem cells (LSC). Here, we review recent insights into the cellular and molecular determinants of the normal HSC niche and describe how genetic changes in stromal cells and leukemia-induced BM niche remodeling contribute to blood malignancies. Moreover, we discuss how these findings can be applied to non cell-autonomous therapies targeting the LSC niche. PMID:25748932

  6. Tooth, hair and claw: comparing epithelial stem cell niches of ectodermal appendages.

    PubMed

    Naveau, Adrien; Seidel, Kerstin; Klein, Ophir D

    2014-07-15

    The vertebrate ectoderm gives rise to organs that produce mineralized or keratinized substances, including teeth, hair, and claws. Most of these ectodermal derivatives grow continuously throughout the animal׳s life and have active pools of adult stem cells that generate all the necessary cell types. These organs provide powerful systems for understanding the mechanisms that enable stem cells to regenerate or renew ectodermally derived tissues, and remarkable progress in our understanding of these systems has been made in recent years using mouse models. We briefly compare what is known about stem cells and their niches in incisors, hair follicles, and claws, and we examine expression of Gli1 as a potential example of a shared stem cell marker. We summarize some of the features, structures, and functions of the stem cell niches in these ectodermal derivatives; definition of the basic elements of the stem cell niches in these organs will provide guiding principles for identification and characterization of the niche in similar systems.

  7. Tooth, hair and claw: comparing epithelial stem cell niches of ectodermal appendages

    PubMed Central

    Naveau, Adrien; Seidel, Kerstin; Klein, Ophir D.

    2014-01-01

    The vertebrate ectoderm gives rise to organs that produce mineralized or keratinized substances, including teeth, hair, and claws. Most of these ectodermal derivatives grow continuously throughout the animal’s life and have active pools of adult stem cells that generate all the necessary cell types. These organs provide powerful systems for understanding the mechanisms that enable stem cells to regenerate or renew ectodermally derived tissues, and remarkable progress in our understanding of these systems has been made in recent years using mouse models. We briefly compare what is known about stem cells and their niches in incisors, hair follicles, and claws, and we examine expression of Gli1 as a potential example of a shared stem cell marker. We summarize some of the features, structures, and functions of the stem cell niches in these ectodermal derivatives; definition of the basic elements of the stem cell niches in these organs will provide guiding principles for identification and characterization of the niche in similar systems. PMID:24530577

  8. Parent stem cells can serve as niches for their daughter cells.

    PubMed

    Pardo-Saganta, Ana; Tata, Purushothama Rao; Law, Brandon M; Saez, Borja; Chow, Ryan Dz-Wei; Prabhu, Mythili; Gridley, Thomas; Rajagopal, Jayaraj

    2015-07-30

    Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation. Recently, stem cells have been shown to regulate themselves using an autocrine mechanism. The existence of a 'stem cell niche' was first postulated by Schofield in 1978 to define local environments necessary for the maintenance of haematopoietic stem cells. Since then, an increasing body of work has focused on defining stem cell niches. Yet little is known about how progenitor cell and differentiated cell numbers and proportions are maintained. In the airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory cells and ciliated cells. Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells . Here we describe a mode of cell regulation in which adult mammalian stem/progenitor cells relay a forward signal to their own progeny. Surprisingly, this forward signal is shown to be necessary for daughter cell maintenance. Using a combination of cell ablation, lineage tracing and signalling pathway modulation, we show that airway basal stem/progenitor cells continuously supply a Notch ligand to their daughter secretory cells. Without these forward signals, the secretory progenitor cell pool fails to be maintained and secretory cells execute a terminal differentiation program and convert into ciliated cells. Thus, a parent stem/progenitor cell can serve as a functional daughter cell niche.

  9. Hepatogenic and neurogenic differentiation of bone marrow mesenchymal stem cells from abattoir-derived bovine fetuses

    PubMed Central

    2014-01-01

    Background Mesenchymal stem cells (MSC) are multipotent progenitor cells characterized by their ability to both self-renew and differentiate into tissues of mesodermal origin. The plasticity or transdifferentiation potential of MSC is not limited to mesodermal derivatives, since under appropriate cell culture conditions and stimulation by bioactive factors, MSC have also been differentiated into endodermal (hepatocytes) and neuroectodermal (neurons) cells. The potential of MSC for hepatogenic and neurogenic differentiation has been well documented in different animal models; however, few reports are currently available on large animal models. In the present study we sought to characterize the hepatogenic and neurogenic differentiation and multipotent potential of bovine MSC (bMSC) isolated from bone marrow (BM) of abattoir-derived fetuses. Results Plastic-adherent bMSC isolated from fetal BM maintained a fibroblast-like morphology under monolayer culture conditions. Flow cytometric analysis demonstrated that bMSC populations were positive for MSC markers CD29 and CD73 and pluripotency markers OCT4 and NANOG; whereas, were negative for hematopoietic markers CD34 and CD45. Levels of mRNA of hepatic genes α-fetoprotein (AFP), albumin (ALB), alpha1 antitrypsin (α1AT), connexin 32 (CNX32), tyrosine aminotransferase (TAT) and cytochrome P450 (CYP3A4) were up-regulated in bMSC during a 28-Day period of hepatogenic differentiation. Functional analyses in differentiated bMSC cultures evidenced an increase (P < 0.05) in albumin and urea production and glycogen storage. bMSC cultured under neurogenic conditions expressed NESTIN and MAP2 proteins at 24 h of culture; whereas, at 144 h also expressed TRKA and PrPC. Levels of MAP2 and TRKA mRNA were up-regulated at the end of the differentiation period. Conversely, bMSC expressed lower levels of NANOG mRNA during both hepatogenic and neurogenic differentiation processes. Conclusion The expression patterns of linage

  10. A synthetic niche for nephron progenitor cells.

    PubMed

    Brown, Aaron C; Muthukrishnan, Sree Deepthi; Oxburgh, Leif

    2015-07-27

    FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fold in this environment can be induced to form tubules expressing nephron differentiation markers. Single-cell culture reveals phenotypic variability within the early CITED1-expressing NPC compartment, indicating that it is a mixture of cells with varying progenitor potential. Furthermore, we find that the developmental age of NPCs does not correlate with propagation capacity, indicating that cessation of nephrogenesis is related to factors other than an intrinsic clock. This in vitro nephron progenitor niche will have important applications for expansion of cells for engraftment and will facilitate investigation of mechanisms that determine the balance between renewal and differentiation in these cells. PMID:26190145

  11. Mammalian niche conservation through deep time.

    PubMed

    DeSantis, Larisa R G; Beavins Tracy, Rachel A; Koontz, Cassandra S; Roseberry, John C; Velasco, Matthew C

    2012-01-01

    Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas) are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of terminal Pleistocene

  12. Drug addiction finds its own niche.

    PubMed

    Reid, Alastair

    2011-12-01

    The evolutionary framework suggested by Müller & Schumann (M&S) can be extended further by considering drug-taking in terms of Niche Construction Theory (NCT). It is suggested here that genetic and environmental components of addiction are modified by cultural acceptance of the advantages of non-addicted drug taking and the legitimate supply of performance-enhancing drugs. This may then reduce the prevalence of addiction.

  13. Engineering stem cell niches in bioreactors

    PubMed Central

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering. PMID:24179601

  14. PEDF & stem cells: niche vs. nurture.

    PubMed

    Fitchev, Philip; Chung, Chuhan; Plunkett, Beth A; Brendler, Charles B; Crawford, Susan E

    2014-01-01

    Anti-angiogenic pigment epithelium-derived factor (PEDF) is a multifunctional 50kD secreted glycoprotein emerging as a key factor in stem cell renewal. Characteristics of the stem cell niche can be highly dependent on location, access to the vasculature, oxygen tension and neighboring cells. In the neural stem cell (NSC) niche, specifically the subventricular zone, PEDF actively participates in the self renewal process and promotes stemness by upregulating Notch signaling effectors Hes1 and Hes5. The local vascular endothelial cells and ependymal cells are the likely sources of PEDF for the NSC while mesenchymal and retinal stem cells can actually produce PEDF. The opposing actions of PEDF and VEGF on various cells are recapitulated in the NSC niche. Intraventricular injection of PEDF promotes stem cell renewal, while injection of VEGF prompts differentiation and neurogenesis in the subventricular zone. Enhancing the expression of PEDF in stem cells has promising therapeutic implications. Bone marrow mesenchymal stem cells overexpressing PEDF effectively inhibited pathologic angiogenesis in the murine eye and these same cells suppressed hepatocellular carcinoma growth. As a protein with bioactivities in nearly all normal organ systems, it is likely that PEDF will continue to gain visibility as an essential component in the development and delivery of novel stem cell-based therapies to combat disease.

  15. Neutral biogeography and the evolution of climatic niches.

    PubMed

    Boucher, Florian C; Thuiller, Wilfried; Davies, T Jonathan; Lavergne, Sébastien

    2014-05-01

    Recent debate on whether climatic niches are conserved through time has focused on how phylogenetic niche conservatism can be measured by deviations from a Brownian motion model of evolutionary change. However, there has been no evaluation of this methodological approach. In particular, the fact that climatic niches are usually obtained from distribution data and are thus heavily influenced by biogeographic factors has largely been overlooked. Our main objective here was to test whether patterns of climatic niche evolution that are frequently observed might arise from neutral dynamics rather than from adaptive scenarios. We developed a model inspired by neutral biodiversity theory, where individuals disperse, compete, and undergo speciation independently of climate. We then sampled the climatic niches of species according to their geographic position and showed that even when species evolve independently of climate, their niches can nonetheless exhibit evolutionary patterns strongly differing from Brownian motion. Indeed, climatic niche evolution is better captured by a model of punctuated evolution with constraints due to landscape boundaries, two features that are traditionally interpreted as evidence for selective processes acting on the niche. We therefore suggest that deviation from Brownian motion alone should not be used as evidence for phylogenetic niche conservatism but that information on phenotypic traits directly linked to physiology is required to demonstrate that climatic niches have been conserved through time. PMID:24739191

  16. Neutral biogeography and the evolution of climatic niches

    PubMed Central

    Boucher, Florian C.; Thuiller, Wilfried; Davies, T. Jonathan; Lavergne, Sébastien

    2014-01-01

    Recent debate on whether climatic niches are conserved through time has focused on how phylogenetic niche conservatism can be measured by deviations from a Brownian motion model of evolutionary change. However, there has been no evaluation of this methodological approach. In particular, the fact that climatic niches are usually obtained from distribution data and are thus heavily influenced by biogeographic factors has largely been overlooked. Our main objective here was to test whether patterns of climatic niche evolution that are frequently observed might arise from neutral dynamics rather than adaptive scenarios. We develop a model inspired by Neutral Biodiversity Theory, where individuals disperse, compete, and undergo speciation independently of climate. We then sample the climatic niches of species according to their geographic position and show that even when species evolved independently of climate, their niches can nonetheless exhibit evolutionary patterns strongly differing from Brownian motion. Indeed, climatic niche evolution is better captured by a model of punctuated evolution with constraints due to landscape boundaries, two features that are traditionally interpreted as evidence for selective processes acting on the niche. We therefore suggest that deviation from Brownian motion alone should not be used as evidence for phylogenetic niche conservatism, but that information on phenotypic traits directly linked to physiology is required to demonstrate that climatic niches have been conserved through time. PMID:24739191

  17. Evolution of pollination niches in a generalist plant clade.

    PubMed

    Gómez, José María; Perfectti, Francisco; Abdelaziz, Mohamed; Lorite, Juan; Muñoz-Pajares, Antonio Jesús; Valverde, Javier

    2015-01-01

    It is widely assumed that floral diversification occurs by adaptive shifts between pollination niches. In contrast to specialized flowers, identifying pollination niches of generalist flowers is a challenge. Consequently, how generalist pollination niches evolve is largely unknown. We apply tools from network theory and comparative methods to investigate the evolution of pollination niches among generalist species belonging to the genus Erysimum. These species have similar flowers. We found that the studied species may be grouped in several multidimensional niches separated not by a shift of pollinators, but instead by quantitative variation in the relative abundance of pollinator functional groups. These pollination niches did not vary in generalization degree; we did not find any evolutionary trend toward specialization within the studied clade. Furthermore, the evolution of pollination niche fitted to a Brownian motion model without phylogenetic signal, and was characterized by frequent events of niche convergences and divergences. We presume that the evolution of Erysimum pollination niches has occurred mostly by recurrent shifts between slightly different generalized pollinator assemblages varying spatially as a mosaic and without any change in specialization degree. Most changes in pollination niches do not prompt floral divergence, a reason why adaptation to pollinators is uncommon in generalist plants.

  18. Rapid evolution of adaptive niche construction in experimental microbial populations.

    PubMed

    Callahan, Benjamin J; Fukami, Tadashi; Fisher, Daniel S

    2014-11-01

    Many species engage in adaptive niche construction: modification of the local environment that increases the modifying organism's competitive fitness. Adaptive niche construction provides an alternative pathway to higher fitness, shaping the environment rather than conforming to it. Yet, experimental evidence for the evolutionary emergence of adaptive niche construction is lacking, leaving its role in evolution uncertain. Here we report a direct observation of the de novo evolution of adaptive niche construction in populations of the bacteria Pseudomonas fluorescens. In a laboratory experiment, we allowed several bacterial populations to adapt to a novel environment and assessed whether niche construction evolved over time. We found that adaptive niche construction emerged rapidly, within approximately 100 generations, and became ubiquitous after approximately 400 generations. The large fitness effect of this niche construction was dominated by the low fitness of evolved strains in the ancestrally modified environment: evolved niche constructors were highly dependent on their specific environmental modifications. Populations were subjected to frequent resetting of environmental conditions and severe reduction of spatial habitat structure, both of which are thought to make adaptive niche construction difficult to evolve. Our finding that adaptive niche construction nevertheless evolved repeatably suggests that it may play a more important role in evolution than generally thought.

  19. Ecological and evolutionary consequences of niche construction for its agent.

    PubMed

    Kylafis, Grigoris; Loreau, Michel

    2008-10-01

    Niche construction can generate ecological and evolutionary feedbacks that have been underinvestigated so far. We present an eco-evolutionary model that incorporates the process of niche construction to reveal its effects on the ecology and evolution of the niche-constructing agent. We consider a simple plant-soil nutrient ecosystem in which plants have the ability to increase the input of inorganic nutrient as an example of positive niche construction. On an ecological time scale, the model shows that niche construction allows the persistence of plants under infertile soil conditions that would otherwise lead to their extinction. This expansion of plants' niche, however, requires a high enough rate of niche construction and a high enough initial plant biomass to fuel the positive ecological feedback between plants and their soil environment. On an evolutionary time scale, we consider that the rates of niche construction and nutrient uptake coevolve in plants while a trade-off constrains their values. Different evolutionary outcomes are possible depending on the shape of the trade-off. We show that niche construction results in an evolutionary feedback between plants and their soil environment such that plants partially regulate soil nutrient content. The direct benefit accruing to plants, however, plays a crucial role in the evolutionary advantage of niche construction.

  20. Neutral biogeography and the evolution of climatic niches.

    PubMed

    Boucher, Florian C; Thuiller, Wilfried; Davies, T Jonathan; Lavergne, Sébastien

    2014-05-01

    Recent debate on whether climatic niches are conserved through time has focused on how phylogenetic niche conservatism can be measured by deviations from a Brownian motion model of evolutionary change. However, there has been no evaluation of this methodological approach. In particular, the fact that climatic niches are usually obtained from distribution data and are thus heavily influenced by biogeographic factors has largely been overlooked. Our main objective here was to test whether patterns of climatic niche evolution that are frequently observed might arise from neutral dynamics rather than from adaptive scenarios. We developed a model inspired by neutral biodiversity theory, where individuals disperse, compete, and undergo speciation independently of climate. We then sampled the climatic niches of species according to their geographic position and showed that even when species evolve independently of climate, their niches can nonetheless exhibit evolutionary patterns strongly differing from Brownian motion. Indeed, climatic niche evolution is better captured by a model of punctuated evolution with constraints due to landscape boundaries, two features that are traditionally interpreted as evidence for selective processes acting on the niche. We therefore suggest that deviation from Brownian motion alone should not be used as evidence for phylogenetic niche conservatism but that information on phenotypic traits directly linked to physiology is required to demonstrate that climatic niches have been conserved through time.

  1. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche.

    PubMed

    Chang, Chiung-Ying; Pasolli, H Amalia; Giannopoulou, Eugenia G; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-03-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in

  2. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche.

    PubMed

    Chang, Chiung-Ying; Pasolli, H Amalia; Giannopoulou, Eugenia G; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-03-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in

  3. Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

    PubMed

    Possamai, Fernanda; dos Santos, Juliano; Walber, Thais; Marcon, Juliana C; dos Santos, Tiago Souza; Lino de Oliveira, Cilene

    2015-04-01

    Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent.

  4. Insulin and Target of rapamycin signaling orchestrate the development of ovarian niche-stem cell units in Drosophila.

    PubMed

    Gancz, Dana; Gilboa, Lilach

    2013-10-01

    Tissue-specific stem cells and their niches are organized into functional units that respond to external cues in order to maintain organ homeostasis. Insulin and Target of rapamycin (Tor) signaling mediate external cues that control adult niches and stem cells. Whether these pathways play a role in the establishment of niche-stem cell units during organogenesis has been little explored. We show that during larval development both Insulin-like receptor (InR) and Tor participate in the establishment of ovarian niches and germline stem cells (GSCs) in Drosophila melanogaster. Tor and InR are required cell-autonomously for the proliferation of precursors for both somatic niches and GSCs. These pathways also promote the formation of terminal filaments (part of the somatic niche). Significantly, InR, but not Tor, signaling non-autonomously promotes primordial germ cell (PGC) differentiation. Somatic attenuation of the pathway retards PGC differentiation, whereas its activation results in their precocious differentiation. We also show that InR-mediated PGC differentiation is independent of somatic ecdysone signaling, but that further differentiation into cysts requires an ecdysone input. These results demonstrate that Tor and InR signaling actively participate in the formation of ovarian niches and stem cells by affecting both cell numbers and differentiation. The dual influence of Tor and InR on both somatic cells and PGCs ensures that these two cell populations develop coordinately. Our work further identifies a novel step in the regulation of germ cell differentiation by demonstrating that following bag of marbles expression, cyst formation requires an additional hormonal input.

  5. The suture provides a niche for mesenchymal stem cells of craniofacial bones

    PubMed Central

    Zhao, Hu; Feng, Jifan; Ho, Thach-Vu; Grimes, Weston; Urata, Mark; Chai, Yang

    2015-01-01

    Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the major MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating these cells are an indispensible stem cell population. Twist1+/− mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair. PMID:25799059

  6. Evolutionary consequences of niche construction and their implications for ecology.

    PubMed

    Laland, K N; Odling-Smee, F J; Feldman, M W

    1999-08-31

    Organisms regularly modify local resource distributions, influencing both their ecosystems and the evolution of traits whose fitness depends on such alterable sources of natural selection in environments. We call these processes niche construction. We explore the evolutionary consequences of niche construction using a two-locus population genetic model, which extends earlier analyses by allowing resource distributions to be influenced both by niche construction and by independent processes of renewal and depletion. The analysis confirms that niche construction can be a potent evolutionary agent by generating selection that leads to the fixation of otherwise deleterious alleles, supporting stable polymorphisms where none are expected, eliminating what would otherwise be stable polymorphisms, and generating unusual evolutionary dynamics. Even small amounts of niche construction, or niche construction that only weakly affects resource dynamics, can significantly alter both ecological and evolutionary patterns.

  7. Localization of juxtacrine factor ephrin-B2 in pituitary stem/progenitor cell niches throughout life.

    PubMed

    Yoshida, Saishu; Kato, Takako; Higuchi, Masashi; Chen, Mo; Ueharu, Hiroki; Nishimura, Naoto; Kato, Yukio

    2015-03-01

    We have recently reported that Sox2-expressing pituitary stem/progenitor cells contact each other via a tight-junction protein CAR to form stem/progenitor cell niches in the marginal cell layer facing the lumen and in the clusters scattered in the parenchyma of the anterior lobe. However, the microenvironment of the niche for the maintenance of stem cell function in the pituitary remains obscure. In this study of pituitary stem/progenitor cell niches, we have attempted to identify the expression of juxtacrine factor ephrin and its receptor. We have found that ephrin-B2 is expressed in the pituitary throughout development but changes its localization pattern. Notably, in the adult pituitary, ephrin-B2 immuno-signals occur in SOX2-, E-cadherin-, and CAR-triple-positive stem/progenitor cells in the niches. Our data suggest that ephrin-B2 signaling has an important role in the formation of pituitary stem/progenitor cell niches and in pituitary organogenesis.

  8. Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats

    PubMed Central

    Williamson, D J; Shepheard, S L; Cook, D A; Hargreaves, R J; Hill, R G; Cumberbatch, M J

    2001-01-01

    Migraine headache is thought to be caused by a distension of meningeal blood vessels, the activation of trigeminal sensory neurones and the the development of a central sensitization within the trigeminal nucleus caudalis (TNC). It has been proposed that clinically effective 5-HT1B/1D agonists act peripherally to inhibit the release of calcitonin gene-related peptide (CGRP) and neurogenic dural vasodilation, and to attenuate nociceptive neurotransmission within the TNC. Since opioids are also effective anti-migraine agents the present studies investigated the role of opioids within the trigemino-vascular system in anaesthetised rats. Electrical stimulation of the dura mater evoked neurogenic dural vasodilation which was significantly inhibited by morphine (1 mg kg−1) the selective μ-opioid agonist DAGO (10 μg kg−1) and the mixed agonist/antagonist butorphanol (1 mg kg−1) but not by the κ- and δ-opioid agonists (±) U50488H (100 μg kg−1) and DPDPE (1 mg kg−1). Morphine had no effect on CGRP-evoked dural vasodilation. In electrophysiological studies morphine (1 – 10 mg kg−1) significantly attenuated brainstem neuronal activity in response to electrical stimulation of the dura by 65% at 10 mg kg−1. Morphine (3 mg kg−1) also inhibited the TNC neuronal sensitization following CGRP-evoked dilation. The present studies have demonstrated that opioids block the nociceptive neurotransmission within the trigeminal nucleus caudalis and in addition inhibit neurogenic dural vasodilation via an action on μ-opioid receptors located on trigeminal sensory fibres innervating dural blood vessels. These peripheral and central actions are similar to those of the ‘triptan' 5-HT1B/1D agonists and could account for the anti-migraine actions of opioids. PMID:11454653

  9. Furosemide modifies heart hypertrophy and glycosaminoglycan myocardium content in a rat model of neurogenic hypertension.

    PubMed

    Pourzitaki, Chryssa; Tsaousi, Georgia; Manthou, Maria Eleni; Karakiulakis, Georgios; Kouvelas, Dimitrios; Papakonstantinou, Eleni

    2016-08-01

    Hypertension is a major risk factor for atherogenesis and heart hypertrophy, both of which are associated with specific morphological and functional changes of the myocardium. Glycosaminoglycans (GAGs) are complex molecules involved both in tissue morphology and function. In the present study, we investigated the effects of neurogenic hypertension and subsequent antihypertensive treatment with furosemide, on heart hypertrophy and the content of GAGs in the myocardium. Neurogenic hypertension was achieved in male Wistar rats by bilateral aortic denervation (bAD). At days 2, 7 and 15 after surgery, animals were sacrificed and the hearts were dissected away, weighted, and homogenized. Total GAGs were assessed by measuring the uronic acid content colorimetrically and individual GAGs were isolated and characterized by enzymatic treatment, with GAG-degrading enzymes, using electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes. In bAD-animals blood pressure, blood pressure lability, heart rate and heart weight were significantly increased 15 days postoperatively. These effects were prevented by treatment with furosemide. Major GAGs identified in the heart were chondroitin sulphates, heparin (H), heparan sulphate (HS) and hyaluronic acid. The content of uronic and the relative content of H and HS in the heart in bAD animals significantly decreased from day 2 to day 15 postoperatively. Furosemide prevented the bAD induced decrease in GAG content. Considering that H and HS are potent inhibitors of cardiomyocyte hypertrophy, our results indicate that heart hypertrophy induced by neurogenic hypertension may be associated with decreases in the relative content of heparin and heparan sulphate in the heart. PMID:27221775

  10. Neurogenic bowel management after spinal cord injury: A systematic review of the evidence

    PubMed Central

    Krassioukov, Andrei; Eng, Janice J.; Claxton, Geri; Sakakibara, Brodie M.; Shum, Serena

    2011-01-01

    OBJECTIVE To systematically review evidence for the management of neurogenic bowel in individuals with spinal cord injuries (SCI). DATA SOURCES Literature searches were conducted for relevant articles, as well as practice guidelines, using numerous electronic databases. Manual searches of retrieved articles from 1950 to July 2009 were also conducted to identify literature. STUDY SELECTION Randomized controlled trials, prospective cohort, case-control, and pre-post studies, and case reports that assessed pharmacological and non-pharmacological intervention for the management of the neurogenic bowel in SCI were included. DATA EXTRACTION Two independent reviewers evaluated each study’s quality, using the PEDro scale for RCTs and the Downs & Black scale for all other studies. Results were tabulated and levels of evidence assigned. DATA SYNTHESIS 2956 studies were found as a result of the literature search. Upon review of the titles and abstracts, 52 studies met the inclusion criteria. Multi-faceted programs are the first approach to neurogenic bowel and are supported by lower levels of evidence. Of the non-pharmacological (conservative and non-surgical) interventions, transanal irrigation is a promising treatment to reduce constipation and fecal incontinence. When conservative management is not effective, pharmacological interventions (e.g., prokinetic agents) are supported by strong evidence for the treatment of chronic constipation. When conservative and pharmacological treatments are not effective, surgical interventions may be considered and are supported by lower levels of evidence in reducing complications. CONCLUSIONS Often, more than one procedure is necessary to develop an effective bowel routine. Evidence is low for non-pharmacological approaches and high for pharmacological interventions. PMID:20212501

  11. Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat.

    PubMed

    Costa, M; Dodds, K N; Wiklendt, L; Spencer, N J; Brookes, S J H; Dinning, P G

    2013-11-15

    Gastrointestinal motility involves interactions between myogenic and neurogenic processes intrinsic to the gut wall. We have compared the presence of propagating myogenic contractions of the isolated colon in four experimental animals (guinea pig, mouse, rabbit, and rat), following blockade of enteric neural activity. Isolated colonic preparations were distended with fluid, with the anal end either closed or open. Spatiotemporal maps of changes in diameter were constructed from video recordings. Distension-induced peristaltic contractions were abolished by tetrodotoxin (TTX; 0.6 μM) in all animal species. Subsequent addition of carbachol (0.1-1 μM) did not evoke myogenic motor patterns in the mouse or guinea pig, although some activity was observed in rabbit and rat colon. These myogenic contractions propagated both orally and anally and differed from neurogenic propagating contractions in their frequency, extent of propagation, and polarity. Niflumic acid (300 μM), used to block myogenic activity, also blocked neural peristalsis and thus cannot be used to discriminate between these mechanisms. In all species, except the mouse colon, small myogenic "ripple" contractions were revealed in TTX, but in both rat and rabbit an additional, higher-frequency ripple-type contraction was superimposed. Following blockade of enteric nerve function, a muscarinic agonist can evoke propulsive myogenic peristaltic contractions in isolated rabbit and rat colon, but not in guinea pig or mouse colon. Marked differences between species exist in the ability of myogenic mechanisms to propel luminal content, but in all species there is normally a complex interplay between neurogenic and myogenic processes.

  12. Quantifiable diagnosis of muscular dystrophies and neurogenic atrophies through network analysis

    PubMed Central

    2013-01-01

    Background The diagnosis of neuromuscular diseases is strongly based on the histological characterization of muscle biopsies. However, this morphological analysis is mostly a subjective process and difficult to quantify. We have tested if network science can provide a novel framework to extract useful information from muscle biopsies, developing a novel method that analyzes muscle samples in an objective, automated, fast and precise manner. Methods Our database consisted of 102 muscle biopsy images from 70 individuals (including controls, patients with neurogenic atrophies and patients with muscular dystrophies). We used this to develop a new method, Neuromuscular DIseases Computerized Image Analysis (NDICIA), that uses network science analysis to capture the defining signature of muscle biopsy images. NDICIA characterizes muscle tissues by representing each image as a network, with fibers serving as nodes and fiber contacts as links. Results After a ‘training’ phase with control and pathological biopsies, NDICIA was able to quantify the degree of pathology of each sample. We validated our method by comparing NDICIA quantification of the severity of muscular dystrophies with a pathologist’s evaluation of the degree of pathology, resulting in a strong correlation (R = 0.900, P <0.00001). Importantly, our approach can be used to quantify new images without the need for prior ‘training’. Therefore, we show that network science analysis captures the useful information contained in muscle biopsies, helping the diagnosis of muscular dystrophies and neurogenic atrophies. Conclusions Our novel network analysis approach will serve as a valuable tool for assessing the etiology of muscular dystrophies or neurogenic atrophies, and has the potential to quantify treatment outcomes in preclinical and clinical trials. PMID:23514382

  13. A mathematical model of salt-sensitive hypertension: the neurogenic hypothesis.

    PubMed

    Averina, Viktoria A; Othmer, Hans G; Fink, Gregory D; Osborn, John W

    2014-09-12

    Salt sensitivity of arterial pressure (salt-sensitive hypertension) is a serious global health issue. The causes of salt-sensitive hypertension are extremely complex and mathematical models can elucidate potential mechanisms that are experimentally inaccessible. Until recently, the only mathematical model for long-term control of arterial pressure was the model of Guyton and Coleman; referred to as the G-C model. The core of this model is the assumption that sodium excretion is driven by renal perfusion pressure, the so-called 'renal function curve'. Thus, the G-C model dictates that all forms of hypertension are due to a primary shift of the renal function curve to a higher operating pressure. However, several recent experimental studies in a model of hypertension produced by the combination of a high salt intake and administration of angiotensin II, the AngII-salt model, are inconsistent with the G-C model. We developed a new mathematical model that does not limit the cause of salt-sensitive hypertension solely to primary renal dysfunction. The model is the first known mathematical counterexample to the assumption that all salt-sensitive forms of hypertension require a primary shift of renal function: we show that in at least one salt-sensitive form of hypertension the requirement is not necessary. We will refer to this computational model as the 'neurogenic model'. In this Symposium Review we discuss how, despite fundamental differences between the G-C model and the neurogenic model regarding mechanisms regulating sodium excretion and vascular resistance, they generate similar haemodynamic profiles of AngII-salt hypertension. In addition, the steady-state relationships between arterial pressure and sodium excretion, a correlation that is often erroneously presented as the 'renal function curve', are also similar in both models. Our findings suggest that salt-sensitive hypertension is not due solely to renal dysfunction, as predicted by the G-C model, but may

  14. A mathematical model of salt-sensitive hypertension: the neurogenic hypothesis.

    PubMed

    Averina, Viktoria A; Othmer, Hans G; Fink, Gregory D; Osborn, John W

    2015-07-15

    Salt sensitivity of arterial pressure (salt-sensitive hypertension) is a serious global health issue. The causes of salt-sensitive hypertension are extremely complex and mathematical models can elucidate potential mechanisms that are experimentally inaccessible. Until recently, the only mathematical model for long-term control of arterial pressure was the model of Guyton and Coleman; referred to as the G-C model. The core of this model is the assumption that sodium excretion is driven by renal perfusion pressure, the so-called 'renal function curve'. Thus, the G-C model dictates that all forms of hypertension are due to a primary shift of the renal function curve to a higher operating pressure. However, several recent experimental studies in a model of hypertension produced by the combination of a high salt intake and administration of angiotensin II, the AngII-salt model, are inconsistent with the G-C model. We developed a new mathematical model that does not limit the cause of salt-sensitive hypertension solely to primary renal dysfunction. The model is the first known mathematical counterexample to the assumption that all salt-sensitive forms of hypertension require a primary shift of renal function: we show that in at least one salt-sensitive form of hypertension the requirement is not necessary. We will refer to this computational model as the 'neurogenic model'. In this Symposium Review we discuss how, despite fundamental differences between the G-C model and the neurogenic model regarding mechanisms regulating sodium excretion and vascular resistance, they generate similar haemodynamic profiles of AngII-salt hypertension. In addition, the steady-state relationships between arterial pressure and sodium excretion, a correlation that is often erroneously presented as the 'renal function curve', are also similar in both models. Our findings suggest that salt-sensitive hypertension is not due solely to renal dysfunction, as predicted by the G-C model, but may

  15. Development and molecular composition of the hepatic progenitor cell niche.

    PubMed

    Vestentoft, Peter Siig

    2013-05-01

    End-stage liver diseases represent major health problems that are currently treated by liver transplantation. However, given the world-wide shortage of donor livers novel strategies are needed for therapeutic treatment. Adult stem cells have the ability to self-renew and differentiate into the more specialized cell types of a given organ and are found in tissues throughout the body. These cells, whose progeny are termed progenitor cells in human liver and oval cells in rodents, have the potential to treat patients through the generation of hepatic parenchymal cells, even from the patient's own tissue. Little is known regarding the nature of the hepatic progenitor cells. Though they are suggested to reside in the most distal part of the biliary tree, the canal of Hering, the lack of unique surface markers for these cells has hindered their isolation and characterization. Upon activation, they proliferate and form ductular structures, termed "ductular reactions", which radiate into the hepatic parenchyma. The ductular reactions contain activated progenitor cells that not only acquire a phenotype resembling that observed in developing liver but also display markers of differentiation shared with the cholangiocytic or hepatocytic lineages, the two parenchymal hepatic cell types. Interactions between the putative progenitor cells, the surrounding support cells and the extracellular matrix scaffold, all constituting the progenitor cell niche, are likely to be important for regulating progenitor cell activity and differentiation. Therefore, identifying novel progenitor cell markers and deciphering their microenvironment could facilitate clinical use. The aims of the present PhD thesis were to expand knowledge of the hepatic progenitor cell niche and characterize it both during development and in disease. Several animal models of hepatic injury are known to induce activation of the progenitor cells. In order to identify possible progenitor cell markers and niche components

  16. [Caring for children with neurogenic bladder dysfunction: social representation of these children's and their mothers' needs].

    PubMed

    Furlan, Maria de Fátima Farinha Martins; Ferriani, Maria das Graças Carvalho; Gomes, Romeu

    2003-01-01

    The purpose of this study was to know and analyze the representations and needs of school-age children with neurogenic bladder dysfunction and of their mothers. This is a qualitative study; whose methodology was based on social representations. According to the interposition of empirical end analytical categories, the living and caring are respectively represented by mothers as "a problem" and "all me"; the children, in turn, interpret the differentiated and prejudiced interaction they suffer in the setting they live in as "it is not fair".

  17. Transient Receptor Potential Ankyrin 1 (TRPA1) Channel and Neurogenic Inflammation in Pathogenesis of Asthma

    PubMed Central

    Yang, Hang; Li, ShuZhuang

    2016-01-01

    Asthma is characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR), and it affects 300 million people worldwide. However, our current understanding of the molecular mechanisms that underlie asthma remains limited. Recent studies have suggested that transient receptor potential ankyrin 1 (TRPA1), one of the transient receptor potential cation channels, may be involved in airway inflammation in asthma. The present review discusses the relationship between TRPA1 and neurogenic inflammation in asthma, hoping to enhance our understanding of the mechanisms of airway inflammation in asthma. PMID:27539812

  18. Aphasia, apraxia and neurogenic stuttering as complications of metrizamide myelography (speech deficits following myelography).

    PubMed

    Pimental, P A; Gorelick, P B

    1985-11-01

    Aphasia following metrizamide myelography has been reported infrequently. During a seven-month period, we examined two patients who developed Broca's aphasia, apraxia of speech, oral-buccal-facial apraxia and neurogenic stuttering after intrathecal metrizamide administration. In each case, focal neurologic deficits were accompanied by clinical, electroencephalographic and radiologic signs of generalized neurologic disease. Serial speech and language evaluations initially revealed severe deficits that were largely resolved by the third day post-myelography. Out-patient follow-up examinations demonstrated persistence of mild speech and language abnormalities in each case. Our findings suggest that metrizamide may cause longlasting neurologic dysfunction. PMID:4082914

  19. Back Pain, Neurogenic Symptoms, and Physical Function in Relation to Spondylolisthesis among Elderly Men

    PubMed Central

    Denard, Patrick J.; Holton, Kathleen F.; Miller, Jessica; Fink, Howard A.; Kado, Deborah M.; Marshall, Lynn M.; Yoo, Jung U.

    2010-01-01

    Background Context Degenerative spondylolisthesis is a presumed cause of back pain. Previous studies of spondylolisthesis and back pain included only women or combined results for men and women. Comparisons of the frequency of back pain, neurogenic symptoms, and functional limitations specifically among elderly men with and without spondylolisthesis are needed. Purpose To determine associations of prevalent spondylolisthesis with back pain symptoms, neurogenic symptoms, and functional limitations among elderly men. Study Design/ Setting: Cross-sectional epidemiologic study conducted within the Osteoporotic Fractures in Men (MrOS) cohort. The MrOS cohort is comprised of 5,995 community dwelling men ages ≥65 years who were recruited at 6 US academic medical centers. Extensive self-reported data and lumbar spine radiographs were obtained for all MrOS participants at baseline. Patient Sample For this study, 300 men were selected at random specifically for the evaluation of spondylolisthesis on the baseline spine radiographs. Outcome Measures Standardized questionnaires were used to assess self-reported back pain, leg pain (radiculopathy), lower extremity numbness (paresthesias) and lower extremity weakness occurring in the past 12 months, and to ascertain current difficulty with activities of daily living. Methods In the present study, radiographic spondylolisthesis was classified as forward slip of ≥5%. Prevalence of back pain, neurogenic symptoms and difficulty with activities of daily living were compared between men with and without spondylolisthesis using chisquare or Fisher’s exact tests. Results Spondylolisthesis was present among 92 (31%) men. Among men with and without spondylolisthesis, back pain (63% vs. 67%, p=0.46) and moderate/severe back pain (41% vs. 38%, p=0.76) were reported with similar frequency. Men with spondylolisthesis more often reported radiculopathy (33% vs. 22%, p=0.06), paresthesias (18% vs. 11%, p= 0.10) and weakness (18% vs. 9%, p=0

  20. How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

    PubMed Central

    Baron, Maximilien; Grise, Philippe; Cornu, Jean-Nicolas

    2016-01-01

    Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review. PMID:26981445

  1. The novel anti-migraine agent rizatriptan inhibits neurogenic dural vasodilation and extravasation.

    PubMed

    Williamson, D J; Shepheard, S L; Hill, R G; Hargreaves, R J

    1997-06-01

    These studies in anaesthetised rats showed, using intravital microscopy, that the novel anti-migraine agent, rizatriptan, significantly reduced electrically stimulated dural vasodilation but had no effect on increases in dural vessel diameter produced by exogenous substance P or calcitonin gene-related peptide (CGRP). Rizatriptan also significantly inhibited dural plasma protein extravasation produced by high intensity electrical stimulation of the trigeminal ganglion. We suggest that rizatriptan inhibits the release of sensory neuropeptides from perivascular trigeminal nerves to prevent neurogenic vasodilation and extravasation in the dura mater. These prejunctional inhibitory effects may be involved in the anti-migraine action of rizatriptan. PMID:9203569

  2. Transient Receptor Potential Ankyrin 1 (TRPA1) Channel and Neurogenic Inflammation in Pathogenesis of Asthma.

    PubMed

    Yang, Hang; Li, ShuZhuang

    2016-01-01

    Asthma is characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR), and it affects 300 million people worldwide. However, our current understanding of the molecular mechanisms that underlie asthma remains limited. Recent studies have suggested that transient receptor potential ankyrin 1 (TRPA1), one of the transient receptor potential cation channels, may be involved in airway inflammation in asthma. The present review discusses the relationship between TRPA1 and neurogenic inflammation in asthma, hoping to enhance our understanding of the mechanisms of airway inflammation in asthma. PMID:27539812

  3. Neurogenic benign fasciculations, pseudomyotonia, and pseudotetany. A disease in search of a name.

    PubMed

    Coërs, C; Telerman-Toppet, N; Durdu, J

    1981-05-01

    We studied two patients with abnormal spontaneous muscular activity. The first had widespread fasciculations, painful spasms, delayed muscular relaxation, and hyperhidrosis. Improvement occurred after several years. The second case had generalized paresthesia, mild stiffness, a positive result from Trusseau's test, and was relieved by administration of carbamazepine. Both patients had abnormal conduction velocity. Examination of muscle biopsy specimens disclosed fiber type grouping and increased collateral ramification of motor axons. These observations exemplify symptoms and signs that resemble those of myotonia and tetany and occasionally occur in partial denervation. they provide additional evidence of the neurogenic nature of Isaacs-Mertens syndrome. PMID:7224912

  4. Remote Sensing of Niches for Thermotropic Life.

    NASA Astrophysics Data System (ADS)

    Muller, A. W.

    2002-12-01

    The recognized biological energy sources are light and food. Mechanical systems can gain free energy from heat using a temperature difference or thermal cycling. Imagine that biological systems could also live on heat. Call the process `thermosynthesis' and let it occur in a thermal gradient or convection cell. Many candidate niches for thermosynthesizers then exist. Temperature differences are present across many interfaces: soil/air, rock/air, natural water (ocean, lake, river)/air, ice (also snow)/air, soil/snow, water (ocean,lake)/surface-ice. Within natural waters large temperature gradients are found; thermoclines separate the warm surface from the cold deep. Convection occurs in hot springs, in many other natural waters, and in the Earth's atmosphere. On Earth, organism presence is conspicuous in all these candidate niches. The Solar System contains many candidate niches as well. They should be detectable by IR methods. They can be categorized in five types: (1) Convection. Convecting oceans (Mars and Venus in the past) or atmospheres (Venus, Big Outer Planets). (2) Convecting Aquifer (Mars). (3) Surface-Ice Cover. Some of the Moons of the Outer Planets. (4) Shaded Crater Iterior. The poles of Mercury and The Moon. (5) Spinners. Small objects rotating in the sunlight: ice-covered meteorites, asteroids, comets. They could transport thermosynthesizers within the Solar System. How plausible is thermosynthesis? It can be shown that thermosynthesis (1) could be effected using parts of the contemporary photosynthetic machinery, and (2) may have supported early evolution. The standard biological energy carrier, ATP, would be synthesized during thermal cycling of a progenitor of the F1 moiety of the contemporary ATPsynthase enzyme; this progenitor is thermally folded/unfolded during the cycle. Contemporary ATPsynthase works according to the `binding change mechanism': substrates are bound in a local, dehydrated enzymatic cleft, where they condense to form a bound

  5. Multipotent neurogenic fate of mesenchymal stem cell is determined by Cdk4-mediated hypophosphorylation of Smad-STAT3.

    PubMed

    Kim, Dong-Young; Lee, Janet; Kang, Dongrim; Lee, Do-Hyeong; Kim, Yoon-Ja; Hwang, Sang-Gu; Kim, Dong-Ik; Lee, Chang-Woo; Lee, Kyung-Hoon

    2016-07-01

    Cyclin-dependent kinase (Cdk) in complex with a corresponding cyclin plays a pivotal role in neurogenic differentiation. In particular, Cdk4 activity acts as a signaling switch to direct human mesenchymal stem cells (MSCs) to neural transdifferentiation. However, the molecular evidence of how Cdk4 activity converts MSCs to neurogenic lineage remains unknown. Here, we found that Cdk4 inhibition in human MSCs enriches the populations of neural stem and progenitor pools rather than differentiated glial and neuronal cell pools. Interestingly, Cdk4 inhibition directly inactivates Smads and subsequently STAT3 signaling by hypophosphorylation, and both Cdk4 and Smads levels are linked during the processes of neural transdifferentiation and differentiation. In summary, our results provide novel molecular evidence in which Cdk4 inhibition leads to directing human MSCs to a multipotent neurogenic fate by inactivating Smads-STAT3 signaling. PMID:27192561

  6. Ecological niche transferability using invasive species as a case study.

    PubMed

    Fernández, Miguel; Hamilton, Healy

    2015-01-01

    Species distribution modeling is widely applied to predict invasive species distributions and species range shifts under climate change. Accurate predictions depend upon meeting the assumption that ecological niches are conserved, i.e., spatially or temporally transferable. Here we present a multi-taxon comparative analysis of niche conservatism using biological invasion events well documented in natural history museum collections. Our goal is to assess spatial transferability of the climatic niche of a range of noxious terrestrial invasive species using two complementary approaches. First we compare species' native versus invasive ranges in environmental space using two distinct methods, Principal Components Analysis and Mahalanobis distance. Second we compare species' native versus invaded ranges in geographic space as estimated using the species distribution modeling technique Maxent and the comparative index Hellinger's I. We find that species exhibit a range of responses, from almost complete transferability, in which the invaded niches completely overlap with the native niches, to a complete dissociation between native and invaded ranges. Intermediate responses included expansion of dimension attributable to either temperature or precipitation derived variables, as well as niche expansion in multiple dimensions. We conclude that the ecological niche in the native range is generally a poor predictor of invaded range and, by analogy, the ecological niche may be a poor predictor of range shifts under climate change. We suggest that assessing dimensions of niche transferability prior to standard species distribution modeling may improve the understanding of species' dynamics in the invaded range.

  7. Evolution of climatic niche specialization: a phylogenetic analysis in amphibians.

    PubMed

    Bonetti, Maria Fernanda; Wiens, John J

    2014-11-22

    The evolution of climatic niche specialization has important implications for many topics in ecology, evolution and conservation. The climatic niche reflects the set of temperature and precipitation conditions where a species can occur. Thus, specialization to a limited set of climatic conditions can be important for understanding patterns of biogeography, species richness, community structure, allopatric speciation, spread of invasive species and responses to climate change. Nevertheless, the factors that determine climatic niche width (level of specialization) remain poorly explored. Here, we test whether species that occur in more extreme climates are more highly specialized for those conditions, and whether there are trade-offs between niche widths on different climatic niche axes (e.g. do species that tolerate a broad range of temperatures tolerate only a limited range of precipitation regimes?). We test these hypotheses in amphibians, using phylogenetic comparative methods and global-scale datasets, including 2712 species with both climatic and phylogenetic data. Our results do not support either hypothesis. Rather than finding narrower niches in more extreme environments, niches tend to be narrower on one end of a climatic gradient but wider on the other. We also find that temperature and precipitation niche breadths are positively related, rather than showing trade-offs. Finally, our results suggest that most amphibian species occur in relatively warm and dry environments and have relatively narrow climatic niche widths on both of these axes. Thus, they may be especially imperilled by anthropogenic climate change.

  8. Evolution of climatic niche specialization: a phylogenetic analysis in amphibians

    PubMed Central

    Bonetti, Maria Fernanda; Wiens, John J.

    2014-01-01

    The evolution of climatic niche specialization has important implications for many topics in ecology, evolution and conservation. The climatic niche reflects the set of temperature and precipitation conditions where a species can occur. Thus, specialization to a limited set of climatic conditions can be important for understanding patterns of biogeography, species richness, community structure, allopatric speciation, spread of invasive species and responses to climate change. Nevertheless, the factors that determine climatic niche width (level of specialization) remain poorly explored. Here, we test whether species that occur in more extreme climates are more highly specialized for those conditions, and whether there are trade-offs between niche widths on different climatic niche axes (e.g. do species that tolerate a broad range of temperatures tolerate only a limited range of precipitation regimes?). We test these hypotheses in amphibians, using phylogenetic comparative methods and global-scale datasets, including 2712 species with both climatic and phylogenetic data. Our results do not support either hypothesis. Rather than finding narrower niches in more extreme environments, niches tend to be narrower on one end of a climatic gradient but wider on the other. We also find that temperature and precipitation niche breadths are positively related, rather than showing trade-offs. Finally, our results suggest that most amphibian species occur in relatively warm and dry environments and have relatively narrow climatic niche widths on both of these axes. Thus, they may be especially imperilled by anthropogenic climate change. PMID:25274369

  9. Evolution of climatic niche specialization: a phylogenetic analysis in amphibians.

    PubMed

    Bonetti, Maria Fernanda; Wiens, John J

    2014-11-22

    The evolution of climatic niche specialization has important implications for many topics in ecology, evolution and conservation. The climatic niche reflects the set of temperature and precipitation conditions where a species can occur. Thus, specialization to a limited set of climatic conditions can be important for understanding patterns of biogeography, species richness, community structure, allopatric speciation, spread of invasive species and responses to climate change. Nevertheless, the factors that determine climatic niche width (level of specialization) remain poorly explored. Here, we test whether species that occur in more extreme climates are more highly specialized for those conditions, and whether there are trade-offs between niche widths on different climatic niche axes (e.g. do species that tolerate a broad range of temperatures tolerate only a limited range of precipitation regimes?). We test these hypotheses in amphibians, using phylogenetic comparative methods and global-scale datasets, including 2712 species with both climatic and phylogenetic data. Our results do not support either hypothesis. Rather than finding narrower niches in more extreme environments, niches tend to be narrower on one end of a climatic gradient but wider on the other. We also find that temperature and precipitation niche breadths are positively related, rather than showing trade-offs. Finally, our results suggest that most amphibian species occur in relatively warm and dry environments and have relatively narrow climatic niche widths on both of these axes. Thus, they may be especially imperilled by anthropogenic climate change. PMID:25274369

  10. Foraging and farming as niche construction: stable and unstable adaptations.

    PubMed

    Rowley-Conwy, Peter; Layton, Robert

    2011-03-27

    All forager (or hunter-gatherer) societies construct niches, many of them actively by the concentration of wild plants into useful stands, small-scale cultivation, burning of natural vegetation to encourage useful species, and various forms of hunting, collectively termed 'low-level food production'. Many such niches are stable and can continue indefinitely, because forager populations are usually stable. Some are unstable, but these usually transform into other foraging niches, not geographically expansive farming niches. The Epipalaeolithic (final hunter-gatherer) niche in the Near East was complex but stable, with a relatively high population density, until destabilized by an abrupt climatic change. The niche was unintentionally transformed into an agricultural one, due to chance genetic and behavioural attributes of some wild plant and animal species. The agricultural niche could be exported with modifications over much of the Old World. This was driven by massive population increase and had huge impacts on local people, animals and plants wherever the farming niche was carried. Farming niches in some areas may temporarily come close to stability, but the history of the last 11,000 years does not suggest that agriculture is an effective strategy for achieving demographic and political stability in the world's farming populations.

  11. Ecological Niche Transferability Using Invasive Species as a Case Study

    PubMed Central

    Fernández, Miguel; Hamilton, Healy

    2015-01-01

    Species distribution modeling is widely applied to predict invasive species distributions and species range shifts under climate change. Accurate predictions depend upon meeting the assumption that ecological niches are conserved, i.e., spatially or temporally transferable. Here we present a multi-taxon comparative analysis of niche conservatism using biological invasion events well documented in natural history museum collections. Our goal is to assess spatial transferability of the climatic niche of a range of noxious terrestrial invasive species using two complementary approaches. First we compare species’ native versus invasive ranges in environmental space using two distinct methods, Principal Components Analysis and Mahalanobis distance. Second we compare species’ native versus invaded ranges in geographic space as estimated using the species distribution modeling technique Maxent and the comparative index Hellinger’s I. We find that species exhibit a range of responses, from almost complete transferability, in which the invaded niches completely overlap with the native niches, to a complete dissociation between native and invaded ranges. Intermediate responses included expansion of dimension attributable to either temperature or precipitation derived variables, as well as niche expansion in multiple dimensions. We conclude that the ecological niche in the native range is generally a poor predictor of invaded range and, by analogy, the ecological niche may be a poor predictor of range shifts under climate change. We suggest that assessing dimensions of niche transferability prior to standard species distribution modeling may improve the understanding of species’ dynamics in the invaded range. PMID:25785858

  12. Foraging and farming as niche construction: stable and unstable adaptations

    PubMed Central

    Rowley-Conwy, Peter; Layton, Robert

    2011-01-01

    All forager (or hunter–gatherer) societies construct niches, many of them actively by the concentration of wild plants into useful stands, small-scale cultivation, burning of natural vegetation to encourage useful species, and various forms of hunting, collectively termed ‘low-level food production’. Many such niches are stable and can continue indefinitely, because forager populations are usually stable. Some are unstable, but these usually transform into other foraging niches, not geographically expansive farming niches. The Epipalaeolithic (final hunter–gatherer) niche in the Near East was complex but stable, with a relatively high population density, until destabilized by an abrupt climatic change. The niche was unintentionally transformed into an agricultural one, due to chance genetic and behavioural attributes of some wild plant and animal species. The agricultural niche could be exported with modifications over much of the Old World. This was driven by massive population increase and had huge impacts on local people, animals and plants wherever the farming niche was carried. Farming niches in some areas may temporarily come close to stability, but the history of the last 11 000 years does not suggest that agriculture is an effective strategy for achieving demographic and political stability in the world's farming populations. PMID:21320899

  13. Symbiosis catalyses niche expansion and diversification

    PubMed Central

    Joy, Jeffrey B.

    2013-01-01

    Interactions between species are important catalysts of the evolutionary processes that generate the remarkable diversity of life. Symbioses, conspicuous and inherently interesting forms of species interaction, are pervasive throughout the tree of life. However, nearly all studies of the impact of species interactions on diversification have concentrated on competition and predation leaving unclear the importance of symbiotic interaction. Here, I show that, as predicted by evolutionary theories of symbiosis and diversification, multiple origins of a key innovation, symbiosis between gall-inducing insects and fungi, catalysed both expansion in resource use (niche expansion) and diversification. Symbiotic lineages have undergone a more than sevenfold expansion in the range of host-plant taxa they use relative to lineages without such fungal symbionts, as defined by the genetic distance between host plants. Furthermore, symbiotic gall-inducing insects are more than 17 times as diverse as their non-symbiotic relatives. These results demonstrate that the evolution of symbiotic interaction leads to niche expansion, which in turn catalyses diversification. PMID:23390106

  14. A stem cell niche dominance theorem

    PubMed Central

    2011-01-01

    Background Multilevelness is a defining characteristic of complex systems. For example, in the intestinal tissue the epithelial lining is organized into crypts that are maintained by a niche of stem cells. The behavior of the system 'as a whole' is considered to emerge from the functioning and interactions of its parts. What we are seeking here is a conceptual framework to demonstrate how the "fate" of intestinal crypts is an emergent property that inherently arises from the complex yet robust underlying biology of stem cells. Results We establish a conceptual framework in which to formalize cross-level principles in the context of tissue organization. To this end we provide a definition for stemness, which is the propensity of a cell lineage to contribute to a tissue fate. We do not consider stemness a property of a cell but link it to the process in which a cell lineage contributes towards tissue (mal)function. We furthermore show that the only logically feasible relationship between the stemness of cell lineages and the emergent fate of their tissue, which satisfies the given criteria, is one of dominance from a particular lineage. Conclusions The dominance theorem, conceived and proven in this paper, provides support for the concepts of niche succession and monoclonal conversion in intestinal crypts as bottom-up relations, while crypt fission is postulated to be a top-down principle. PMID:21214945

  15. Neisserial Molecular Adaptations to the Nasopharyngeal Niche.

    PubMed

    Laver, Jay R; Hughes, Sara E; Read, Robert C

    2015-01-01

    The exclusive reservoir of the genus Neisseria is the human. Of the broad range of species that comprise the Neisseria, only two are frequently pathogenic, and only one of those is a resident of the nasopharynx. Although Neisseria meningitidis can cause severe disease if it invades the bloodstream, the vast majority of interactions between humans and Neisseria are benign, with the bacteria inhabiting its mucosal niche as a non-invasive commensal. Understandably, with the exception of Neisseria gonorrhoeae, which preferentially colonises the urogenital tract, the neisseriae are extremely well adapted to survival in the human nasopharynx, their sole biological niche. The purpose of this review is to provide an overview of the molecular mechanisms evolved by Neisseria to facilitate colonisation and survival within the nasopharynx, focussing on N. meningitidis. The organism has adapted to survive in aerosolised transmission and to attach to mucosal surfaces. It then has to replicate in a nutrition-poor environment and resist immune and competitive pressure within a polymicrobial complex. Temperature and relative gas concentrations (nitric oxide and oxygen) are likely to be potent initial signals of arrival within the nasopharyngeal environment, and this review will focus on how N. meningitidis responds to these to increase the likelihood of its survival. PMID:26210107

  16. The perivascular niche regulates breast tumor dormancy

    PubMed Central

    Peinado, Héctor; Mori, Hidetoshi; Matei, Irina R.; Evason, Kimberley J.; Brazier, Hélène; Almeida, Dena; Koller, Antonius; Hajjar, Katherine A.; Stainier, Didier Y.R.; Chen, Emily I.; Lyden, David

    2013-01-01

    In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumor cells (DTCs) are kept dormant, and what ‘wakes them up’, are fundamental problems in tumor biology. To address these questions, we utilized metastasis assays in mice to show that dormant DTCs reside upon microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumor-promoting, endothelial tip cell-derived factors. Our work reveals that stable microvasculature constitutes a ‘dormant niche,’ whereas sprouting neovasculature sparks micrometastatic outgrowth. PMID:23728425

  17. Updating stored memory requires adult hippocampal neurogenesis.

    PubMed

    Suárez-Pereira, Irene; Carrión, Ángel M

    2015-09-11

    Adult hippocampal neurogenesis appears to influence hippocampal functions, such as memory formation for example. While adult hippocampal neurogenesis is known to be involved in hippocampal-dependent learning and consolidation processes, the role of such immature neurons in memory reconsolidation, a process involved in the modification of stored memories, remains unclear. Here, using a novel fast X-ray ablation protocol to deplete neurogenic cells, we have found that adult hippocampal neurogenesis is required to update object recognition stored memory more than to reinforce it. Indeed, we show that immature neurons were selectively recruited to hippocampal circuits during the updating of stored information. Thus, our data demonstrate a new role for neurogenesis in cognitive processes, adult hippocampal neurogenesis being required for the updating of stored OR memories. These findings suggest that manipulating adult neurogenesis may have a therapeutic application in conditions associated with traumatic stored memory, for example.

  18. Updating stored memory requires adult hippocampal neurogenesis

    PubMed Central

    Suárez-Pereira, Irene; Carrión, Ángel M

    2015-01-01

    Adult hippocampal neurogenesis appears to influence hippocampal functions, such as memory formation for example. While adult hippocampal neurogenesis is known to be involved in hippocampal-dependent learning and consolidation processes, the role of such immature neurons in memory reconsolidation, a process involved in the modification of stored memories, remains unclear. Here, using a novel fast X-ray ablation protocol to deplete neurogenic cells, we have found that adult hippocampal neurogenesis is required to update object recognition stored memory more than to reinforce it. Indeed, we show that immature neurons were selectively recruited to hippocampal circuits during the updating of stored information. Thus, our data demonstrate a new role for neurogenesis in cognitive processes, adult hippocampal neurogenesis being required for the updating of stored OR memories. These findings suggest that manipulating adult neurogenesis may have a therapeutic application in conditions associated with traumatic stored memory, for example. PMID:26358557

  19. Effects and Safety of Aqueous Extract of Poncirus fructus in Spinal Cord Injury with Neurogenic Bowel

    PubMed Central

    Kim, Ji Hee; Lee, Su Kyung

    2016-01-01

    Objective. To investigate the effects and safety of the aqueous extract of the dried, immature fruit of Poncirus trifoliata (L.) Raf., known as Poncirus fructus (PF), in spinal cord injury (SCI) patients with neurogenic bowel. Methods. Thirty-one SCI patients with neurogenic bowel were recruited. Patients were evaluated based on clinical information, constipation score, Bristol Stool Form Scale, stool retention score using plain abdominal radiograph, and colon transit time. PF was administered in dosages of 800 mg each prior to breakfast and lunch for 14 days. Results. The morphological feature of the stool before and after administration indicated a statistically significant difference from 3.52 ± 1.33 to 4.32 ± 1.44 points (p < 0.05). Stool retention score before and after administration of PF was represented with low significance (7.25 ± 1.60 to 6.46 ± 1.53 points) in the whole colon (p < 0.05), and the colon transit time was significantly shortened (57.41 ± 20.7 to 41.2 ± 25.5 hours) in terms of the whole transit time (p < 0.05). Side effects were observed in 7 people (28.0%) consisting of 2 people with soft stools and 5 people with diarrhea. Conclusion. For SCI patients, PF administration significantly improved defecation patterns, defecation retention, and colon transit time. PF could be an effective aid to improve colonic motility and constipation. PMID:27738444

  20. Electrically evoked neuropeptide release and neurogenic inflammation differ between rat and human skin

    PubMed Central

    Sauerstein, Katja; Klede, Monika; Hilliges, Marita; Schmelz, Martin

    2000-01-01

    Protein extravasation and vasodilatation can be induced by neuropeptides released from nociceptive afferents (neurogenic inflammation). We measured electrically evoked neuropeptide release and concomitant protein extravasation in human and rat skin using intradermal microdialysis. Plasmapheresis capillaries were inserted intradermally at a length of 1.5 cm in the volar forearm of human subjects or abdominal skin of rats. Capillaries were perfused with Ringer solution at a flow rate of 2.5 or 1.6 μl min−1. After a baseline period of 60 min capillaries were stimulated electrically (1 Hz, 80 mA, 0.5 ms or 4 Hz, 30 mA, 0.5 ms) for 30 min using a surface electrode directly above the capillaries and a stainless-steel wire inserted in the capillaries. Total protein concentration was assessed photometrically and calcitonin gene-related peptide (CGRP) and substance P (SP) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). In rat skin, electrical stimulation increased CGRP and total protein concentration in the dialysate. SP measurements showed a larger variance but only for the 1 Hz stimulation was the increased release significant. In human skin, electrical stimulation provoked a large flare reaction and at a frequency of 4 Hz both CGRP and SP concentrations increased significantly. In spite of the large flare reactions no protein extravasation was induced, which suggests major species differences. It will be of interest to investigate whether the lack of neurogenic protein extravasation is also valid under pathophysiological conditions. PMID:11118507

  1. Microneedle Electrode Array for Electrical Impedance Myography to Characterize Neurogenic Myopathy.

    PubMed

    Li, Zhao; Li, Yi; Liu, Mingsheng; Cui, Liying; Yu, Yude

    2016-05-01

    Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular assessment, wherein a low-intensity alternating current is applied to a muscle, and the consequent surface voltage patterns are evaluated. Commercial wet electrodes are most commonly used for EIM. However, these electrodes are not suitable for use on small muscles, as they do not effectively solve the problem of high electrode-skin contact impedance (ESCI) that negatively influences the quality of recorded biopotentials. To address this problem, we fabricated a novel microneedle electrode array (MEA) that consists of 124-µm-long microneedles. Compared to wet electrodes, the MEA could pierce through the outer skin surface in a painless and micro-invasive manner, and could thus effectively reduce ESCI. The MEA has excellent test-retest reproducibility, with intraclass correlation coefficients exceeding 0.920. When used in combination with EIM, the MEA differentiated the affected muscles from the unaffected muscles in patients with neurogenic myopathy, by using EIM parameters of reactance and phase (p = 0.023 and 0.008, respectively). Thus, the novel MEA is a practical and reusable device for EIM assessment in cases of neurogenic myopathy. However, further refinement of the electrode is needed to enhance the clinical application of the system. PMID:26407702

  2. Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation.

    PubMed

    Pereira, Ulysse; Garcia-Le Gal, Caridad; Le Gal, Grégoire; Boulais, Nicholas; Lebonvallet, Nicolas; Dorange, Germaine; Lefeuvre, Luc; Gougerot, Agnés; Misery, Laurent

    2010-09-01

    Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.

  3. Mechanisms of nitric oxide-mediated, neurogenic vasodilation in mesenteric resistance arteries of toad Bufo marinus.

    PubMed

    Jennings, Brett L; Donald, John A

    2010-03-01

    This study determined the role of nitric oxide (NO) in neurogenic vasodilation in mesenteric resistance arteries of the toad Bufo marinus. NO synthase (NOS) was anatomically demonstrated in perivascular nerves, but not in the endothelium. ACh and nicotine caused TTX-sensitive neurogenic vasodilation of mesenteric arteries. The ACh-induced vasodilation was endothelium-independent and was mediated by the NO/soluble guanylyl cyclase signaling pathway, inasmuch as the vasodilation was blocked by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and the NOS inhibitors N(omega)-nitro-l-arginine methyl ester and N(omega)-nitro-l-arginine. Furthermore, the ACh-induced vasodilation was significantly decreased by the more selective neural NOS inhibitor N(5)-(1-imino-3-butenyl)-l-ornithine. The nicotine-induced vasodilation was endothelium-independent and mediated by NO and calcitonin gene-related peptide (CGRP), inasmuch as pretreatment of mesenteric arteries with a combination of N(omega)-nitro-l-arginine and the CGRP receptor antagonist CGRP-(8-37) blocked the vasodilation. Clotrimazole significantly decreased the ACh-induced response, providing evidence that a component of the NO vasodilation involved Ca(2+)-activated K(+) or voltage-gated K(+) channels. These data show that NO control of mesenteric resistance arteries of toad is provided by nitrergic nerves, rather than the endothelium, and implicate NO as a potentially important regulator of gut blood flow and peripheral blood pressure. PMID:20071617

  4. The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

    PubMed Central

    Guan, Yong; Wendong, Sun; Zhao, Shengtian; Liu, Tongyan; Liu, Yuqiang; Zhang, Xiulin; Yuan, Mingzhen

    2015-01-01

    ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED. PMID:26689522

  5. Specialized stem cell niche enables repetitive renewal of alligator teeth.

    PubMed

    Wu, Ping; Wu, Xiaoshan; Jiang, Ting-Xin; Elsey, Ruth M; Temple, Bradley L; Divers, Stephen J; Glenn, Travis C; Yuan, Kuo; Chen, Min-Huey; Widelitz, Randall B; Chuong, Cheng-Ming

    2013-05-28

    Reptiles and fish have robust regenerative powers for tooth renewal. However, extant mammals can either renew their teeth one time (diphyodont dentition) or not at all (monophyodont dentition). Humans replace their milk teeth with permanent teeth and then lose their ability for tooth renewal. Here, we study tooth renewal in a crocodilian model, the American alligator, which has well-organized teeth similar to mammals but can still undergo life-long renewal. Each alligator tooth is a complex family unit composed of the functional tooth, successional tooth, and dental lamina. Using multiple mitotic labeling, we map putative stem cells to the distal enlarged bulge of the dental lamina that contains quiescent odontogenic progenitors that can be activated during physiological exfoliation or artificial extraction. Tooth cycle initiation correlates with β-catenin activation and soluble frizzled-related protein 1 disappearance in the bulge. The dermal niche adjacent to the dermal lamina dynamically expresses neural cell adhesion molecule, tenascin-C, and other molecules. Furthermore, in development, asymmetric β-catenin localization leads to the formation of a heterochronous and complex tooth family unit configuration. Understanding how these signaling molecules interact in tooth development in this model may help us to learn how to stimulate growth of adult teeth in mammals.

  6. Available Climate Regimes Drive Niche Diversification during Range Expansion.

    PubMed

    Wüest, Rafael O; Antonelli, Alexandre; Zimmermann, Niklaus E; Linder, H Peter

    2015-05-01

    Climate is a main predictor of biodiversity on a global scale, yet how climate availability affects niche evolution remains poorly explored. Here we assess how intercontinental climate differences may affect the evolution of climate niches and suggest three possible processes: niche truncation along major environmental gradients, intercontinental differences in available climate causing differences in selective regimes, and niche shifts associated with long-distance dispersals leading to a pattern of punctuated evolution. Using the globally distributed danthonioid grasses, we show significant niche differentiation among continents and several instances of niche truncation. The comparison of inferred selective regimes with differences in available climatic space among continents demonstrates adaptation resulting from opportunistic evolution toward available climatic space. Our results suggest that niche evolution in this clade is punctuated, consistent with accelerated niche evolution after long-distance dispersal events. Finally, we discuss how intrinsic constraints (genetic, developmental, or functional) and biotic interactions could have interacted with these three processes during range expansion. Integrating these mechanisms could improve predictions for invasive taxa and long-term evolutionary responses of expanding clades to climate change.

  7. 28. VIEW OF THE SOLDERING NICHE FORMED WITH BRICKS. THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. VIEW OF THE SOLDERING NICHE FORMED WITH BRICKS. THE BACK OF THE NICHE IS CEMENT FINISHED. THE BOTTOM HAS A 1 INCH THICK ASBESTOS SHELF. THIS PHOTO WAS TAKEN AT THE 3RD FLOOR. - Pacific Telephone & Telegraph Company Building, 1519 Franklin Street, Oakland, Alameda County, CA

  8. Intraspecific genetic variation and competition interact to influence niche expansion

    PubMed Central

    Agashe, Deepa; Bolnick, Daniel I.

    2010-01-01

    Theory and empirical evidence show that intraspecific competition can drive selection favouring the use of novel resources (i.e. niche expansion). The evolutionary response to such selection depends on genetic variation for resource use. However, while genetic variation might facilitate niche expansion, genetically diverse groups may also experience weaker competition, reducing density-dependent selection on resource use. Therefore, genetic variation for fitness on different resources could directly facilitate, or indirectly retard, niche expansion. To test these alternatives, we factorially manipulated both the degree of genetic variation and population density in flour beetles (Tribolium castaneum) exposed to both novel and familiar food resources. Using stable carbon isotope analysis, we measured temporal change and individual variation in beetle diet across eight generations. Intraspecific competition and genetic variation acted on different components of niche evolution: competition facilitated niche expansion, while genetic variation increased individual variation in niche use. In addition, genetic variation and competition together facilitated niche expansion, but all these impacts were temporally variable. Thus, we show that the interaction between genetic variation and competition can also determine niche evolution at different time scales. PMID:20462902

  9. Melanosomes foster a tumour niche by activating CAFs.

    PubMed

    García-Silva, Susana; Peinado, Héctor

    2016-08-30

    Extracellular vesicles, such as exosomes, are important effectors in the formation of tumour-fostering niches. Pigmented melanosomes are now shown to have a relevant role in establishing a tumour niche in primary melanoma by reprogramming dermal fibroblasts into cancer-associated fibroblasts through the transfer of miR-211. PMID:27571736

  10. Using specialty advertising in a niche marketing plan.

    PubMed

    Schwisow, C R

    1992-01-01

    While niche marketing is not a new strategy, an increasing number of competitors are pursuing the same niches, resulting in stiff competition within the health care industry, writes C. Ronald Schwisow. This means marketers need to be resourceful to maximize their communications efforts. One such approach is specialty advertising.

  11. Spatial effects favour the evolution of niche construction.

    PubMed

    Silver, Matt; Di Paolo, Ezequiel

    2006-12-01

    We present an individual-based, spatial implementation of an existing two-locus population genetic model of niche construction. Our analysis reveals that, across a broad range of conditions, niche-construction traits can drive themselves to fixation by simultaneously generating selection that favours 'recipient' trait alleles and linkage disequilibrium between niche-construction and recipient trait alleles. The effect of spatiality is key, since it is the local, resource-mediated interaction between recipient and niche-constructing loci which gives rise to gene linkage. Spatial clustering effects point to a possible mechanism by which an initially rare recipient trait whose selection depends on niche construction could establish in an otherwise hostile environment. The same mechanism could also lead to the spread of an established niche-constructing colony. Similar phenomena are observed in the spatial modelling of two species 'engineering webs'. Here, the activities of two niche-constructing species can combine to drive a particular recipient trait to fixation, or in certain circumstances, maintain the presence of polymorphisms through the preservation of otherwise deleterious alleles. This may have some relevance to ecosystem stability and the maintenance of genetic variation, where the frequencies of key resources are affected by the niche-constructing activities of more than one species. Our model suggests that the stability of multi-species webs in natural populations may increase as the complexity of species-environment interactions increases.

  12. Overcoming Barriers for "Niche" Learners Through Distance Education.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; Hyatt, Sue Y.; Brennan, Joyce; Bertani, Raymond; Trevor, Thomas

    1999-01-01

    Focuses on students who fit into "niches," and discusses how the Chattanooga State Technical Community College's distance-learning program accommodates these learners. Describes five "niche" learner categories: students with disabilities, power-line maintenance technicians, emergency-service personnel, truckers, and industrial maintenance workers…

  13. Stage-specific control of niche positioning and integrity in the Drosophila testis.

    PubMed

    Schardt, Lisa; Ander, Janina-Jacqueline; Lohmann, Ingrid; Papagiannouli, Fani

    2015-11-01

    A fundamental question is how complex structures are maintained after their initial specification. Stem cells reside in a specialized microenvironment, called niche, which provides essential signals controlling stem cell behavior. We addressed this question by studying the Drosophila male stem cell niche, called the hub. Once specified, the hub cells need to maintain their position and architectural integrity through embryonic, larval and pupal stages of testis organogenesis and during adult life. The Hox gene Abd-B, in addition to its described role in male embryonic gonads, maintains the architecture and positioning of the larval hub from the germline by affecting integrin localization in the neighboring somatic cyst cells. We find that the AbdB-Boss/Sev cascade affects integrin independent of Talin, while genetic interactions depict integrin as the central downstream player in this system. Focal adhesion and integrin-adaptor proteins within the somatic stem cells and cyst cells, such as Paxillin, Pinch and Vav, also contribute to proper hub integrity and positioning. During adult stages, hub positioning is controlled by Abd-B activity in the outer acto-myosin sheath, while Abd-B expression in adult spermatocytes exerts no effect on hub positioning and integrin localization. Our data point at a cell- and stage-specific function of Abd-B and suggest that the occurrence of new cell types and cell interactions in the course of testis organogenesis made it necessary to adapt the whole system by reusing the same players for male stem cell niche positioning and integrity in an alternative manner.

  14. The zoophilic fruitfly Phortica variegata: morphology, ecology and biological niche.

    PubMed

    Otranto, D; Brianti, E; Cantacessi, C; Lia, R P; Máca, J

    2006-12-01

    Flies belonging to the subfamily Steganinae (Drosophilidae) display unusual zoophilic feeding habits at the adult and/or larval stage. Phortica variegata (Fallén) feeds on tears or eye liquid around the eyes of humans and carnivores. When feeding it is a potential vector of Thelazia callipaeda (Railliet and Henry) eyeworms. Adult and larval stages of this fly may be easily confused with other species belonging to the same genus, and little is known on the biology and ecology of P. variegata. In April-November 2005, a total of 969 P. variegata were collected in an area with a high prevalence of canine thelaziosis. The number of flies collected weekly was then related to climatic and environmental parameters (e.g. temperature, relative humidity and total rainfall) recorded daily at the collection site. The highest number of Phortica were collected during July-August. The sex ratio (number of males : females) rose from approximately 0.5 during May-July, to approximately 3.0 in August and 181 during September-October. Distributional data, representing 242 sites at which P. variegata has been collected in Europe, were analysed using a desktop implementation of the genetic algorithm for rule-set prediction (GARP) to model ecological requirements across Europe, as well as in Italy. P. variegata is shown to be mainly active at 20-25 degrees C and 50-75% RH. The ecological niche model suggests with a high degree of confidence that large areas of Europe are likely to represent suitable habitat for this species, mostly concentrated in central Europe. The results reported here contribute basic knowledge on the ecology and geographical distribution of P. variegata flies, which will be fundamental to gaining a better understanding of their role as vectors of human and animal pathogens. PMID:17199746

  15. Lottery coexistence on rocky shores: weak niche differentiation or equal competitors engaged in neutral dynamics?

    PubMed

    Shinen, Jennifer L; Navarrete, Sergio A

    2014-03-01

    Reconciling how niche and neutral processes may be important in species coexistence has revealed two important weaknesses in our collective understanding of species diversity: few empirical studies have determined whether species are truly coexisting, and fewer still have properly evaluated whether coexistence is achieved through niche differentiation or ecological equivalence. Here, we ask whether two common barnacles, Jehlius cirratus and Notochthamalus scabrosus, coexist locally and whether the slight but persistent differences in their distribution provide sufficient fitness trade-offs to overcome differences in competition. Both species recovered after experimental reduction; that is, they coexist, with no indication of hierarchical exclusion. No fitness inequalities affected species performance or interference effects on vital rates at any shore level, indicating no trade-offs in intra-interspecific effects across the ecological gradient. Additionally, no relationship was found between per capita population growth rates of either species with its own relative abundance; that is, neither species has a demographic advantage when rare. Instead, a lottery for space during settlement largely determines species' distributions, evidenced by the positive correlation across sites and tidal elevations between the relative abundances of adults and the recruits of the prior season. We conclude that Jehlius and Notochthamalus coexist neutrally, or nearly so, but discuss whether small, nonsignificant, and probably ephemeral fitness differences, which are inconsistent across the tidal gradient, could provide enough niche differentiation to promote coexistence.

  16. Ank3-dependent SVZ niche assembly is required for the continued production of new neurons

    PubMed Central

    Paez-Gonzalez, Patricia; Abdi, Khadar; Luciano, Dominic; Liu, Yan; Soriano-Navarro, Mario; Rawlins, Emma; Bennett, Vann; Garcia-Verdugo, Jose; Kuo, Chay T.

    2011-01-01

    SUMMARY The rodent subventricular/subependymal zone (SVZ/SEZ) houses neural stem cells (NSCs) that generate olfactory bulb interneurons. It is unclear how the SVZ environment sustains neuronal production into adulthood. We discovered that the adapter molecule Ankyrin-3 (Ank3) is specifically upregulated in radial glia destined to become SVZ ependymal niche cells, but not in NSCs, and is required for SVZ assembly through progenitor lateral adhesion. Furthermore, we found that Ank3 expression is controlled by Foxj1, a transcriptional regulator of multicilia formation, and genetic deletion of this pathway led to complete loss of SVZ niche structure. In its absence, radial glia continued to transition into postnatal NSCs. However, inducible ependymal deletion of Foxj1-Ank3 after SVZ niche assembly resulted in dramatic depletion of neurogenesis. Targeting a novel pathway regulating ependymal organization/assembly and showing its requirement for new neuron production, our results have important implications for environmental control of adult neurogenesis and harvesting NSCs for replacement therapy. PMID:21745638

  17. WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation.

    PubMed

    Ouspenskaia, Tamara; Matos, Irina; Mertz, Aaron F; Fiore, Vincent F; Fuchs, Elaine

    2016-01-14

    Adult stem cell (SC) maintenance and differentiation are known to depend on signals received from the niche. Here, however, we demonstrate a mechanism for SC specification and regulation that is niche independent. Using immunofluorescence, live imaging, genetics, cell-cycle analyses, in utero lentiviral transduction, and lineage-tracing, we show that in developing hair buds, SCs are born from asymmetric divisions that differentially display WNT and SHH signaling. Displaced WNT(lo) suprabasal daughters become SCs that respond to paracrine SHH and symmetrically expand. By contrast, basal daughters remain WNT(hi). They express but do not respond to SHH and hence maintain slow-cycling, asymmetric divisions. Over time, they become short-lived progenitors, generating differentiating daughters rather than SCs. Thus, in contrast to an established niche that harbors a fixed SC pool whose expelled progeny differentiate, asymmetric divisions first specify and displace early SCs into an environment conducive to expansion and later restrict their numbers by switching asymmetric fates. PMID:26771489

  18. Tis21 is required for adult neurogenesis in the subventricular zone and for olfactory behavior regulating cyclins, BMP4, Hes1/5 and Ids.

    PubMed

    Farioli-Vecchioli, Stefano; Ceccarelli, Manuela; Saraulli, Daniele; Micheli, Laura; Cannas, Sara; D'Alessandro, Francesca; Scardigli, Raffaella; Leonardi, Luca; Cinà, Irene; Costanzi, Marco; Mattera, Andrea; Cestari, Vincenzo; Tirone, Felice

    2014-01-01

    Bone morphogenic proteins (BMPs) and the Notch pathway regulate quiescence and self-renewal of stem cells of the subventricular zone (SVZ), an adult neurogenic niche. Here we analyze the role at the intersection of these pathways of Tis21 (Btg2/PC3), a gene regulating proliferation and differentiation of adult SVZ stem and progenitor cells. In Tis21-null SVZ and cultured neurospheres, we observed a strong decrease in the expression of BMP4 and its effectors Smad1/8, while the Notch anti-neural mediators Hes1/5 and the basic helix-loop-helix (bHLH) inhibitors Id1-3 increased. Consistently, expression of the proneural bHLH gene NeuroD1 decreased. Moreover, cyclins D1/2, A2, and E were strongly up-regulated. Thus, in the SVZ Tis21 activates the BMP pathway and inhibits the Notch pathway and the cell cycle. Correspondingly, the Tis21-null SVZ stem cells greatly increased; nonetheless, the proliferating neuroblasts diminished, whereas the post-mitotic neuroblasts paradoxically accumulated in SVZ, failing to migrate along the rostral migratory stream to the olfactory bulb. The ability, however, of neuroblasts to migrate from SVZ explants was not affected, suggesting that Tis21-null neuroblasts do not migrate to the olfactory bulb because of a defect in terminal differentiation. Notably, BMP4 addition or Id3 silencing rescued the defective differentiation observed in Tis21-null neurospheres, indicating that they mediate the Tis21 pro-differentiative action. The reduced number of granule neurons in the Tis21-null olfactory bulb led to a defect in olfactory detection threshold, without effect on olfactory memory, also suggesting that within olfactory circuits new granule neurons play a primary role in odor sensitivity rather than in memory.

  19. Niche divergence accelerates evolution in Asian endemic Procapra gazelles

    PubMed Central

    Hu, Junhua; Jiang, Zhigang; Chen, Jing; Qiao, Huijie

    2015-01-01

    Ecological niche divergence and adaptation to new environments are thought to play important roles in driving speciation. Whether recently evolved species show evidence for niche divergence or conservation is vital towards understanding the role of ecology in the process of speciation. The genus Procapra is an ancient, monophyletic lineage endemic to Asia that contains three extant species (P. gutturosa, P. przewalskii and P. picticaudata). These species mainly inhabit the Qinghai-Tibetan and Mongolian Plateaus, and today have primarily allopatric distributions. We applied a series of geographic information system–based analyses to test for environmental variation and niche divergence among these three species. We found substantial evidence for niche divergence in species’ bioclimatic preferences, which supports the hypothesis that niche divergence accelerates diversification in Procapra. Our results provide important insight into the evolutionary history of ungulates in Asia and help to elucidate how environmental changes accelerate lineage diversification. PMID:25951051

  20. Unifying niche shift studies: insights from biological invasions.

    PubMed

    Guisan, Antoine; Petitpierre, Blaise; Broennimann, Olivier; Daehler, Curtis; Kueffer, Christoph

    2014-05-01

    Assessing whether the climatic niche of a species may change between different geographic areas or time periods has become increasingly important in the context of ongoing global change. However, approaches and findings have remained largely controversial so far, calling for a unification of methods. Here, we build on a review of empirical studies of invasion to formalize a unifying framework that decomposes niche change into unfilling, stability, and expansion situations, taking both a pooled range and range-specific perspective on the niche, while accounting for climatic availability and climatic analogy. This framework provides new insights into the nature of climate niche shifts and our ability to anticipate invasions, and may help in guiding the design of experiments for assessing causes of niche changes.

  1. Niche divergence accelerates evolution in Asian endemic Procapra gazelles.

    PubMed

    Hu, Junhua; Jiang, Zhigang; Chen, Jing; Qiao, Huijie

    2015-01-01

    Ecological niche divergence and adaptation to new environments are thought to play important roles in driving speciation. Whether recently evolved species show evidence for niche divergence or conservation is vital towards understanding the role of ecology in the process of speciation. The genus Procapra is an ancient, monophyletic lineage endemic to Asia that contains three extant species (P. gutturosa, P. przewalskii and P. picticaudata). These species mainly inhabit the Qinghai-Tibetan and Mongolian Plateaus, and today have primarily allopatric distributions. We applied a series of geographic information system-based analyses to test for environmental variation and niche divergence among these three species. We found substantial evidence for niche divergence in species' bioclimatic preferences, which supports the hypothesis that niche divergence accelerates diversification in Procapra. Our results provide important insight into the evolutionary history of ungulates in Asia and help to elucidate how environmental changes accelerate lineage diversification. PMID:25951051

  2. Niche construction initiates the evolution of mutualistic interactions.

    PubMed

    Buser, Claudia C; Newcomb, Richard D; Gaskett, Anne C; Goddard, Matthew R

    2014-10-01

    Niche construction theory explains how organisms' niche modifications may feed back to affect their evolutionary trajectories. In theory, the evolution of other species accessing the same modified niche may also be affected. We propose that this niche construction may be a general mechanism driving the evolution of mutualisms. Drosophilid flies benefit from accessing yeast-infested fruits, but the consequences of this interaction for yeasts are unknown. We reveal high levels of variation among strains of Saccharomyces cerevisiae in their ability to modify fruits and attract Drosophila simulans. More attractive yeasts are dispersed more frequently, both in the lab and in the field, and flies associated with more attractive yeasts have higher fecundity. Although there may be multiple natural yeast and fly species interactions, our controlled assays in the lab and field provide evidence of a mutualistic interaction, facilitated by the yeast's niche modification.

  3. Differential niche dynamics among major marine invertebrate clades

    PubMed Central

    Hopkins, Melanie J; Simpson, Carl; Kiessling, Wolfgang

    2014-01-01

    The degree to which organisms retain their environmental preferences is of utmost importance in predicting their fate in a world of rapid climate change. Notably, marine invertebrates frequently show strong affinities for either carbonate or terrigenous clastic environments. This affinity is due to characteristics of the sediments as well as correlated environmental factors. We assessed the conservatism of substrate affinities of marine invertebrates over geological timescales, and found that niche conservatism is prevalent in the oceans, and largely determined by the strength of initial habitat preference. There is substantial variation in niche conservatism among major clades with corals and sponges being among the most conservative. Time-series analysis suggests that niche conservatism is enhanced during times of elevated nutrient flux, whereas niche evolution tends to occur after mass extinctions. Niche evolution is not necessarily elevated in genera exhibiting higher turnover in species composition. PMID:24313951

  4. [Characteristics, dynamics and niche of insect community in plum orchard].

    PubMed

    Huang, Baohong; Zou, Yunding; Bi, Shoudong; Li, Hengkui; Zhu, Qiaoli

    2005-02-01

    The insect community in plum orchard was investigated on organization level and temporal-spatial niche. The results showed that the insect community was abundant, which included 6 orders, 23 families. The individuals of species, diversity indices, and evenness increased with time. Myzus persicae and Asiaarposina sasokii had the widest spatial niche breadth, while Didesmococcus koreauus borchs had the widest temporal niche breadth. Among the natural enemies, Chilocorus rubidus had the widest both temporal and spatial niche breadth. The niche of Chicocorus rubidus and Didesmococcus koreauus overlapped larger than that of the others, which indicated their synchrony in temporal dimension and their similarity in spatial dimension. As the dominant natural enemies, the two populations should be protected and utilized to control plum pest.

  5. Neurogenic Stuttering

    MedlinePlus

    ... Facts FAQ Basic Research Resources Brochures Free E-Books Free Videos Webinars Blog Referral Lists Newsletters Check your Library Books on Stuttering Product LIst Links Translations Podcasts Press ...

  6. Neurogenic bladder

    MedlinePlus

    ... of underactive bladder: Full bladder and possibly urine leakage Inability to tell when the bladder is full ... Constant urine leakage can cause skin to break down and lead to pressure sores Kidney damage may occur if the bladder ...

  7. NICHE: The non-imaging Cherenkov array

    NASA Astrophysics Data System (ADS)

    Bergman, Douglas; Krizmanic, John

    2013-02-01

    The accurate measurement of the Cosmic Ray (CR) nuclear composition around and above the Knee (~ 1015.5 eV) has been difficult due to uncertainties inherent to the measurement techniques and/or dependence on hadronic Monte Carlo simulation models required to interpret the data. Measurement of the Cherenkov air shower signal, calibrated with air fluorescence measurements, offers a methodology to provide an accurate measurement of the nuclear composition evolution over a large energy range. NICHE will use an array of widely-spaced, non-imaging Cherenkov counters to measure the amplitude and time-spread of the air shower Cherenkov signal to extract CR nuclear composition measurements and to cross-calibrate the Cherenkov energy and composition measurements with TA/TALE fluorescence and surface detector measurements.

  8. Exometabolite niche partitioning among sympatric soil bacteria

    SciTech Connect

    Baran, Richard; Brodie, Eoin L.; Mayberry-Lewis, Jazmine; Hummel, Eric; Da Rocha, Ulisses Nunes; Chakraborty, Romy; Bowen, Benjamin P.; Karaoz, Ulas; Cadillo-Quiroz, Hinsby; Garcia-Pichel, Ferran; Northen, Trent R.

    2015-09-22

    Soils are arguably the most microbially diverse ecosystems. Physicochemical properties have been associated with the maintenance of this diversity. Yet, the role of microbial substrate specialization is largely unexplored since substrate utilization studies have focused on simple substrates, not the complex mixtures representative of the soil environment. Here we examine the exometabolite composition of desert biological soil crusts (biocrusts) and the substrate preferences of seven biocrust isolates. The biocrust's main primary producer releases a diverse array of metabolites, and isolates of physically associated taxa use unique subsets of the complex metabolite pool. Individual isolates use only 13-26% of available metabolites, with only 2 out of 470 used by all and 40% not used by any. An extension of this approach to a mesophilic soil environment also reveals high levels of microbial substrate specialization. In conclusion, these results suggest that exometabolite niche partitioning may be an important factor in the maintenance of microbial diversity.

  9. Exometabolite niche partitioning among sympatric soil bacteria

    PubMed Central

    Baran, Richard; Brodie, Eoin L.; Mayberry-Lewis, Jazmine; Hummel, Eric; Da Rocha, Ulisses Nunes; Chakraborty, Romy; Bowen, Benjamin P.; Karaoz, Ulas; Cadillo-Quiroz, Hinsby; Garcia-Pichel, Ferran; Northen, Trent R.

    2015-01-01

    Soils are arguably the most microbially diverse ecosystems. Physicochemical properties have been associated with the maintenance of this diversity. Yet, the role of microbial substrate specialization is largely unexplored since substrate utilization studies have focused on simple substrates, not the complex mixtures representative of the soil environment. Here we examine the exometabolite composition of desert biological soil crusts (biocrusts) and the substrate preferences of seven biocrust isolates. The biocrust's main primary producer releases a diverse array of metabolites, and isolates of physically associated taxa use unique subsets of the complex metabolite pool. Individual isolates use only 13−26% of available metabolites, with only 2 out of 470 used by all and 40% not used by any. An extension of this approach to a mesophilic soil environment also reveals high levels of microbial substrate specialization. These results suggest that exometabolite niche partitioning may be an important factor in the maintenance of microbial diversity. PMID:26392107

  10. Exometabolite niche partitioning among sympatric soil bacteria

    DOE PAGES

    Baran, Richard; Brodie, Eoin L.; Mayberry-Lewis, Jazmine; Hummel, Eric; Da Rocha, Ulisses Nunes; Chakraborty, Romy; Bowen, Benjamin P.; Karaoz, Ulas; Cadillo-Quiroz, Hinsby; Garcia-Pichel, Ferran; et al

    2015-09-22

    Soils are arguably the most microbially diverse ecosystems. Physicochemical properties have been associated with the maintenance of this diversity. Yet, the role of microbial substrate specialization is largely unexplored since substrate utilization studies have focused on simple substrates, not the complex mixtures representative of the soil environment. Here we examine the exometabolite composition of desert biological soil crusts (biocrusts) and the substrate preferences of seven biocrust isolates. The biocrust's main primary producer releases a diverse array of metabolites, and isolates of physically associated taxa use unique subsets of the complex metabolite pool. Individual isolates use only 13-26% of available metabolites,more » with only 2 out of 470 used by all and 40% not used by any. An extension of this approach to a mesophilic soil environment also reveals high levels of microbial substrate specialization. In conclusion, these results suggest that exometabolite niche partitioning may be an important factor in the maintenance of microbial diversity.« less

  11. Pathogen evolution and the immunological niche

    PubMed Central

    Cobey, Sarah

    2014-01-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible–infected–recovered (SIR) model. However, there is growing evidence that the complexity of many host–pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

  12. Animal personality due to social niche specialisation.

    PubMed

    Bergmüller, Ralph; Taborsky, Michael

    2010-09-01

    The existence of 'animal personality', i.e. consistent individual differences in behaviour across time and contexts, is an evolutionary puzzle that has recently generated considerable research interest. Although social factors are generally considered to be important, it is as yet unclear how they might select for personality. Drawing from ecological niche theory, we explore how social conflict and alternative social options can be key factors in the evolution and development of consistent individual differences in behaviour. We discuss how animal personality research might benefit from insights into the study of alternative tactics and illustrate how selection can favour behavioural diversification and consistency due to fitness benefits resulting from conflict reduction among social partners.

  13. Language, embodiment, and the cognitive niche.

    PubMed

    Clark, Andy

    2006-08-01

    Embodied agents use bodily actions and environmental interventions to make the world a better place to think in. Where does language fit into this emerging picture of the embodied, ecologically efficient agent? One useful way to approach this question is to consider language itself as a cognition-enhancing animal-built structure. To take this perspective is to view language as a kind of self-constructed cognitive niche: a persisting but never stationary material scaffolding whose crucial role in promoting thought and reason remains surprisingly poorly understood. It is the very materiality of this linguistic scaffolding, I suggest, that gives it some key benefits. By materializing thought in words, we create structures that are themselves proper objects of perception, manipulation, and (further) thought.

  14. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

    PubMed Central

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

  15. Genetic basis for developmental homeostasis of germline stem cell niche number: a network of Tramtrack-Group nuclear BTB factors.

    PubMed

    Bartoletti, Mathieu; Rubin, Thomas; Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

    2012-01-01

    The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8-10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches.

  16. Ecology of Enterococcus faecalis and niche adapted or non-niche-adapted Enterococcus faecium in continuous-flow anaerobic cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To study the survivability of niche adapted Enterococcus faecium I.3rif (I.3rif) vs. non-niche adapted Enterococcus faecium (GRE47) in cultures that contain Enterococcus faecalis I.2. Methods: An anaerobic continuous-flow culture of chicken microflora (CCF) that models the chicken gastr...

  17. Using Ecological Niche Models and Niche Analyses to Understand Speciation Patterns: The Case of Sister Neotropical Orchid Bees

    PubMed Central

    Silva, Daniel P.; Vilela, Bruno; De Marco, Paulo; Nemésio, André

    2014-01-01

    The role of past connections between the two major South American forested biomes on current species distribution has been recognized a long time ago. Climatic oscillations that further separated these biomes have promoted parapatric speciation, in which many species had their continuous distribution split, giving rise to different but related species (i.e., different potential distributions and realized niche features). The distribution of many sister species of orchid bees follow this pattern. Here, using ecological niche models and niche analyses, we (1) tested the role of ecological niche differentiation on the divergence between sister orchid-bees (genera Eulaema and Eufriesea) from the Amazon and Atlantic forests, and (2) highlighted interesting areas for new surveys. Amazonian species occupied different realized niches than their Atlantic sister species. Conversely, species of sympatric but distantly related Eulaema bees occupied similar realized niches. Amazonian species had a wide potential distribution in South America, whereas Atlantic Forest species were more limited to the eastern coast of the continent. Additionally, we identified several areas in need of future surveys. Our results show that the realized niche of Atlantic-Amazonian sister species of orchid bees, which have been previously treated as allopatric populations of three species, had limited niche overlap and similarity. These findings agree with their current taxonomy, which treats each of those populations as distinct valid species. PMID:25422941

  18. A mathematical model of salt-sensitive hypertension: the neurogenic hypothesis

    PubMed Central

    Averina, Viktoria A; Othmer, Hans G; Fink, Gregory D; Osborn, John W

    2015-01-01

    Salt sensitivity of arterial pressure (salt-sensitive hypertension) is a serious global health issue. The causes of salt-sensitive hypertension are extremely complex and mathematical models can elucidate potential mechanisms that are experimentally inaccessible. Until recently, the only mathematical model for long-term control of arterial pressure was the model of Guyton and Coleman; referred to as the G-C model. The core of this model is the assumption that sodium excretion is driven by renal perfusion pressure, the so-called ‘renal function curve’. Thus, the G-C model dictates that all forms of hypertension are due to a primary shift of the renal function curve to a higher operating pressure. However, several recent experimental studies in a model of hypertension produced by the combination of a high salt intake and administration of angiotensin II, the AngII–salt model, are inconsistent with the G-C model. We developed a new mathematical model that does not limit the cause of salt-sensitive hypertension solely to primary renal dysfunction. The model is the first known mathematical counterexample to the assumption that all salt-sensitive forms of hypertension require a primary shift of renal function: we show that in at least one salt-sensitive form of hypertension the requirement is not necessary. We will refer to this computational model as the ‘neurogenic model’. In this Symposium Review we discuss how, despite fundamental differences between the G-C model and the neurogenic model regarding mechanisms regulating sodium excretion and vascular resistance, they generate similar haemodynamic profiles of AngII–salt hypertension. In addition, the steady-state relationships between arterial pressure and sodium excretion, a correlation that is often erroneously presented as the ‘renal function curve’, are also similar in both models. Our findings suggest that salt-sensitive hypertension is not due solely to renal dysfunction, as predicted by the G

  19. The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin.

    PubMed

    Banki, E; Hajna, Zs; Kemeny, A; Botz, B; Nagy, P; Bolcskei, K; Toth, G; Reglodi, D; Helyes, Zs

    2014-10-01

    We have earlier shown that PACAP-38 decreases neurogenic inflammation. However, there were no data on its receptorial mechanism and the involvement of its PAC1 and VPAC1/2 receptors (PAC1R, VPAC1/2R) in this inhibitory effect. Neurogenic inflammation in the mouse ear was induced by topical application of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor activator mustard oil (MO). Consequent neurogenic edema, vasodilation and plasma leakage were assessed by measuring ear thickness with engineer's micrometer, detecting tissue perfusion by laser Doppler scanning and Evans blue or indocyanine green extravasation by intravital videomicroscopy or fluorescence imaging, respectively. Myeloperoxidase activity, an indicator of neutrophil infiltration, was measured from the ear homogenates with spectrophotometry. The selective PAC1R agonist maxadilan, the VPAC1/2R agonist vasoactive intestinal polypeptide (VIP) or the vehicle were administered i.p. 15 min before MO. Substance P (SP) concentration of the ear was assessed by radioimmunoassay. Maxadilan significantly diminished MO-induced neurogenic edema, increase of vascular permeability and vasodilation. These inhibitory effects of maxadilan may be partially due to the decreased substance P (SP) levels. In contrast, inhibitory effect of VIP on ear swelling was moderate, without any effect on MO-induced plasma leakage or SP release, however, activation of VPAC1/2R inhibited the increased microcirculation caused by the early arteriolar vasodilation. Neither the PAC1R, nor the VPAC1/2R agonist influenced the MO-evoked increase in tissue myeloperoxidase activity. These results clearly show that PAC1R activation inhibits acute neurogenic arterial vasodilation and plasma protein leakage from the venules, while VPAC1/2R stimulation is only involved in the attenuation of vasodilation.

  20. Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury

    PubMed Central

    Pushchina, Evgeniya V.; Shukla, Sachin; Varaksin, Anatoly A.; Obukhov, Dmitry K.

    2016-01-01

    Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury. In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1–4 days of culture. The present findings suggest that trout can be used as a novel model for studying neuronal regeneration. PMID:27212918

  1. Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury.

    PubMed

    Pushchina, Evgeniya V; Shukla, Sachin; Varaksin, Anatoly A; Obukhov, Dmitry K

    2016-04-01

    Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury. In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1-4 days of culture. The present findings suggest that trout can be used as a novel model for studying neuronal regeneration. PMID:27212918

  2. Tempo and mode of climatic niche evolution in Primates.

    PubMed

    Duran, Andressa; Pie, Marcio R

    2015-09-01

    Climatic niches have increasingly become a nexus in our understanding of a variety of ecological and evolutionary phenomena, from species distributions to latitudinal diversity gradients. Despite the increasing availability of comprehensive datasets on species ranges, phylogenetic histories, and georeferenced environmental conditions, studies on the evolution of climate niches have only begun to understand how niches evolve over evolutionary timescales. Here, using primates as a model system, we integrate recently developed phylogenetic comparative methods, species distribution patterns, and climatic data to explore primate climatic niche evolution, both among clades and over time. In general, we found that simple, constant-rate models provide a poor representation of how climatic niches evolve. For instance, there have been shifts in the rate of climatic niche evolution in several independent clades, particularly in response to the increasingly cooler climates of the past 10 My. Interestingly, rate accelerations greatly outnumbered rate decelerations. These results highlight the importance of considering more realistic evolutionary models that allow for the detection of heterogeneity in the tempo and mode of climatic niche evolution, as well as to infer possible constraining factors for species distributions in geographical space. PMID:26178157

  3. Tempo and mode of climatic niche evolution in Primates.

    PubMed

    Duran, Andressa; Pie, Marcio R

    2015-09-01

    Climatic niches have increasingly become a nexus in our understanding of a variety of ecological and evolutionary phenomena, from species distributions to latitudinal diversity gradients. Despite the increasing availability of comprehensive datasets on species ranges, phylogenetic histories, and georeferenced environmental conditions, studies on the evolution of climate niches have only begun to understand how niches evolve over evolutionary timescales. Here, using primates as a model system, we integrate recently developed phylogenetic comparative methods, species distribution patterns, and climatic data to explore primate climatic niche evolution, both among clades and over time. In general, we found that simple, constant-rate models provide a poor representation of how climatic niches evolve. For instance, there have been shifts in the rate of climatic niche evolution in several independent clades, particularly in response to the increasingly cooler climates of the past 10 My. Interestingly, rate accelerations greatly outnumbered rate decelerations. These results highlight the importance of considering more realistic evolutionary models that allow for the detection of heterogeneity in the tempo and mode of climatic niche evolution, as well as to infer possible constraining factors for species distributions in geographical space.

  4. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  5. [Neurogenic bladder function disorders in patients with meningomyelocele: S2k guidelines on diagnostics and therapy].

    PubMed

    Stein, R; Assion, C; Beetz, R; Bürst, M; Cremer, R; Ermert, A; Goepel, M; Kuwertz-Bröking, E; Ludwikowski, B; Michael, T; Pannek, J; Peters, H; Rohrmann, D; Rübben, I; Schröder, A; Trollmann, R; Thüroff, J W; Wagner, W

    2015-02-01

    The treatment of children and adolescents with meningomyelocele has experienced a clear change in the last 30 years. The establishment of pharmacotherapy, clean intermittent catheterization (CIC) and infection prophylaxis have improved the prognosis for patients and have led to new therapeutic strategies. The interdisciplinary cooperation between neonatologists, neurosurgeons, pediatric neurologists, pediatric urologists, pediatric nephrologists, pediatric orthopedists and pediatric surgeons leads to optimization of individualized therapy. These guidelines present definitions and classifications, investigations and timing which are described in detail. The conservative and operative therapy options for neurogenic bladder function disorders are described and discussed with reference to the current literature. The brief overview provides in each case assistance for the treating physician in the care of this patient group and facilitates the interdisciplinary cooperation. PMID:25690576

  6. [Role of thermo TRP channels in cutaneous neurogenic inflammation and itch].

    PubMed

    XIE, Zhi-qiang

    2009-07-01

    The temperature-sensitive transient receptor potential (TRP) channels, is also called thermo TRP, including TRPV1, TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1, which are expressed in sensory neurons and non-neuronal cells (e.g.keratinocyte, mast cell) of the skin. Thermo TRP channels are activated/sensitized by physical and chemical mediators, which participate in thermosensation and thermoregulation, so that they are key players in pruritus or pain pathogenesis. Thermo TRP channels are also involved in cutaneous neurogenic inflammation, thus they are regarded as molecular targets for future therapy in skin inflammation, pruritus and pain. In addition, following a basic syntax and molecular substrate of nociception and pruriception established by TRP channels-centered concept, the sensory categories can be distinguished and re-defined. Thermo TRP