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Sample records for adult rat neocortex

  1. Cell migration in the rat embryonic neocortex.

    PubMed

    Bayer, S A; Altman, J; Russo, R J; Dai, X F; Simmons, J A

    1991-05-15

    Three-dimensional reconstructions of the normal rat embryonic (E) neocortex on days E15, E17, E19, and E21, using Skandha (software designed by J. Prothero, University of Washington, Seattle), show that the neocortical ventricular zone shrinks rapidly in the medial direction during cortical morphogenesis. [3H]thymidine autoradiography indicates that the shrinkage of the ventricular zone occurs before neurons in lateral and ventrolateral parts of layers IV-II are generated. Consequently, most of these neurons originate 400-1000 microns medial to their settling sites in the cortical plate. Embryos killed at daily intervals up to E21 after a single injection of [3H]thymidine on either E17 or E18 revealed the presence of a prominent migratory path, the lateral cortical stream, used by neurons migrating to the lateral and ventrolateral cortical plate; neurons migrating to the dorsal cortical plate follow a direct radial path. Arrival times of neurons in the cortical plate depend on the migratory path and are proportional to the overall distance travelled. Neurons that migrate only radially arrive in the dorsal cortical plate in two days (shortest route). Neurons that migrate laterally arrive in the lateral cortical plate in 3 days (longer route) and in the ventrolateral cortical plate in 4 days (longest route). [3H]thymidine autoradiography also shows that cells generated in the neocortical ventricular zone migrate in the lateral cortical stream for 5 or more days and accumulate in a reservoir. Cells leave the reservoir to enter the piriform cortex and destinations (as yet undetermined) in the basal telencephalon. The lateral cortical stream is found wherever the neocortical primordium surrounds the basal ganglia and is absent behind the basal ganglia. A computer analysis of nuclear orientation in anterior and posterior parts of the intermediate zone in the dorsal neocortex between days E17 and E22 shows that horizontally oriented nuclei are more common anteriorly where

  2. Long-Term Effects of Maternal Deprivation on the Neuronal Soma Area in the Rat Neocortex

    PubMed Central

    Aksić, Milan; Radonjić, Nevena V.; Aleksić, Dubravka; Jevtić, Gordana; Marković, Branka; Petronijević, Nataša; Radonjić, Vidosava; Filipović, Branislav

    2014-01-01

    Early separation of rat pups from their mothers (separatio a matrem) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group. The results of this study demonstrate that stress in early life has a long-term effect on neuronal soma size in cingulate and retrosplenial cortex and is potentially interesting as these structures play an important role in cognition. PMID:24895554

  3. Ontogeny of the serotonergic projection to rat neocortex: transient expression of a dense innervation to primary sensory areas

    SciTech Connect

    D'Amato, R.J.; Blue, M.E.; Largent, B.L.; Lynch, D.R.; Ledbetter, D.J.; Molliver, M.E.; Snyder, S.H.

    1987-06-01

    The development of serotonergic innervation to rat cerebral cortex was characterized by immunohistochemical localization of serotonin combined with autoradiographic imaging of serotonin-uptake sites. In neonatal rat, a transient, dense, serotonergic innervation appears in all primary sensory areas of cortex. In somatosensory cortex, dense patches of serotonergic innervation are aligned with specialized cellular aggregates called barrels. The dense patches are not apparent after 3 weeks of age, and the serotonergic innervation becomes more uniform in adult neocortex. This precocious neonatal serotonergic innervation may play a transient physiologic role in sensory areas of cortex or may exert a trophic influence on the development of cortical circuitry and thalamocortical connections.

  4. Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation

    PubMed Central

    Korogod, Natalya; Petersen, Carl CH; Knott, Graham W

    2015-01-01

    Analysis of brain ultrastructure using electron microscopy typically relies on chemical fixation. However, this is known to cause significant tissue distortion including a reduction in the extracellular space. Cryo fixation is thought to give a truer representation of biological structures, and here we use rapid, high-pressure freezing on adult mouse neocortex to quantify the extent to which these two fixation methods differ in terms of their preservation of the different cellular compartments, and the arrangement of membranes at the synapse and around blood vessels. As well as preserving a physiological extracellular space, cryo fixation reveals larger numbers of docked synaptic vesicles, a smaller glial volume, and a less intimate glial coverage of synapses and blood vessels compared to chemical fixation. The ultrastructure of mouse neocortex therefore differs significantly comparing cryo and chemical fixation conditions. DOI: http://dx.doi.org/10.7554/eLife.05793.001 PMID:26259873

  5. Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation.

    PubMed

    Korogod, Natalya; Petersen, Carl C H; Knott, Graham W

    2015-01-01

    Analysis of brain ultrastructure using electron microscopy typically relies on chemical fixation. However, this is known to cause significant tissue distortion including a reduction in the extracellular space. Cryo fixation is thought to give a truer representation of biological structures, and here we use rapid, high-pressure freezing on adult mouse neocortex to quantify the extent to which these two fixation methods differ in terms of their preservation of the different cellular compartments, and the arrangement of membranes at the synapse and around blood vessels. As well as preserving a physiological extracellular space, cryo fixation reveals larger numbers of docked synaptic vesicles, a smaller glial volume, and a less intimate glial coverage of synapses and blood vessels compared to chemical fixation. The ultrastructure of mouse neocortex therefore differs significantly comparing cryo and chemical fixation conditions. PMID:26259873

  6. Effects of Maternal Dietary Restriction of Vitamin B-6 on Neocortex Development in Rats

    NASA Astrophysics Data System (ADS)

    Groziak, Susan Marie

    The aim of this investigation was to quantitate the effects of a dietary restriction in Vitamin B-6 during gestation or gestation and lactation on neurogenesis, neuron longevity and neuron differentiation in the neocortex of rats. Sprague Dawley female rats were fed, ad libitum, a Vitamin B-6 free diet (AIN 76) supplemented with 0.0 or 0.6 mg pyridoxine (PN)/kg diet during gestation followed by a control level of 7.0 mg PN/kg diet during lactation, or were fed the Vitamin B-6 free diet supplemented with 0.6 or 7.0 mg PN/kg diet throughout gestation and lactation. The neocortex of progeny of these animals were examined at 30 days of age employing light and electron microscopy. Analyses of neurogenesis, neuron longevity and differentiation of neurons (size of somata, dendritic arborization and spine density in Golgi Cox preparations, and synaptic density in E.M. preparations) were conducted. Each of the Vitamin B-6 restricted treatments adversely affected neurogenesis, neuron longevity and neuron differentiation. The degree of adverse effects paralleled the severity (dose or duration) of the restriction imposed. Expressed as percentage reduction from control values, the findings indicated that neuron longevity and differentiation of neurons in the neocortex were more severely affected than neurogenesis by a maternal dietary restriction in Vitamin B-6.

  7. A dynamic zone defines interneuron remodeling in the adult neocortex

    PubMed Central

    Lee, Wei-Chung Allen; Chen, Jerry L.; Huang, Hayden; Leslie, Jennifer H.; Amitai, Yael; So, Peter T.; Nedivi, Elly

    2008-01-01

    The contribution of structural remodeling to long-term adult brain plasticity is unclear. Here, we investigate features of GABAergic interneuron dendrite dynamics and extract clues regarding its potential role in cortical function and circuit plasticity. We show that remodeling interneurons are contained within a “dynamic zone” corresponding to a superficial strip of layers 2/3, and remodeling dendrites respect the lower border of this zone. Remodeling occurs primarily at the periphery of dendritic fields with addition and retraction of new branch tips. We further show that dendrite remodeling is not intrinsic to a specific interneuron class. These data suggest that interneuron remodeling is not a feature predetermined by genetic lineage, but rather, it is imposed by cortical laminar circuitry. Our findings are consistent with dynamic GABAergic modulation of feedforward and recurrent connections in response to top-down feedback and suggest a structural component to functional plasticity of supragranular neocortical laminae. PMID:19066223

  8. Physiology and Impact of Horizontal Connections in Rat Neocortex.

    PubMed

    Schnepel, Philipp; Kumar, Arvind; Zohar, Mihael; Aertsen, Ad; Boucsein, Clemens

    2015-10-01

    Cortical information processing at the cellular level has predominantly been studied in local networks, which are dominated by strong vertical connectivity between layers. However, recent studies suggest that the bulk of axons targeting pyramidal neurons most likely originate from outside this local range, emphasizing the importance of horizontal connections. We mapped a subset of these connections to L5B pyramidal neurons in rat somatosensory cortex with photostimulation, identifying intact projections up to a lateral distance of 2 mm. Our estimates of the spatial distribution of cells presynaptic to L5B pyramids support the idea that the majority is located outside the local volume. The synaptic physiology of horizontal connections does not differ markedly from that of local connections, whereas the layer and cell-type-dependent pattern of innervation does. Apart from L2/3, L6A provides a strong source of horizontal connections. Implementing our data into a spiking neuronal network model shows that more horizontal connections promote robust asynchronous ongoing activity states and reduce noise correlations in stimulus-induced activity. PMID:25410428

  9. Impact of Injury Location and Severity on Posttraumatic Epilepsy in the Rat: Role of Frontal Neocortex

    PubMed Central

    Curia, Giulia; Levitt, Michael; Fender, Jason S.; Miller, John W.; Ojemann, Jeffrey

    2011-01-01

    Human posttraumatic epilepsy (PTE) is highly heterogeneous, ranging from mild remitting to progressive disabling forms. PTE results in simple partial, complex partial, and secondarily generalized seizures with a wide spectrum of durations and semiologies. PTE variability is thought to depend on the heterogeneity of head injury and patient's age, gender, and genetic background. To better understand the role of these factors, we investigated the seizures resulting from calibrated fluid percussion injury (FPI) to adolescent male Sprague–Dawley rats with video electrocorticography. We show that PTE incidence and the frequency and severity of chronic seizures depend on the location and severity of FPI. The frontal neocortex was more prone to epileptogenesis than the parietal and occipital, generating earlier, longer, and more frequent partial seizures. A prominent limbic focus developed in most animals, regardless of parameters of injury. Remarkably, even with carefully controlled injury parameters, including type, severity, and location, the duration of posttraumatic apnea and the age and gender of outbred rats, there was great subject-to-subject variability in frequency, duration, and rate of progression of seizures, indicating that other factors, likely the subjects' genetic background and physiological states, have critical roles in determining the characteristics of PTE. PMID:21112931

  10. Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

    PubMed

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-01-15

    Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. PMID:26433146

  11. Developmental Controls are Re-Expressed during Induction of Neurogenesis in the Neocortex of Young Adult Mice

    PubMed Central

    Sohur, U. Shivraj; Arlotta, Paola; Macklis, Jeffrey D.

    2012-01-01

    Whether induction of low-level neurogenesis in normally non-neurogenic regions of the adult brain mimics aspects of developmental neurogenesis is currently unknown. Previously, we and others identified that biophysically induced, neuron subtype-specific apoptosis in mouse neocortex results in induction of neurogenesis of limited numbers of subtype-appropriate projection neurons with axonal projections to either thalamus or spinal cord, depending on the neuron subtype activated to undergo targeted apoptosis. Here, we test the hypothesis that developmental genes from embryonic corticogenesis are re-activated, and that some of these genes might underlie induction of low-level adult neocortical neurogenesis. We directly investigated this hypothesis via microarray analysis of microdissected regions of young adult mouse neocortex undergoing biophysically activated targeted apoptosis of neocortical callosal projection neurons. We compared the microarray results identifying differentially expressed genes with public databases of embryonic developmental genes. We find that, following activation of subtype-specific neuronal apoptosis, three distinct sets of normal developmental genes are selectively re-expressed in neocortical regions of induced neurogenesis in young adult mice: (1) genes expressed by subsets of progenitors and immature neurons in the developing ventricular and/or subventricular zones; (2) genes normally expressed by developmental radial glial progenitors; and (3) genes involved in synaptogenesis. Together with previous results, the data indicate that at least some developmental molecular controls over embryonic neurogenesis can be re-activated in the setting of induction of neurogenesis in the young adult neocortex, and suggest that some of these activate and initiate adult neuronal differentiation from endogenous progenitor populations. Understanding molecular mechanisms contributing to induced adult neurogenesis might enable directed CNS repair. PMID

  12. Dysplastic neocortex and subcortical heterotopias in methylazoxymethanol-treated rats: an intracellular study of identified pyramidal neurones.

    PubMed

    Sancini, G; Franceschetti, S; Battaglia, G; Colacitti, C; Di Luca, M; Spreafico, R; Avanzini, G

    1998-05-01

    Intracellular recordings were obtained using biocytin-filled electrodes from 78 neurones located in both dysplastic neocortex and subcortical heterotopic aggregates in a model of neuronal migration disorder induced in rats by means of a double methylazoxymethanol injection given on embryonic day 15. Both regular spiking and intrinsically bursting pyramidal neurones were found in all of the examined structures and were synaptically activated by subcortical stimulation. In a neuronal subpopulation (22%) located in the neocortex as well as in the subcortical heterotopic aggregates, the injection of depolarising current pulses elicited aberrant firing patterns, consisting of repetitive bursts of APs that gradually increased in duration and eventually merged in a long-lasting discharge. The gradual development of this 'excessive' bursting behaviour suggests a progressive run-down of the slow components of the hyperpolarising afterpotential. PMID:9792622

  13. Expression of GABA A receptor alpha1 subunit mRNA and protein in rat neocortex following photothrombotic infarction.

    PubMed

    Kharlamov, Elena A; Downey, Kathy L; Jukkola, Peter I; Grayson, Dennis R; Kelly, Kevin M

    2008-05-19

    Photothrombotic infarcts of the neocortex result in structural and functional alterations of cortical networks, including decreased GABAergic inhibition, and can generate epileptic seizures within 1 month of lesioning. In our study, we assessed the involvement and potential changes of cortical GABA A receptor (GABA AR) alpha1 subunits at 1, 3, 7, and 30 days after photothrombosis. Quantitative competitive reverse transcription-polymerase chain reaction (cRT-PCR) and semi-quantitative Western blot analysis were used to investigate GABA AR alpha1 subunit mRNA and protein levels in proximal and distal regions of perilesional cortex and in homotopic areas of young adult Sprague-Dawley rats. GABA AR alpha1 subunit mRNA levels were decreased ipsilateral and contralateral to the infarct at 7 days, but were increased bilaterally at 30 days. GABA AR alpha1 subunit protein levels revealed no significant change in neocortical areas of both hemispheres of lesioned animals compared with protein levels of sham-operated controls at 1, 3, 7, and 30 days. At 30 days, GABA AR alpha1 subunit protein expression was significantly increased in lesioned animals within proximal and distal regions of perilesional cortex compared with distal neocortical areas contralaterally (Student's t-test, p<0.05). Short- and long-term alterations of mRNA and protein levels of the GABA AR alpha1 subunit ipsilateral and contralateral to the lesion may influence alterations in cell surface receptor subtype expression and GABA AR function following ischemic infarction and may be associated with formative mechanisms of poststroke epileptogenesis. PMID:18407248

  14. Cholinergic grafts in the neocortex or hippocampus of aged rats: reduction of delay-dependent deficits in the delayed non-matching to position task.

    PubMed

    Dunnett, S B; Badman, F; Rogers, D C; Evenden, J L; Iversen, S D

    1988-10-01

    Aged (24 month) rats have previously been shown to manifest delay-dependent deficits in the performance of an operant delayed non-matching to position task. In the present experiment, cholinergic-rich grafts implanted into either the neocortex or the hippocampus of aged rats are shown to reinnervate the host neocortex and hippocampus, respectively, and to provide a significant amelioration of the host animals' short-term memory impairments. The results are discussed in light of the cholinergic hypothesis of geriatric memory dysfunction. PMID:3181353

  15. Principles of connectivity among morphologically defined cell types in adult neocortex.

    PubMed

    Jiang, Xiaolong; Shen, Shan; Cadwell, Cathryn R; Berens, Philipp; Sinz, Fabian; Ecker, Alexander S; Patel, Saumil; Tolias, Andreas S

    2015-11-27

    Since the work of Ramón y Cajal in the late 19th and early 20th centuries, neuroscientists have speculated that a complete understanding of neuronal cell types and their connections is key to explaining complex brain functions. However, a complete census of the constituent cell types and their wiring diagram in mature neocortex remains elusive. By combining octuple whole-cell recordings with an optimized avidin-biotin-peroxidase staining technique, we carried out a morphological and electrophysiological census of neuronal types in layers 1, 2/3, and 5 of mature neocortex and mapped the connectivity between more than 11,000 pairs of identified neurons. We categorized 15 types of interneurons, and each exhibited a characteristic pattern of connectivity with other interneuron types and pyramidal cells. The essential connectivity structure of the neocortical microcircuit could be captured by only a few connectivity motifs. PMID:26612957

  16. Escalating dose-multiple binge methamphetamine exposure results in degeneration of the neocortex and limbic system in the rat.

    PubMed

    Kuczenski, Ronald; Everall, Ian P; Crews, Leslie; Adame, Anthony; Grant, Igor; Masliah, Eliezer

    2007-09-01

    Abuse of stimulant drugs such as methamphetamine (METH) and cocaine has been associated with long-lasting persistent behavioral alterations. Although METH-induced changes in the striatal dopaminergic system might play a role in these effects, the potential underlying neuroanatomical substrate for the chronic cognitive dysfunction in METH users is unclear. To investigate the involvement of non-dopaminergic systems in the neurotoxic effects of METH, we treated rats with an escalating dose-multiple binge regimen, which we have suggested may more closely simulate human METH exposure profiles. Combined neuropathological and stereological analyses showed that 30 days after the last binge, there was shrinkage and degeneration in the pyramidal cell layers of the frontal cortex and in the hippocampal CA3 region. Further immunocytochemical analysis showed that METH exposure resulted in loss of calbindin interneurons in the neocortex and selective damage to pyramidal neurons in the CA3 region of the hippocampus and granular cells in the dentate gyrus that was accompanied by microglial activation. Taken together, these studies suggest that selective degeneration of pyramidal neurons and interneurons in the neocortex and limbic system might be involved in the cognitive alterations in METH users. PMID:17603040

  17. [Reactions of neural elements of neocortex on action of hypoxia at the early neonatal period in rats].

    PubMed

    Otellin, V A; Khozhai, L I; Shishko, T T

    2014-01-01

    In this work we studied reactions of neural elements of various neocortex areas (sensomotor, visual, auditory) on action of acute normobaric hypoxia. The study is performed on the model of human premature pregnancy (action of normobaric hypoxia on rat pups at the 2nd postnatal day). There are revealed monotypical and monodirected structural reconstructions in all studied neocortex parts. The chosen parameters of hypoxic action initiate several direct reactions as early as at the next day: a decrease in sizes of cell bodies and in volume of the cytoplasm, as well as an enhancement, as compared with control, of the apoptotic cell death. By the end of the neonatal period (5 days), several ultrastructural alterations indicating deceleration of processes of differentiation of nerve cells are revealed: arrest of processes of complication of smooth and rough endoplasmic reticulum and of Golgi apparatus, a small number of single ribosomes and polysomes in the cytoplasm, a decrease of the number of growth cones of axons and dendrites in neuropil, delay and disturbance of myelination processes in nerve fibers. The detected morphofunctional reconstructions can serve the structural ground for development of neonatal encephalopathies. PMID:25486820

  18. [Reactions of neural elements of neocortex on action of hypoxia at the early neonatal period in rats].

    PubMed

    2014-01-01

    In this work we studied reactions of neural elements of various neocortex areas (sensomotor, visual, auditory) on action of acute normobaric hypoxia. The study is performed on the model of human premature pregnancy (action of normobaric hypoxia on rat pups at the 2nd postnatal day). There are revealed monotypical and monodirected structural reconstructions in all studied neocortex parts. The chosen parameters of hypoxic action initiate several direct reactions as early as at the next day: a decrease in sizes of cell bodies and in volume of the cytoplasm, as well as an enhancement, as compared with control, of the apoptotic cell death. By the end of the neonatal period (5 days), several ultrastructural alterations indicating deceleration of processes of differentiation of nerve cells are revealed: arrest of processes of complication of smooth and rough endoplasmic reticulum and of Golgi apparatus, a small number of single ribosomes and polysomes in the cytoplasm, a decrease of the number of growth cones of axons and dendrites in neuropil, delay and disturbance of myelination processes in nerve fibers. The detected morphofunctional reconstructions can serve the structural ground for development of neonatal encephalopathies. PMID:25508951

  19. [A comparative analysis of restoration of electroencephalographic and protein-synthesizing activities in neocortex and hippocampus in hibernating (ground squirrels) and nonhibernating (rats) animals during exit from hypothermia].

    PubMed

    Ignat'ev, D A; Gordon, R Ia; Vorob'ev, V V; Rogachevskiĭ, V V

    2005-01-01

    A similarity in the sequence of restoration of the EEG spectrum between ground squirrels arousing from torpor and rats passing out of artificial hypothermia (17-18 degrees C) was shown. First of all, the low-frequency part of the EEG spectrum was restored. As animals warmed up, their breathing became hurried, cold shivering appeared, and the theta- and alpha-rhythms increased. During the exit from hypothermia, the activity of the protein-synthesizing system in both rats and ground squirrels was almost entirely restored when the animal body temperature achieved 21-22 degrees C. In ground squirrel, the rate of protein synthesis in the neocortex was lower than in hippocampus CA1 and CA3 areas, whereas in rats, on the contrary, it was higher in the neocortex in comparison with the CA3 area. PMID:15759514

  20. Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability

    PubMed Central

    Mehan, Neal D.; Strauss, Kenneth I.

    2012-01-01

    This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12–16 weeks) and juveniles (5– 6 weeks). Motor coordination and certain cognitive deficits showed age-dependence both before and after injury. Brain proteins were analyzed using silver-stained two-dimensional electrophoresis gels. Spot volume changes (>2-fold change, p<0.01) were identified between age and injury groups using computer-assisted densitometry. Sequences were determined by mass spectrometry of tryptic peptides. The 19 spots identified represented 13 different genes that fell into 4 general age- and injury-dependent expression patterns. Fifteen isoforms changed differentially with respect to both age and injury (p<0.05). Further investigations into the nature and function of these isoforms may yield insights into the vulnerability of older patients and resilience of younger patients in recovery after brain injuries. PMID:22088680

  1. Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability.

    PubMed

    Mehan, Neal D; Strauss, Kenneth I

    2012-09-01

    This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12-16 weeks) and juveniles (5-6 weeks). Motor coordination and certain cognitive deficits showed age-dependence both before and after injury. Brain proteins were analyzed using silver-stained two-dimensional electrophoresis gels. Spot volume changes (>2-fold change, p<0.01) were identified between age and injury groups using computer-assisted densitometry. Sequences were determined by mass spectrometry of tryptic peptides. The 19 spots identified represented 13 different genes that fell into 4 general age- and injury-dependent expression patterns. Fifteen isoforms changed differentially with respect to both age and injury (p<0.05). Further investigations into the nature and function of these isoforms may yield insights into the vulnerability of older patients and resilience of younger patients in recovery after brain injuries. PMID:22088680

  2. Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex.

    PubMed

    Thomson, A M; West, D C; Hahn, J; Deuchars, J

    1996-10-01

    1. Using dual intracellular recordings in slices of adult rat neocortex, twenty-four IPSPs activated by single presynaptic interneurones were studied in simultaneously recorded pyramidal cells. Fast spiking interneurones inhibited one in four or five of their close pyramidal neighbours. No reciprocal connections were observed. After recordings neurones were filled with biocytin. 2. Interneurones that elicited IPSPs were classified as classical fast spiking (n = 10), as non-classical fast spiking (n = 3, including one burst-firing interneurone), as unclassified, or slow interneurones (n = 8), or as regular spiking interneurones (n = 3), i.e. interneurones whose electrophysiological characteristics were indistinguishable from those of pyramidal cells. 3. All of the seven classical fast spiking cells anatomically fully recovered had aspiny, beaded dendrites. Their partially myelinated axons ramified extensively, varying widely in shape and extent, but randomly selected labelled axon terminals typically innervated somata and large calibre dendrites on electron microscopic examination. One 'autapse' was demonstrated. One presumptive regular spiking interneurone axon made four somatic and five dendritic connections with unlabelled targets. 4. Full anatomical reconstructions of labelled classical fast spiking interneurones and their postsynaptic pyramids (n = 5) demonstrated one to five boutons per connection. The two recorded IPSPs that were fully reconstructed morphologically (3 and 5 terminals) were, however, amongst the smallest recorded (< 0.4 mV). Some connections may therefore involve larger numbers of contacts. 5. Single axon IPSPs were between 0.2 and 3.5 mV in average amplitude at -55 to -60 mV. Extrapolated reversal potentials were between -70 and -82 mV. IPSP time course correlated with the type of presynaptic interneurone, but not with IPSP latency, amplitude, reversal potential, or sensitivity to current injected at the soma. 6. Classical fast spiking

  3. Pharmacological profiles of presynaptic nociceptin/orphanin FQ receptors modulating 5-hydroxytryptamine and noradrenaline release in the rat neocortex

    PubMed Central

    Marti, Matteo; Stocchi, Sara; Paganini, Francesca; Mela, Flora; Risi, Carmela De; Calo', Girolamo; Guerrini, Remo; Barnes, Timothy A; Lambert, David G; Beani, Lorenzo; Bianchi, Clementina; Morari, Michele

    2003-01-01

    The pharmacological profiles of presynaptic nociceptin/orphanin FQ (N/OFQ) peptide receptors (NOP) modulating 5-hydroxytryptamine (5-HT) and noradrenaline (NE) release in the rat neocortex were characterized in a preparation of superfused synaptosomes challenged with 10 mM KCl. N/OFQ concentration-dependently inhibited K+-evoked [3H]-5-HT and [3H]-NE overflow with similar potency (pEC50 ∼7.9 and ∼7.7, respectively) and efficacy (maximal inhibition ∼40%). N/OFQ (0.1 μM) inhibition of [3H]-5-HT and [3H]-NE overflow was antagonized by selective NOP receptor antagonists of peptide ([Nphe1]N/OFQ(1-13)NH2 and UFP-101; 10 and 1 μM, respectively) and non-peptide (J-113397 and JTC-801; both 0.1 μM) nature. Antagonists were routinely applied 3 min before N/OFQ. However, a 21 min pre-application time was necessary for J-113397 and JTC-801 to prevent N/OFQ inhibition of [3H]-NE overflow. The NOP receptor ligand [Phe1ψ(CH2-NH)Gly2]N/OFQ(1-13)NH2 ([F/G]N/OFQ(1-13)NH2; 3 μM) did not affect K+-evoked [3H]-NE but inhibited K+-evoked [3H]-5-HT overflow in a UFP-101 sensitive manner. [F/G]N/OFQ(1-13)NH2 antagonized N/OFQ actions on both neurotransmitters. The time-dependency of JTC-801 action was studied in CHO cells expressing human NOP receptors. N/OFQ inhibited forskolin-stimulated cAMP accumulation and JTC-801, tested at different concentrations (0.1–10 μM) and pre-incubation times (0, 40 and 90 min), antagonized this effect in a time-dependent manner. The Schild-type analysis excluded a competitive type of antagonism. We conclude that presynaptic NO receptors inhibiting 5-HT and NE release in the rat neocortex have similar pharmacological profiles. Nevertheless, they can be differentiated pharmacologically on the basis of responsiveness to [F/G]N/OFQ(1-13)NH2 and time-dependent sensitivity towards non-peptide antagonists. PMID:12522077

  4. Transmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineuronal activity in the treated area.

    PubMed

    Ludvig, Nandor; Tang, Hai M; Artan, N Sertac; Mirowski, Piotr; Medveczky, Geza; Baptiste, Shirn L; Darisi, Sindhu; Kuzniecky, Ruben I; Devinsky, Orrin; French, Jacqueline A

    2011-04-18

    Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and muscimol pretreatment in the concentration range of 0.005-0.05 mM did not prevent EEG seizures. In contrast, 0.5-mM muscimol reduced the average EEG Seizure Duration Ratio value from 0.30±0.04 to 0. At this muscimol concentration, the average baseline multineuronal firing rate of 10.9±4.4 spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0±1.8 to 3.7±0.9 spikes/s in the last 10 min of pretreatment. These data indicate that transmeningeal muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions. PMID:21338591

  5. Spontaneous epileptiform activity in rat neocortex after controlled cortical impact injury.

    PubMed

    Yang, Lie; Afroz, Sonia; Michelson, Hillary B; Goodman, Jeffrey H; Valsamis, Helen A; Ling, Douglas S F

    2010-08-01

    A hallmark of severe traumatic brain injury (TBI) is the development of post-traumatic epilepsy (PTE). However, the mechanisms underlying PTE remain poorly understood. In this study, we used a controlled cortical impact (CCI) model in rats to examine post-traumatic changes in neocortical excitability. Neocortical slices were prepared from rats at 7-9 days (week 1) and 14-16 days (week 2) after CCI injury. By week 2, we observed a substantial gray matter lesion with a cavity that extended to the hippocampal structure. Fluoro-Jade B staining of slices revealed active neuronal degeneration during weeks 1 and 2. Intracellular and extracellular recordings obtained from layer V revealed evoked and spontaneous epileptiform discharges in neocortices of CCI-injured rats. At week 1, intracellular recordings from pyramidal cells revealed evoked epileptiform firing that was synchronized with population events recorded extracellularly, suggestive of increased excitability. This activity was characterized by bursts of action potentials that were followed by recurrent, repetitive after-discharges. At week 2, both spontaneous and evoked epileptiform firing were recorded in slices from injured rats. The evoked discharges resembled those observed at week 1, but with longer burst durations. Spontaneous activity included prolonged, ictal-like discharges lasting up to 8-10 sec, and briefer interictal-like burst events (<1 sec). These results indicate that during the first 2 weeks following severe CCI injury, there is a progressive development of neocortical hyperexcitability that ultimately leads to spontaneous epileptiform firing, suggesting a rapid epileptogenic process. PMID:20504156

  6. Effects of Gamma Hydroxybutyric Acid on Inhibition and Excitation in Rat Neocortex

    PubMed Central

    Li, Qiang; Kuhn, Cynthia M.; Wilson, Wilkie A.; Lewis, Darrell V.

    2008-01-01

    The mechanism by which the sedative and amnestic recreational drug gamma hydroxybutyric acid (GHB) acts is controversial. Some studies indicate that it acts at its unique receptor, while others demonstrate effects mediated through the GABAB receptor. We examined the effect of GHB on evoked GABAA receptor mediated mono- and polysynaptic IPSCs as well as on NMDA and AMPA mediated EPSCs in layers II/III pyramidal cells of the frontal cortex of rat brain. One millimolar (mM) GHB suppressed monosynaptic IPSCs by 20%, whereas polysynaptic IPSCs were reduced by 56%. GHB (1mM) also produced a significant suppression of NMDA-mediated EPSCs by 53% compared to 27% suppression of AMPA-mediated EPSCs. All effects of GHB on IPSCs and EPSCs were reversed by the specific GABAB antagonist CGP62349, but not by the GHB receptor antagonist NCS 382. Consistent with a presynaptic site of action, GHB reduced the frequency but not the amplitude of AMPA receptor mediated mEPSCs and had no effect on postsynaptic currents evoked by direct application of NMDA. Finally, even though GHB appeared to be acting at presynaptic GABAB receptors, GHB and the GABAB agonist baclofen appeared to have opposite potencies for depression of NMDA vs AMPA mediated EPSCs. GHB showed a preference for depressing NMDA responses while baclofen more potently suppressed AMPA responses. The suppression of NMDA more than AMPA responses by GHB at intoxicating doses may make it attractive as a recreational drug and may explain why GHB is abused and baclofen is not. PMID:17904295

  7. Separate activation of fast and slow inhibitory postsynaptic potentials in rat neocortex in vitro.

    PubMed Central

    Benardo, L S

    1994-01-01

    Synaptic inhibition was investigated by stimulating inhibitory neurones with focal microapplications of glutamate, while recording from layer V pyramidal neurones of rat somatosensory cortical slices. One class of inhibitory postsynaptic potentials (IPSPs) thus elicited was characterized as a fast, chloride-mediated, GABAA IPSP in part by its fast time-to-peak (mean 2.5 ms) and brief duration, but primarily on the basis of its reversal potential at -68 mV, and its blockade by picrotoxin. The average peak amplitude for these fast IPSPs was -1.5 mV, measured at -60 mV. The peak conductance calculated for these events was about 10 nS. The conductance change associated with the maximal fast inhibitory postsynaptic potential resulting from electrical stimulation of afferent pathways ranged up to 116 nS. A second class of IPSP was encountered much less frequently. These glutamate-triggered events were characterized as slow, potassium-mediated GABAB IPSPs partly because of their longer times-to-peak (mean, 45 ms) and duration, but especially because of their extrapolated equilibrium potential at about -89 mV and blockade by 2-hydroxysaclofen. The average peak amplitude for these slow IPSPs was -2.3 mV, measured at -60 mV. The peak conductance for these events was about 8 nS. IPSPs resulting from the excitation of individual inhibitory interneurones were elicited by glutamate microapplication at particular locations relative to recording sites. Both fast and slow IPSPs were generated, but these occurred as separate events, and mixed responses were never seen. Thus, the two mechanistically distinct types of IPSPs which result from GABA interaction at GABAA and GABAB receptors on neocortical neurones may be mediated by separate classes of inhibitory neurones. PMID:7913968

  8. Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

    PubMed Central

    Martínez-Cerdeño, Verónica; Noctor, Stephen C.; Espinosa, Ana; Ariza, Jeanelle; Parker, Philip; Orasji, Samantha; Daadi, Marcel M.; Bankiewicz, Krystof; Alvarez-Buylla, Arturo; Kriegstein, Arnold R.

    2014-01-01

    SUMMARY We investigated a strategy to ameliorate the motor symptoms of rats that received 6-hydroxydopamine (6-OHDA) lesions, a rodent model of Parkinson’s disease, through transplantation of embryonic medial ganglionic eminence (MGE) cells into the striatum. During brain development, embryonic MGE cells migrate into the striatum and neocortex where they mature into GABAergic interneurons and play a key role in establishing the balance between excitation and inhibition. Unlike most other embryonic neurons, MGE cells retain the capacity for migration and integration when transplanted into the postnatal and adult brain. We performed MGE cell transplantation into the basal ganglia of control and 6-OHDA-lesioned rats. Transplanted MGE cells survived, differentiated into GABA+ neurons, integrated into host circuitry, and modifed motor behavior in both lesioned and control rats. Our data suggest that MGE cell transplantation into the striatum is a promising approach to investigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases. PMID:20207227

  9. The use of microwave tissue fixation to demonstrate the in vivo phosphorylation of an acidic 80,000 molecular weight protein in the rat neocortex following treatment with soman

    SciTech Connect

    Mobley, P.L.; Gonzalez, N.E. )

    1991-01-01

    Studies were conducted to determine if soman, a cholinesterase inhibitor, could activate the protein kinase C system in the rat neocortex. Using microwave radiation for rapid tissue fixation, it was demonstrated that treatment with soman increased {sup 32}P incorporation into an acidic 80,000 molecular weight, heat-stable protein in vivo. Based on relative molecular weight and isoelectric point this protein appears to be identical to a protein identified as a substrate for protein kinase C. Additionally, a protein of the same molecular weight and isoelectric point could be phosphorylated in tissue slices prepared from the neocortex by cholinergic dependent mechanisms. Also, treatment with soman decreased protein kinase C in the soluble fraction of this brain region; however, no corresponding increase was observed in the particulate fraction. These results suggest that soman can activate protein kinase C in vivo, and demonstrate the utility of using microwave tissue fixation to study protein phosphorylation events in vivo.

  10. Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats.

    PubMed

    Malkin, Sergey L; Amakhin, Dmitry V; Veniaminova, Ekaterina A; Kim, Kira Kh; Zubareva, Olga E; Magazanik, Lev G; Zaitsev, Aleksey V

    2016-07-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study. The changes in AMPA receptor subunit composition were investigated in several brain areas, including the medial prefrontal cortex (mPFC), the temporal cortex (TC), and the dorsal (DH) and ventral hippocampus (VH) during the first week following pilocarpine-induced status epilepticus (PILO-induced SE). In the hippocampus, GluA1 and GluA2 mRNA expression slightly decreased after PILO-induced SE and returned to the initial level on the seventh day. We did not detect any significant changes in mRNA expression of the GluA1 and GluA2 subunits in the TC, whereas in the mPFC we observed a significant increase of GluA1 mRNA expression on the third day and a decrease in GluA2 mRNA expression during the entire first week. Accordingly, the GluA1/GluA2 expression ratio increased in the mPFC, and the functional properties of the pyramidal cell excitatory synapses were disturbed. Using whole-cell voltage-clamp recordings, we found that on the third day following PILO-induced SE, isolated mPFC pyramidal neurons showed an inwardly rectifying current-voltage relation of kainate-evoked currents, suggesting the presence of GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). IEM-1460, a selective antagonist of CP-AMPARs, significantly reduced the amplitude of evoked EPSC in pyramidal neurons from mPFC slices on the first and third days, but not on the seventh day. The antagonist had no effects on EPSC amplitude in slices from control animals. Thus, our data demonstrate that PILO-induced SE affects subunit composition of AMPARs in different brain areas, including the mPFC. SE induces transient (up to few days) incorporation of CP-AMPARs in the excitatory synapses of mPFC pyramidal neurons, which may disrupt normal circuitry functions. PMID:27109923

  11. Persistent neocortical astrogliosis in adult wistar rats following prenatal ethanol exposure.

    PubMed

    Fakoya, Francis Adelade

    2005-06-01

    Timed pregnant wistar rats were divided randomly into groups A and B (n=6) each and C (n=4). Group A received a daily ethanol dose of 5.8 g/kg body weight per day, at 16.00 h on days 9-12th of gestation by intragastric intubations. Group B was pair-fed along with the treated rats and received an isocaloric solution of sucrose to substitute for the ethanol in the experimental group, for the same duration, while group C received standard chow and water ad libitum. The adult offsprings at 42 days of age, (n=10) from each group were sacrificed by whole body perfusion-fixation, after anaesthesia by an overdose of pentothal intraperitoneally. Specimens of neocortical samples were processed routinely for paraffin embedding and sections of 6 microm thickness stained for neurohistology. Another set of specimens was cryosectioned at -23 degrees C after cryoprotection in 30% sucrose/PBS and evaluated for GFAP immunohistochemistry. The study showed a distortion of the microanatomy of the neocortex in the treatment group A, particularly of layer V pyramidal neurons, which revealed mostly pyknotic pyramidal neurons with broken dendrites, collapsed cell bodies, obliterated nuclei and nucleoli. No differences were found between the brains from rats in groups B and C. There were widespread focal areas of reactive astrogliosis, more prominent within the layer V. Astrocytes demonstrated highly stained GFAP-positive immunoreactivity with heavy fibrillary processes in the neocortex of group A offsprings compared to the controls. The sub-pial regions were, however, sparse. In conclusion, this study confirms the hypothesis that microanatomical and microchemical changes following prenatal ethanol exposure persist into adulthood in rats. PMID:15862187

  12. Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

    PubMed

    Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

    2016-07-01

    Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction. PMID:25678360

  13. Cooling produces minimal neuropathology in neocortex and hippocampus.

    PubMed

    Yang, Xiao-Feng; Kennedy, Bryan R; Lomber, Stephen G; Schmidt, Robert E; Rothman, Steven M

    2006-09-01

    Cooling is a potential treatment for several neurological diseases. We have examined rodent and cat neocortex, cooled to 5 and 3 degrees C, respectively, to identify a lower limit for safely cooling brain. Rat neocortex, intermittently cooled with a thermoelectric device for 2 h, showed no signs of neuronal injury after cresyl violet or TUNEL staining. Neurons were also preserved in cat cortex cooled for up to 2 h daily for 10 months. Cooled rat and cat cortex showed glial proliferation, but this was also observed in sham-operated rat cortex. When hippocampal slices from mice expressing the Green Fluorescent Protein (GFP) in neurons were cooled to 5 degrees C, but not higher temperatures, we saw reversible dendritic beading and spine loss after 15-30 min. While there may be biochemical and functional alterations in brain cooled as low as 5 degrees C, the neuropathological consequences of brain cooling appear to be insignificant. PMID:16828292

  14. Quantitative relationships in delphinid neocortex

    PubMed Central

    Mortensen, Heidi S.; Pakkenberg, Bente; Dam, Maria; Dietz, Rune; Sonne, Christian; Mikkelsen, Bjarni; Eriksen, Nina

    2014-01-01

    Possessing large brains and complex behavioral patterns, cetaceans are believed to be highly intelligent. Their brains, which are the largest in the Animal Kingdom and have enormous gyrification compared with terrestrial mammals, have long been of scientific interest. Few studies, however, report total number of brain cells in cetaceans, and even fewer have used unbiased counting methods. In this study, using stereological methods, we estimated the total number of cells in the neocortex of the long-finned pilot whale (Globicephala melas) brain. For the first time, we show that a species of dolphin has more neocortical neurons than any mammal studied to date including humans. These cell numbers are compared across various mammals with different brain sizes, and the function of possessing many neurons is discussed. We found that the long-finned pilot whale neocortex has approximately 37.2 × 109 neurons, which is almost twice as many as humans, and 127 × 109 glial cells. Thus, the absolute number of neurons in the human neocortex is not correlated with the superior cognitive abilities of humans (at least compared to cetaceans) as has previously been hypothesized. However, as neuron density in long-finned pilot whales is lower than that in humans, their higher cell number appears to be due to their larger brain. Accordingly, our findings make an important contribution to the ongoing debate over quantitative relationships in the mammalian brain. PMID:25505387

  15. Quantitative relationships in delphinid neocortex.

    PubMed

    Mortensen, Heidi S; Pakkenberg, Bente; Dam, Maria; Dietz, Rune; Sonne, Christian; Mikkelsen, Bjarni; Eriksen, Nina

    2014-01-01

    Possessing large brains and complex behavioral patterns, cetaceans are believed to be highly intelligent. Their brains, which are the largest in the Animal Kingdom and have enormous gyrification compared with terrestrial mammals, have long been of scientific interest. Few studies, however, report total number of brain cells in cetaceans, and even fewer have used unbiased counting methods. In this study, using stereological methods, we estimated the total number of cells in the neocortex of the long-finned pilot whale (Globicephala melas) brain. For the first time, we show that a species of dolphin has more neocortical neurons than any mammal studied to date including humans. These cell numbers are compared across various mammals with different brain sizes, and the function of possessing many neurons is discussed. We found that the long-finned pilot whale neocortex has approximately 37.2 × 10(9) neurons, which is almost twice as many as humans, and 127 × 10(9) glial cells. Thus, the absolute number of neurons in the human neocortex is not correlated with the superior cognitive abilities of humans (at least compared to cetaceans) as has previously been hypothesized. However, as neuron density in long-finned pilot whales is lower than that in humans, their higher cell number appears to be due to their larger brain. Accordingly, our findings make an important contribution to the ongoing debate over quantitative relationships in the mammalian brain. PMID:25505387

  16. Neocortical neurodegeneration in young adult Wistar rats prenatally exposed to ethanol.

    PubMed

    Fakoya, Francis Adelade; Caxton-Martins, Ezekiel Ademola

    2006-01-01

    This study was aimed to determine the persistence of neurodegeneration in the cerebral cortex of adult Wistar rats following prenatal ethanol exposure. Timed pregnant rats maintained on standard mouse chow (Ladokun Feeds, Ibadan, Nigeria) and water ad libitum were used for the study. The rats were divided randomly into groups A and B (n-6) and C (n = 4). Group A received a daily ethanol dose of 5.8 g/Kg body weight/day, on the 9th, 10th, 11th, and 12th days of gestation by intragastric intubation, at 16.00 h (PEE) group B was pair-fed with the ethanol dams on isocaloric solution of sucrose for the same duration (PF), while group C received standard chow (C) and water ad libitum. At birth, the pups were weighed and weaned at 30 days of age. Wet brain weights of adult offsprings were determined at 42 days of age. Following whole body perfusion-fixation after anaesthesia, specimens of the neocortex were processed routinely for paraffin embedding and sections of 6 mum thickness stained for neurohistology from each group. Another set of specimens was cryosectioned at -23 degrees C and evaluated for apoptosis by the TUNEL method. The study showed a significantly sustained 44% reduction in brain weight. Neurodegeneration was evident in the layer V, consisting of mostly pyknotic pyramidal neurons, with broken dendrites, collapsed cell bodies, obliterated nuclei and nucleoli. There was a 55% decrease in the normal pyramidal neuron cell pack density. The negative TUNEL signals in both groups suggest that apoptosis may play no role in the mechanism of action occurring at this age of the animals. These sustained changes may underlie the neurobehavioural deficits that have been variously reported. PMID:16503114

  17. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  18. Interactions between respiratory oscillators in adult rats.

    PubMed

    Huckstepp, Robert Tr; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. PMID:27300271

  19. Electrotonic Coupling between Pyramidal Neurons in the Neocortex

    PubMed Central

    Wang, Yun; Barakat, Amey; Zhou, Hongwei

    2010-01-01

    Electrotonic couplings (i.e., electrical synapses or gap junctions) are fundamental to neuronal synchronization, and thus essential for many physiological functions and pathological disorders. Interneuron electrical synapses have been studied intensively. Although studies on electrotonic couplings between pyramidal cells (PCs) are emerging, particularly in the hippocampus, evidence is still rare in the neocortex. The electrotonic coupling of PCs in the neocortex is therefore largely unknown in terms of electrophysiological, anatomical and synaptological properties. Using multiple patch-clamp recording with differential interference contrast infrared videomicroscopy (IR-DIC) visualization, histochemical staining, and 3D-computer reconstruction, electrotonic coupling was recorded between close PCs, mainly in the medial prefrontal cortex as well as in the visual cortical regions of ferrets and rats. Compared with interneuron gap junctions, these electrotonic couplings were characterized by several special features. The recording probability of an electrotonic coupling between PCs is extremely low; but the junctional conductance is notably high, permitting the direct transmission of action potentials (APs) and even tonic firing between coupled neurons. AP firing is therefore perfectly synchronized between coupled PCs; Postjunctional APs and spikelets alternate following slight changes of membrane potentials; Postjunctional spikelets, especially at high frequencies, are summated and ultimately reach AP-threshold to fire. These properties of pyramidal electrotonic couplings largely fill the needs, as predicted by simulation studies, for the synchronization of a neuronal assembly. It is therefore suggested that the electrotonic coupling of PCs plays a unique role in the generation of neuronal synchronization in the neocortex. PMID:20436674

  20. Long-term tracing of the BrdU label-retaining cells in adult rat brain.

    PubMed

    Zhang, Lei; Li, Haihong; Zeng, Shaopeng; Chen, Lu; Fang, Zeman; Huang, Qingjun

    2015-03-30

    Stem cells have been shown to be label-retaining, slow-cycling cells. In the adult mammalian central nervous system, the distribution of the stem cells is inconsistent among previous studies. The purpose of the present study was to determine the distribution of BrdU-LRCs and the cell types of the BrdU-LRCs in rat brain. To label BrdU-LRCs in rat brain, six newborn rats were administered intraperitoneal injections of BrdU 50mg/kg/time twice a day at 2h intervals, over four consecutive days. The BrdU-LRCs were detected by immunohistochemistry, the cell types were examined by double immunofluorescence staining for BrdU/GFAP and BrdU/MAP2, and the percentage of BrdU-LRCs was calculated following a chase period of 24 weeks post-injection. We observed that BrdU-LRCs distributed extensively in rat brain. In the LV, DG, striatum, cerebellum and neocortex, the percentage of BrdU-LRCs was 11.3 ± 2.5%, 10.9 ± 1.3%, 6.4 ± 1.2%, 5.6 ± 0.8%, and 4.9 ± 0.6%, respectively. The highest density of BrdU-LRCs was in LV and DG, the known stem cell sites in adult mammalian brain. Both BrdU/GFAP and BrdU/MAP2 double-staining cells could be detected in the above five brain subregions. Ongoing cell production was widespread in the adult mammalian brain, which would allow us to reevaluate the capacity and potentiality of the brain in homeostasis, wound repair, and regeneration. PMID:25681624

  1. Embedding a Panoramic Representation of Infrared Light in the Adult Rat Somatosensory Cortex through a Sensory Neuroprosthesis.

    PubMed

    Hartmann, Konstantin; Thomson, Eric E; Zea, Ivan; Yun, Richy; Mullen, Peter; Canarick, Jay; Huh, Albert; Nicolelis, Miguel A L

    2016-02-24

    Can the adult brain assimilate a novel, topographically organized, sensory modality into its perceptual repertoire? To test this, we implemented a microstimulation-based neuroprosthesis that rats used to discriminate among infrared (IR) light sources. This system continuously relayed information from four IR sensors that were distributed to provide a panoramic view of IR sources, into primary somatosensory cortex (S1). Rats learned to discriminate the location of IR sources in <4 d. Animals in which IR information was delivered in spatial register with whisker topography learned the task more quickly. Further, in animals that had learned to use the prosthesis, altering the topographic mapping from IR sensor to stimulating electrode had immediate deleterious effects on discrimination performance. Multielectrode recordings revealed that S1 neurons had multimodal (tactile/IR) receptive fields, with clear preferences for those stimuli most likely to be delivered during the task. Neuronal populations predicted, with high accuracy, which stimulation pattern was present in small (75 ms) time windows. Surprisingly, when identical microstimulation patterns were delivered during an unrelated task, cortical activity in S1 was strongly suppressed. Overall, these results show that the adult mammalian neocortex can readily absorb completely new information sources into its representational repertoire, and use this information in the production of adaptive behaviors. PMID:26911689

  2. Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats.

    PubMed

    Navarro, Daniela; Alvarado, Mayvi; Navarrete, Francisco; Giner, Manuel; Obregon, Maria Jesus; Manzanares, Jorge; Berbel, Pere

    2015-01-01

    Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distribution of vesicular glutamate transporter-1 (VGluT1; glutamatergic) and vesicular inhibitory amino acid transporter (VGAT; GABAergic) immunoreactive (ir) boutons in the hippocampus and somatosensory cortex, and the behavior of the pups. Hypothyroidism was induced by adding 0.02% methimazole (MMI) and 1% KClO4 to the drinking water starting at embryonic day 10 (E10; developmental hypothyroidism) and E21 (early postnatal hypothyroidism) until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhibition (somatosensory attention) and the elevated plus-maze (anxiety-like assessment) tests. The distribution, density and size of VGluT1-ir and VGAT-ir boutons in the hippocampus and somatosensory cortex was abnormal in MMI pups and these changes correlate with behavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, both developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic boutons in dentate gyrus leading to an abnormal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter behavior in rats. Our data show cytoarchitectonic alterations in the basic excitatory hippocampal loop, and in local inhibitory circuits of the somatosensory cortex and hippocampus that might contribute to the delayed neurocognitive outcome observed in thyroid hormone deficient children born in iodine deficient areas, or suffering from congenital hypothyroidism. PMID:25741243

  3. Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

    PubMed Central

    Navarro, Daniela; Alvarado, Mayvi; Navarrete, Francisco; Giner, Manuel; Obregon, Maria Jesus; Manzanares, Jorge; Berbel, Pere

    2015-01-01

    Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distribution of vesicular glutamate transporter-1 (VGluT1; glutamatergic) and vesicular inhibitory amino acid transporter (VGAT; GABAergic) immunoreactive (ir) boutons in the hippocampus and somatosensory cortex, and the behavior of the pups. Hypothyroidism was induced by adding 0.02% methimazole (MMI) and 1% KClO4 to the drinking water starting at embryonic day 10 (E10; developmental hypothyroidism) and E21 (early postnatal hypothyroidism) until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhibition (somatosensory attention) and the elevated plus-maze (anxiety-like assessment) tests. The distribution, density and size of VGluT1-ir and VGAT-ir boutons in the hippocampus and somatosensory cortex was abnormal in MMI pups and these changes correlate with behavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, both developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic boutons in dentate gyrus leading to an abnormal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter behavior in rats. Our data show cytoarchitectonic alterations in the basic excitatory hippocampal loop, and in local inhibitory circuits of the somatosensory cortex and hippocampus that might contribute to the delayed neurocognitive outcome observed in thyroid hormone deficient children born in iodine deficient areas, or suffering from congenital hypothyroidism. PMID:25741243

  4. Empirical assessment of synapse numbers in primate neocortex.

    PubMed

    Mouton, P R; Price, D L; Walker, L C

    1997-08-22

    Reliable methods are needed to assess the impact of synaptic loss on brain function. In this empirical study we demonstrate a novel and efficient method using immunocytochemistry (ICC) and modern stereological techniques to quantify synapses in neocortex of adult primates (Macaca fascicularis). Systematic-uniform-random sections through forebrain from two 10-year-old monkeys were immunostained for estimation of synaptophysin-immunoreactive (synaptophysin-IR) presynaptic boutons (synapses). Adjacent sections were stained with cresyl violet for estimation of total number of neuronal cell bodies. The unbiased Cavalieri method was used to estimate total forebrain and neocortical volumes to a high level of precision (coefficient of error (CE) < or = 0.10)). Synapse-to-neuron ratios varied from 860 in frontal cortex to 2300 in parietal-temporal cortex. The combination of Cavalieri and optical disector methods provided a direct means of estimating approximately 1.25 trillion (x 10(12)) total synaptophysin-immunopositive boutons and approximately 1.01 billion (x 10(9)) cell bodies in neocortex, with low CEs (0.12). Time required to make precise estimates of total neocortical and forebrain volumes and total numbers of synapses and neurons in neocortex was approximately 2-3 h per case from stained sections. The approach is a direct and efficient technique to quantify total synapse and neuron numbers within a defined brain structure. PMID:9288643

  5. Development and Evolution of the Human Neocortex

    PubMed Central

    Lui, Jan H.; Hansen, David V.; Kriegstein, Arnold R.

    2013-01-01

    The size and surface area of the mammalian brain are thought to be critical determinants of intellectual ability. Recent studies show that development of the gyrated human neocortex involves a lineage of neural stem and transit-amplifying cells that forms the outer subventricular zone (OSVZ), a proliferative region outside the ventricular epithelium. We discuss how proliferation of cells within the OSVZ expands the neocortex by increasing neuron number and modifying the trajectory of migrating neurons. Relating these features to other mammalian species and known molecular regulators of the mouse neocortex suggests how this developmental process could have emerged in evolution. PMID:21729779

  6. Embedding a Panoramic Representation of Infrared Light in the Adult Rat Somatosensory Cortex through a Sensory Neuroprosthesis

    PubMed Central

    Hartmann, Konstantin; Thomson, Eric E.; Zea, Ivan; Yun, Richy; Mullen, Peter; Canarick, Jay; Huh, Albert

    2016-01-01

    Can the adult brain assimilate a novel, topographically organized, sensory modality into its perceptual repertoire? To test this, we implemented a microstimulation-based neuroprosthesis that rats used to discriminate among infrared (IR) light sources. This system continuously relayed information from four IR sensors that were distributed to provide a panoramic view of IR sources, into primary somatosensory cortex (S1). Rats learned to discriminate the location of IR sources in <4 d. Animals in which IR information was delivered in spatial register with whisker topography learned the task more quickly. Further, in animals that had learned to use the prosthesis, altering the topographic mapping from IR sensor to stimulating electrode had immediate deleterious effects on discrimination performance. Multielectrode recordings revealed that S1 neurons had multimodal (tactile/IR) receptive fields, with clear preferences for those stimuli most likely to be delivered during the task. Neuronal populations predicted, with high accuracy, which stimulation pattern was present in small (75 ms) time windows. Surprisingly, when identical microstimulation patterns were delivered during an unrelated task, cortical activity in S1 was strongly suppressed. Overall, these results show that the adult mammalian neocortex can readily absorb completely new information sources into its representational repertoire, and use this information in the production of adaptive behaviors. SIGNIFICANCE STATEMENT Understanding the potential for plasticity in the adult brain is a key goal for basic neuroscience and modern rehabilitative medicine. Our study examines one dimension of this challenge: how malleable is sensory processing in adult mammals? We implemented a panoramic infrared (IR) sensory prosthetic system in rats; it consisted of four IR sensors equally spaced around the circumference of the head of the rat. Each sensor was coupled to a microstimulating electrode placed in the somatosensory

  7. ACUTE BEHAVIORAL TOXICITY OF CARBARYL AND PROPOXUR IN ADULT RATS

    EPA Science Inventory

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8,...

  8. TRIMETHYLTIN DISRUPTS ACOUSTIC STARTLE RESPONDING IN ADULT RATS

    EPA Science Inventory

    Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, the authors examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N=12/dose) received a single i.p. injection o...

  9. Population dynamics during cell proliferation and neuronogenesis in the developing murine neocortex

    NASA Technical Reports Server (NTRS)

    Nowakowski, Richard S.; Caviness, Verne S Jr; Takahashi, Takao; Hayes, Nancy L.

    2002-01-01

    During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the "neuronogenetic interval" (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of the NI. The proportion of daughter cells that re-enter the cell cycle (P cells) changes in a complementary fashion from 1 at the onset of the NI to 0 at the end of the NI. This set of systematic changes in the cell cycle and the output from the proliferative population of the PVE allows a quantitative and mathematical treatment of the expansion of the PVE and the growth of the cortical plate that nicely accounts for the observed expansion and growth of the developing neocortex. In addition, we show that the cells produced during a 2-h window of development during specific cell cycles reside in a specific set of laminae in the adult cortex, but that the distributions of the output from consecutive cell cycles overlap. These dynamic events occur in all areas of the PVE underlying the neocortex, but there is a gradient of maturation that begins in the rostrolateral neocortex near the striatotelencephalic junction and which spreads across the surface of the neocortex over a period of 24-36 h. The

  10. A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis123

    PubMed Central

    Grigereit, Laura; Pickel, James

    2016-01-01

    Abstract The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID:27257630

  11. Physiological responses during whole body suspension of adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Fell, R. D.; Musacchia, X. J.

    1987-01-01

    The objective of this study was to characterize responses of adult rats to one and two weeks of whole body suspension. Body weights and food and water intakes were initially reduced during suspension, but, while intake of food and water returned to presuspension levels, body weight remained depressed. Diuresis was evident, but only during week two. Hindlimb muscle responses were differential, with the soleus exhibiting the greatest atrophy and the EDL a relative hypertrophy. These findings suggest that adult rats respond qualitatively in a manner similar to juveniles during suspension.

  12. Neocortex in early mammals and its subsequent variations

    PubMed Central

    Kaas, Jon H.

    2013-01-01

    Neocortex is an important part of the mammalian brain that is quite different from its homologue of the dorsal cortex in the reptilian brain. Whereas dorsal cortex is small, thin, and composed of a single layer of neurons, neocortex is thick and has six layers, while being variable across species in size, number of functional areas, and architectonic differentiation. Early mammals had little neocortex, with perhaps 20 areas of poor structural differentiation. Many extant mammals continue to have small brains with little neocortex, but they often have sensory specializations reflected in the organization of sensory areas in neocortex. In primates, neocortex is variously enlarged and characterized by structural and other specializations, including those of cortical networks devoted to vision and visuomotor processing.In humans, neocortex occupies 80% of the volume of the brain, where as many as 200 areas may exist. PMID:21534990

  13. Early life stress induces renal dysfunction in adult male rats but not female rats

    PubMed Central

    Loria, Analia S.; Yamamoto, Tatsuo; Pollock, Jennifer S.

    2013-01-01

    Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats. PMID:23174859

  14. DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats

    PubMed Central

    Lee, Heekyung; Kang, Eunchai; GoodSmith, Douglas; Yoon, Do Yeon; Song, Hongjun; Knierim, James J.; Ming, Guo-li; Christian, Kimberly M.

    2015-01-01

    Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. PMID:26161071

  15. DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats.

    PubMed

    Lee, Heekyung; Kang, Eunchai; GoodSmith, Douglas; Yoon, Do Yeon; Song, Hongjun; Knierim, James J; Ming, Guo-Li; Christian, Kimberly M

    2015-01-01

    Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. PMID:26161071

  16. ACUTE TOXICITY OF PESTICIDES IN ADULT AND WEANLING RATS

    EPA Science Inventory

    LD sub 50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and 4 test...

  17. High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

    PubMed Central

    Kong, Chae-Gwan; Kim, Man Soo; Park, Eun-Young

    2014-01-01

    Study Design In vitro cell culture. Purpose The purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells. Overview of Literature Diabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells. Methods Nucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified. Results Two high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner. Conclusions The results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus. PMID:25346805

  18. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  19. The cellular composition of the marsupial neocortex.

    PubMed

    Seelke, Adele M H; Dooley, James C; Krubitzer, Leah A

    2014-07-01

    In the current investigation we examined the number and proportion of neuronal and non-neuronal cells in the primary sensory areas of the neocortex of a South American marsupial, the short-tailed opossum (Monodelphis domestica). The primary somatosensory (S1), auditory (A1), and visual (V1) areas were dissected from the cortical sheet and compared with each other and the remaining neocortex using the isotropic fractionator technique. We found that although the overall sizes of V1, S1, A1, and the remaining cortical regions differed from each other, these divisions of the neocortex contained the same number of neurons, but the remaining cortex contained significantly more non-neurons than the primary sensory regions. In addition, the percent of neurons was higher in A1 than in the remaining cortex and the cortex as a whole. These results are similar to those seen in non-human primates. Furthermore, these results indicate that in some respects, such as number of neurons, the neocortex is homogenous across its extent, whereas in other aspects of organization, such as non-neuronal number and percentage of neurons, there is non-uniformity. Whereas the overall pattern of neuronal distribution is similar between short-tailed opossums and eutherian mammals, short-tailed opossum have a much lower cellular and neuronal density than other eutherian mammals. This suggests that the high neuronal density cortices of mammals such as rodents and primates may be a more recently evolved characteristic that is restricted to eutherians, and likely contributes to the complex behaviors we see in modern mammals. PMID:24414857

  20. TERMINAL ARBORS OF AXONS PROJECTING TO THE SOMATOSENSORY CORTEX OF THE ADULT RAT. 2. THE ALTERED MORPHOLOGY OF THALAMOCORTICAL AFFERENTS FOLLOWING NEONATAL INFRAORBITAL NERVE CUT (JOURNAL VERSION)

    EPA Science Inventory

    The organization of the whisker representation within the neocortex of the rat is dependent on an intact periphery during development. To further investigate how alterations in the cortical map arise the authors examined the organization of thalamocortical afferents to the whiske...

  1. Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats.

    PubMed

    Pilipović, Ivan; Vujnović, Ivana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Kosec, Duško; Stojić-Vukanić, Zorica; Leposavić, Gordana

    2016-08-15

    The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and β2- and α1-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average β2- and α1-AR thymocyte surface density changed in the opposite direction with age; the density of β2-AR decreased, whereas that of α1-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of β2-ARs, but it increased that of α1-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age- and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic

  2. BMP3 expression in the adult rat CNS.

    PubMed

    Yamashita, Kanna; Mikawa, Sumiko; Sato, Kohji

    2016-07-15

    Bone morphogenetic protein-3 (BMP3) is a very unique member of the TGF-β superfamily, because it functions as an antagonist to both the canonical BMP and activin pathways and plays important roles in multiple biological events. Although BMP3 expression has been described in the early development of the kidney, intestine and bone, little information is available for BMP3 expression in the central nervous system (CNS). We, thus, investigated BMP3 expression in the adult rat CNS using immunohistochemistry. BMP3 was intensely expressed in most neurons and their axons. Furthermore, we found that astrocytes and ependymal cells also express BMP3 protein. These data indicate that BMP3 is widely expressed throughout the adult CNS, and its abundant expression in the adult brain strongly supports the idea that BMP3 plays important roles in the adult brain. PMID:27130896

  3. Low doses of memantine disrupt memory in adult rats.

    PubMed

    Creeley, Catherine; Wozniak, David F; Labruyere, Joanne; Taylor, George T; Olney, John W

    2006-04-12

    Memantine, a drug recently approved for treatment of Alzheimer's disease, has been characterized as a unique NMDA antagonist that confers protection against excitotoxic neurodegeneration without the serious side effects that other NMDA antagonists are known to cause. In the present study, we determined what dose of memantine is required to protect the adult rat brain against an NMDA receptor-mediated excitotoxic process and then tested that dose and a range of lower doses to determine whether the drug in this dose range is associated with significant side effects. Consistent with previous research, we found that memantine confers a neuroprotective effect beginning at an intraperitoneal dose of 20 mg/kg, a dose that we found, contrary to previous reports, produces locomotor disturbances severe enough to preclude testing for learning and memory effects. We then determined that, at intraperitoneal doses of 10 and 5 mg/kg, memantine disrupts both memory and locomotor behaviors. Rats treated with these doses performed at control-like levels in learning a hole-board task but were significantly impaired in demonstrating what they had learned when tested 24 h later. This impairment of memory retention was not state dependent in that it was demonstrable regardless of whether the rats were or were not exposed to memantine on the day of retention testing. We conclude that, in the adult rat, memantine behaves like other NMDA antagonists in that it is neuroprotective only at doses that produce intolerable side effects, including memory impairment. PMID:16611808

  4. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  5. Mesenteric lymph flow in adult and aged rats.

    PubMed

    Akl, Tony J; Nagai, Takashi; Coté, Gerard L; Gashev, Anatoliy A

    2011-11-01

    The objective of study was to evaluate the aging-associated changes, contractile characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction amplitude, contraction frequency, and fractional pump flow, lymph flow velocity, wall shear stress, and minute active wall shear stress load were determined in MLV in vivo before and after N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) application at 100 μM. The active pumping of the aged rat MLV in vivo was found to be severely depleted, predominantly through the aging-associated decrease in lymphatic contractile frequency. Such changes correlate with enlargement of aged MLV, which experienced much lower minute active shear stress load than adult vessels. At the same time, pumping in aged MLV in vivo may be rapidly increased back to levels of adult vessels predominantly through the increase in contraction frequency induced by nitric oxide (NO) elimination. Findings support the idea that in aged tissues surrounding the aged MLV, the additional source of some yet unlinked lymphatic contraction-stimulatory metabolites is counterbalanced or blocked by NO release. The comparative analysis of the control data obtained from experiments with both adult and aged MLV in vivo and from isolated vessel-based studies clearly demonstrated that ex vivo isolated lymphatic vessels exhibit identical contractile characteristics to lymphatic vessels in vivo. PMID:21873496

  6. Perinatal undernutrition programmes thyroid function in the adult rat offspring.

    PubMed

    Ayala-Moreno, Rosario; Racotta, Radu; Anguiano, Brenda; Aceves, Carmen; Quevedo, Lucía

    2013-12-01

    Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40% food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3'-triiodothyronine (T3) levels but had normal thyroxine (T4) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T3 (total and free) and total T4 levels, but low free T4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100%) and T4 (non-response v. 17%) levels, a significant decrease in leptin levels (75 v. 32%) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus-pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism. PMID:23800456

  7. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  8. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  9. The subventricular zone is the developmental milestone of a 6-layered neocortex: comparisons in metatherian and eutherian mammals.

    PubMed

    Cheung, Amanda F P; Kondo, Shinichi; Abdel-Mannan, Omar; Chodroff, Rebecca A; Sirey, Tamara M; Bluy, Lisa E; Webber, Natalie; DeProto, Jamin; Karlen, Sarah J; Krubitzer, Leah; Stolp, Helen B; Saunders, Norman R; Molnár, Zoltán

    2010-05-01

    The major lineages of mammals (Eutheria, Metatheria, and Monotremata) diverged more than 100 million years ago and have undergone independent changes in the neocortex. We found that adult South American gray short-tailed opossum (Monodelphis domestica) and tammar wallaby (Macropus eugenii) possess a significantly lower number of cerebral cortical neurons compared with the mouse (Mus musculus). To determine whether the difference is reflected in the development of the cortical germinal zones, the location of progenitor cell divisions was examined in opossum, tammar wallaby, and rat. The basic pattern of the cell divisions was conserved, but the emergence of a distinctive band of dividing cells in the subventricular zone (SVZ) occurred relatively later in the opossum (postnatal day [P14]) and the tammar wallaby (P40) than in rodents. The planes of cell divisions in the ventricular zone (VZ) were similar in all species, with comparable mRNA expression patterns of Brn2, Cux2, NeuroD6, Tbr2, and Pax6 in opossum (P12 and P20) and mouse (embryonic day 15 and P0). In conclusion, the marsupial neurodevelopmental program utilizes an organized SVZ, as indicated by the presence of intermediate (or basal) progenitor cell divisions and gene expression patterns, suggesting that the SVZ emerged prior to the Eutherian-Metatherian split. PMID:19726493

  10. NMDA receptors are the basis for persistent network activity in neocortex slices

    PubMed Central

    Favero, Morgana

    2015-01-01

    During behavioral quiescence the neocortex generates spontaneous slow oscillations that consist of Up and Down states. Up states are short epochs of persistent activity, but their underlying source is unclear. In neocortex slices of adult mice, we monitored several cellular and network variables during the transition between a traditional buffer, which does not cause Up states, and a lower-divalent cation buffer, which leads to the generation of Up states. We found that the resting membrane potential and input resistance of cortical cells did not change with the development of Up states. The synaptic efficacy of excitatory postsynaptic potentials mediated by non-NMDA receptors was slightly reduced, but this is unlikely to facilitate the generation of Up states. On the other hand, we identified two variables that are associated with the generation of Up states: an enhancement of the intrinsic firing excitability of cortical cells and an enhancement of NMDA-mediated responses evoked by electrical or optogenetic stimulation. The fact that blocking NMDA receptors abolishes Up states indicates that the enhancement in intrinsic firing excitability alone is insufficient to generate Up states. NMDA receptors have a crucial role in the generation of Up states in neocortex slices. PMID:25878152

  11. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  12. TIN DISTRIBUTION IN ADULT RAT TISSUES AFTER EXPOSURE TO TRIMETHYLTIN AND TRIETHYLTIN

    EPA Science Inventory

    The time course of distribution of tin in the adult rat was determined in brain, liver kidney, heart, and blood following single ip administrations of trimethyltin hydroxide (TMT) and triethyltin bromide (TET). Adult Long-Evans rats were killed 1 hr, 4 hr, 12 hr, 24 hr, 5 days, 1...

  13. DERMAL PENETRATION OF [14C] CAPTAN IN YOUNG AND ADULT RATS

    EPA Science Inventory

    Dermal penetration of [14C] Captan was determined in young (33 day old) and adult (82 day old) female Fischer 344 rats by an in vivo method and two in vitro methods. ermal penetration in vivo at 72 hours was about 9% of the dose in both young and adult rats. o significant differe...

  14. Stability and Autolysis of Cortical Neurons in Post-Mortem Adult Rat Brains

    PubMed Central

    Sheleg, Sergey V; LoBello, Janine R; Hixon, Hugh; Coons, Stephen W; Lowry, David; Nedzved, Mikhail K

    2008-01-01

    We investigated the dynamics of autolytic damage of the cortical neurons in adult brains for 24 hours at room temperature (+20°C) after cardiac arrest. The progressive histological and ultrastructural changes were documented using routine and immunohistochemical staining as well as electron microscopy. Our results demonstrated that there were no autolytic damages in the ultrastructure of cerebral neurons in the first 6 hours after warm cardiac arrest, in agreement with previous studies in other mammals. Interestingly, the activation of caspase-3 was observed in a significant number of neurons of the cerebellum and neocortex 9 hours following cardiac arrest. No significant changes related to autolysis were observed using amnio-cupric acid and Nissl (thionine) staining. PMID:18784829

  15. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  16. Decline of taste sensitivity in protein deficient adult rats.

    PubMed

    Ohara, I; Tabuchi, R; Kimura, M; Itokawa, Y

    1995-05-01

    The influence of dietary protein levels on taste sensitivity was studied in adult rats. Low protein diets of 0.0, 2.5, or 5.0% purified egg protein (PEP) were fed to animals for 28 days. Two bottle choice preference tests between aqueous solutions of either 2, 9, 17, or 86 mM sodium chloride and deionized water were conducted in an ascending order on days 14, 16, 18, and 20. Urine samples were collected for zinc and creatinine analysis. Blood samples were also collected for measuring serum zinc and creatinine concentrations. Scanning electron microscopy was performed to observe rats' tongue epithelia. Protein free diet group showed significantly lower taste sensitivity and renal reabsorption rate than other protein containing diet groups, while serum zinc and creatinine concentrations, and creatinine clearance were not affected by dietary protein level. Degeneration of filiform papillae and imperforation of taste pore of fungiform papillae were observed in protein free diet group. This experiment implies at least 2.5% dietary protein is required to manifest normal taste function in the adult. PMID:7610145

  17. Chronic In Vivo Imaging of Ponto-Cerebellar Mossy Fibers Reveals Morphological Stability during Whisker Sensory Manipulation in the Adult Rat123

    PubMed Central

    Rylkova, Daria; Crank, Aidan R.

    2015-01-01

    Abstract The cerebellum receives extensive disynaptic input from the neocortex via the basal pontine nuclei, the neurons of which send mossy fiber (MF) axons to the granule cell layer of the contralateral cerebellar hemisphere. Although this cortico-cerebellar circuit has been implicated in tasks such as sensory discrimination and motor learning, little is known about the potential role of MF morphological plasticity in the function of the cerebellar granule cell layer. To address this issue, we labeled MFs with EGFP via viral infection of the basal pons in adult rats and performed in vivo two-photon imaging of MFs in Crus I/II of the cerebellar hemisphere over a period of several weeks. Following the acquisition of baseline images, animals were housed in control, enriched, or deprived sensory environments. Morphological dynamics were assessed by tracing MF axons and their terminals, and by tracking the stability of filopodia arising from MF terminal rosettes. MF axons and terminals were found to be remarkably stable. Parameters derived neither from measurements of axonal arbor geometry nor from the morphology of individual rosettes and their filopodial extensions significantly changed under control conditions over 4 weeks of imaging. Increasing whisker stimulation by manipulating the sensory environment or decreasing such stimulation by whisker trimming also failed to alter MF structure. Our studies indicate that pontine MF axons projecting to Crus I/II in adult rats do not undergo significant structural rearrangements over the course of weeks, and that this stability is not altered by the sustained manipulation of whisker sensorimotor experience. PMID:26693178

  18. Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

    PubMed

    Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

    2016-08-01

    The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016. PMID:25533183

  19. Beta-cyfluthrin induced neurobehavioral impairments in adult rats.

    PubMed

    Syed, Farah; Chandravanshi, Lalit P; Khanna, Vinay K; Soni, Inderpal

    2016-01-01

    Beta-cyfluthrin (CYF) is a commonly used synthetic pyrethroid having both agricultural and domestic applications. The present study aimed to evaluate the neurobehavioural effects of beta-cyfluthrin in adult rats administered at doses 25 mg/kg body weight/day and 12.5 mg/kg body weight/day for a period of 30 days. Motor coordination and spatial memory were found to be impaired by beta-cyfluthrin. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), epinephrine (EPN), and serotonin (5-HT) decreased in frontal cortex, corpus striatum and hippocampus of treated rats. At the same time, significantly elevated levels of homovanillic acid (HVA) and nor-epinephrine (NE) were measured. Beta-cyfluthrin inhibited the activity of acetylcholinesterase (AChE) in all the regions of the brain. Hippocampal choline acetyltransferase (ChAT) expression was reduced 3.1 and 4.7 fold by the two doses respectively. Impairment of the antioxidant defense system, evident by decrease in the levels of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) was seen in the treated rats. The neurochemical alterations manifested were more pronounced in the high dose group as the effects persisted even after withdrawal of exposure. PMID:26604153

  20. Effect of exposure to diazinon on adult rat's brain.

    PubMed

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain. PMID:24217015

  1. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N.; Post, Jeremy; Woods, Amina S.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.

    2009-01-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. PMID:19218497

  2. Activity of putative cognition enhancers in kynurenate test performed with human neocortex slices.

    PubMed

    Pittaluga, A; Pattarini, R; Andrioli, G C; Viola, C; Munari, C; Raiteri, M

    1999-07-01

    Some cognition enhancers were previously shown to potently prevent antagonism of the N-methyl-D-aspartate (NMDA)-evoked release of norepinephrine (NE) brought about in slices of rat hippocampus by kynurenic acid, an endogenous NMDA receptor blocker. We have examined the impact of putative nootropic agents in the kynurenate test performed with slices of human cerebral cortex from patients undergoing neurosurgery. In slices of human neocortex, local application of NMDA evoked release of [3H]NE; the effect of NMDA was antagonized by several NMDA receptor antagonists, including kynurenic acid. The antagonism of the NMDA-evoked [3H]NE release produced by 300 microM kynurenate was potently (EC50 <10 microM) prevented by most of the nootropics tested, including aniracetam, oxiracetam, D-cycloserine, and the glutamate analog CR 2249 (but not its enantiomer CR 2361). Nicotine or tacrine (up to 10 microM) did not show any effect in the kynurenate test. Nicotine (30-100 microM) itself increased the release of [3H]NE; interestingly, the nicotine-evoked overflow was blocked not only by the nicotin receptor antagonist mecamylamine but also by NMDA receptor antagonists, suggesting an indirect mechanism mediated by glutamate/aspartate release. To conclude, the similarities between the data obtained here with human neocortex slices and those previously obtained in the rat indicate that the kynurenate test performed with rat brain slices may represent a useful biochemical assay to study cognition-enhancing drugs. PMID:10381808

  3. Diminished Presynaptic GABAB Receptor Function in the Neocortex of a Genetic Model of Absence Epilepsy

    PubMed Central

    Inaba, Yugi; D’Antuono, Margherita; Bertazzoni, Giuliano; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    Changes in GABAB receptor subunit expression have been recently reported in the neocortex of epileptic WAG/Rij rats that are genetically prone to experience absence seizures. These alterations may lead to hyperexcitability by down-regulating the function of presynaptic GABAB receptors in neocortical networks as suggested by a reduction in paired-pulse depression. Here, we tested further this hypothesis by analyzing the effects induced by the GABAB receptor agonist baclofen (0.1–10 μM) on the inhibitory events recorded in vitro from neocortical slices obtained from epileptic (>180 day-old) WAG/Rij and age-matched, non-epileptic control (NEC) rats. We found that higher doses of baclofen were required to depress pharmacologically isolated, stimulus-induced IPSPs generated by WAG/Rij neurons as compared to NEC. We also obtained similar evidence by comparing the effects of baclofen on the rate of occurrence of synchronous GABAergic events recorded by WAG/Rij and NEC neocortical slices treated with 4-aminopyridine + glutamatergic receptor antagonists. In conclusion, these data highlight a decreased function of presynaptic GABAB receptors in the WAG/Rij rat neocortex. We propose that this alteration may contribute to neocortical hyperexcitability and thus to absence seizures. PMID:19176980

  4. Levels of homology and the problem of neocortex.

    PubMed

    Dugas-Ford, Jennifer; Ragsdale, Clifton W

    2015-07-01

    The neocortex is found only in mammals, and the fossil record is silent on how this soft tissue evolved. Understanding neocortex evolution thus devolves to a search for candidate homologous neocortex traits in the extant nonmammalian amniotes. The difficulty is that homology is based on similarity, and the six-layered neocortex structure could hardly be more dissimilar in appearance from the nuclear organization that is so conspicuous in the dorsal telencephalon of birds and other reptiles. Recent molecular data have, however, provided new support for one prominent hypothesis, based on neuronal circuits, that proposes the principal neocortical input and output cell types are a conserved feature of amniote dorsal telencephalon. Many puzzles remain, the greatest being understanding the selective pressures and molecular mechanisms that underlie such tremendous morphological variation in telencephalon structure. PMID:26154980

  5. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  6. Polygonal networks, "geodomes", of adult rat hepatocytes in primary culture.

    PubMed

    Mochizuki, Y; Furukawa, K; Mitaka, T; Yokoi, T; Kodama, T

    1988-01-01

    Polygonal networks, "geodomes", in cultured hepatocytes of adult rats were examined by both light and electron microscopy. On light microscopical examinations of specimens stained with Coomassie blue after the treatment with Triton X-100, the networks were detected 5 days after culture, which consisted of triangles arranged mainly in hexagonal patterns. They surrounded main cell body, looking like a headband, or were occasionally situated over nuclei, looking like a geodesic dome. Scanning electron microscopical observations after Triton treatment revealed that these structures were located underneath surface membrane. Transmission electron microscopical investigations revealed that the connecting fibers of networks consisted of microfilaments which radiated in a compact bundle from electron-dense vertices. PMID:3396075

  7. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

  8. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  9. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain.

    PubMed

    Creeley, Catherine E; Wozniak, David F; Nardi, Anthony; Farber, Nuri B; Olney, John W

    2008-02-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer's disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine's neurotoxic potential has not been investigated. In the present study, we determined that a dose of memantine (20mg/kg, i.p.), considered to be in the therapeutic (neuroprotective) range for rats, causes a mild neurotoxic reaction in the adult rat brain. Co-administration of memantine (20 or 30 mg/kg) with donepezil (2.5-10mg/kg) markedly potentiated this neurotoxic reaction, causing neuronal injury at lower doses of memantine, and causing the toxic reaction to become disseminated and lethal to neurons throughout many brain regions. These findings raise questions about using this drug combination in AD, especially in the absence of evidence that the combination is beneficial, or that either drug arrests or reverses the disease process. PMID:17112636

  10. GONADAL STEROIDS REGULATED THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN THE ADULT MALE RAT HIPPOCAMPUS

    EPA Science Inventory

    This study demonstrates that gonadal steroids (estradiol, testosterone, dihydrotestosterone) can inhibit the expression of glial fibrillary acidic protein and it MRNA in the adult male rat brain. esticular hormones may influence the activity of astrocytes in the intact and lesion...

  11. Cell-type homologies and the origins of the neocortex

    PubMed Central

    Dugas-Ford, Jennifer; Rowell, Joanna J.; Ragsdale, Clifton W.

    2012-01-01

    The six-layered neocortex is a uniquely mammalian structure with evolutionary origins that remain in dispute. One long-standing hypothesis, based on similarities in neuronal connectivity, proposes that homologs of the layer 4 input and layer 5 output neurons of neocortex are present in the avian forebrain, where they contribute to specific nuclei rather than to layers. We devised a molecular test of this hypothesis based on layer-specific gene expression that is shared across rodent and carnivore neocortex. Our findings establish that the layer 4 input and the layer 5 output cell types are conserved across the amniotes, but are organized into very different architectures, forming nuclei in birds, cortical areas in reptiles, and cortical layers in mammals. PMID:23027930

  12. IMMUNOTOXICITY OF TRIBUTYLTIN OXIDE IN RATS EXPOSED AS ADULTS OR PRE-WEANLINGS

    EPA Science Inventory

    A comparison was made between adult and pre-weanling rats of the immunotoxic effects of acute dosing with bis(tri-n-butyltin) oxide (TBT0). dult (9 week old) male Fischer rats were dosed by oral gavage with TBT0 for 10 consecutive days at 2.5 to 10 mg/kg/dose or three times per w...

  13. ALKYTIN INHIBITION OF ATPASE ACTIVITIES IN TISSUE HOMOGENATES AND SUBCELLULAR FRACTIONS FROM NEONATAL AND ADULT RATS

    EPA Science Inventory

    The effects of triethyltin (TET) on ATPase activities in brain and liver homogenates and subcellular fractions were compared in neonatal and adult rats. n 5 day old rats, relative sensitivities to TET inhibition were: brain and liver mitochondrial ATPase >> rain Na+/K+ ATPase > b...

  14. IMMATURE RAT LEYDIG CELLS ARE INTRINSICALLY LESS SENSITIVE THAN ADULT LEYDIG CELLS TO ETHANE DIMETHANESULFONATE

    EPA Science Inventory

    Leydig cells from immature rat tests appear to be insensitive to doses of ethane-1,2-dimethanesulfonate (EDS) which eliminate Leydig cells from adult rat testes. e sought to determine whether this differential response to EDS is intrinsic to the Leydig cell or mediated by other i...

  15. Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

    PubMed

    Bakker, J M; Kavelaars, A; Kamphuis, P J; Cobelens, P M; van Vugt, H H; van Bel, F; Heijnen, C J

    2000-11-15

    Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man. PMID:11067955

  16. Antibody-mediated targeted gene transfer to NMDA NR1-containing neurons in rat neocortex by helper virus-free HSV-1 vector particles containing a chimeric HSV-1 glycoprotein C--Staphylococcus A protein

    PubMed Central

    Cao, Haiyan; Zhang, Guo-rong; Geller, Alfred I.

    2010-01-01

    Because of the heterogeneous cellular composition of the brain, and especially the forebrain, cell type-specific expression will benefit many potential applications of direct gene transfer. The two prevalent approaches for achieving cell type-specific expression are using a cell type-specific promoter or targeting gene transfer to a specific cell type. Targeted gene transfer with Herpes Simplex Virus (HSV-1) vectors modifies glycoprotein C (gC) to replace the heparin binding domain, which binds to many cell types, with a binding activity for a specific cell surface protein. We previously reported targeted gene transfer to nigrostriatal neurons using chimeric gC--glial cell line-derived neurotrophic factor or gC--brain-derived neurotrophic factor protein. Unfortunately, this approach is limited to cells that express the cognate receptor for either neurotrophic factor. Thus, a general strategy for targeting gene transfer to many different types of neurons is desirable. Antibody-mediated targeted gene transfer has been developed for targeting specific virus vectors to specific peripheral cell types; a specific vector particle protein is modified to contain the Staphylococcus A protein ZZ domain, which binds immunoglobulin (Ig) G. Here, we report antibody-mediated targeted gene transfer of HSV-1 vectors to a specific type of forebrain neuron. We constructed a chimeric gC--ZZ protein, and showed this protein is incorporated into vector particles and binds Ig G. Complexes of these vector particles and an antibody to the NMDA receptor NR1 subunit supported targeted gene transfer to NR1-containing neocortical neurons in the rat brain, with long-term (2 months) expression. PMID:20599821

  17. Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia.

    PubMed Central

    Ling, L; Olson, E B; Vidruk, E H; Mitchell, G S

    1996-01-01

    1. This study was designed to test the hypothesis that perinatal suppression of peripheral arterial chemoreceptor inputs attenuates the hypoxic ventilatory response in adult rats. Perinatal suppression of peripheral chemoreceptor activity was achieved by exposing rats to hyperoxia throughout the first month of life. 2. Late-gestation pregnant rats were housed in a 60% O2 environment, exposing the pups to hyperoxia from several days prior to birth until they were returned to normoxia on postnatal day 28. These perinatally treated rats were then reared to adulthood (3-5 months old) in normoxia. In addition to the mother rats, adult male rats were also exposed to hyperoxia, creating an adult-treated control group. Two to four months after the hyperoxic exposure, treated rats were compared with untreated male rats of similar age. 3. A whole-body, flow-through plethysmograph was used to measure hypoxic and hypercapnic ventilatory responses of the unanaesthetized adult rats. In moderate hypoxia (arterial oxygen partial pressure, Pa,O2 approximately 48 mmHg). VE (minute ventilation) and the ratio VE/VCO2 (ventilation relative to CO2 production) increased by 16.7 +/- 4.0 and 35.4 +/- 3.4%, respectively, in perinatal-treated rats (means +/- S.E.M.), but increased more in untreated control rats (51.4 +/- 2.8 and 83.1 +/- 4.3%; both P < 10(-6)). 4. In contrast to the impaired hypoxic ventilatory response, ventilatory responses to hypercapnia (5% CO2) were similar between untreated control and perinatal-treated rats. 5. Impaired hypoxic responsiveness was unique to the perinatal-treated rats since hypoxic ventilatory responses were not attenuated in adult-treated rats. 6. The results indicate that ventilatory responses to hypoxaemia are greatly attenuated in adult rats that had experienced hyperoxia during their first month of life, and suggest that normal hypoxic ventilatory control mechanisms are susceptible to developmental plasticity. Images Figure 2 Figure 3 PMID:8887766

  18. Electroconvulsive seizure induces thrombospondin-1 in the adult rat hippocampus.

    PubMed

    Okada-Tsuchioka, Mami; Segawa, Masahiro; Kajitani, Naoto; Hisaoka-Nakashima, Kazue; Shibasaki, Chiyo; Morinobu, Shigeru; Takebayashi, Minoru

    2014-01-01

    Synaptic dysfunction has recently gained attention for its involvement in mood disorders. Electroconvulsive therapy (ECT) possibly plays a role in synaptic repair. However, the underlying mechanisms remain uncertain. Thrombospondin-1 (TSP-1), a member of the TSP family, is reported to be secreted by astrocytes and to regulate synaptogenesis. We investigated the effects of electroconvulsive seizure (ECS) on the expression of TSPs in the adult rat hippocampus. Single and repeated ECS significantly increased TSP-1 mRNA expression after 2h and returned to sham levels at 24h. Conversely, the TSP-2 and -4 mRNA levels did not change. Only repeated ECS induced TSP-1 proteins. ECS also induced glial fibrillary acidic protein (GFAP) expression. The GFAP expression occurred later than the TSP-1 mRNA expression following single ECS; however, it occurred earlier and was more persistent following repeated ECS. ECS had no effect on the α2δ-1 or neuroligin-1 expressions, both of which are TSP-1 receptors. Furthermore, chronic treatment with antidepressants did not induce the expression of TSP-1 or GFAP. These findings suggest that repeated ECS, but not chronic treatment with antidepressants, induces TSP-1 expression partially via the activation of astrocytes. Therefore, TSP-1 is possibly involved in the synaptogenic effects of ECS. PMID:24121060

  19. Adversity before conception will affect adult progeny in rats.

    PubMed

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress (PCS0) or 2 weeks after the stress ended (PCS2). Their offspring were raised undisturbed until tested in adulthood. PCS offspring showed reduced social interaction; in the acoustic startle test, PCS males were less fearful, whereas PCS females were more fearful; in the shuttle task, PCS0 males avoided shock better; and in the elevated maze, PCS0 females were more active and anxious. The 2-week interval between stress and mating assuaged the effects on offspring activity and shock avoidance but not the changes in social behavior and fear in male and female offspring. Hence, PCS to the dam, even well before pregnancy, influences affective and social behavior in her adult offspring, depending on how long before conception it occurred, the behavior tested, and sex. (PsycINFO Database Record (c) 2009 APA, all rights reserved). PMID:19209986

  20. Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

    PubMed Central

    Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

    2008-01-01

    Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12−17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation. PMID:17445242

  1. Different sensitivity of PPARalpha gene expression to nutritional changes in liver of suckling and adult rats.

    PubMed

    Panadero, Maribel; Herrera, Emilio; Bocos, Carlos

    2005-01-14

    The amount of peroxisome proliferator-activated receptor-alpha (PPARalpha) protein was markedly augmented in the liver of suckling rats compared to adult rats. This different PPARalpha abundance was used to study the sensitivity to nutritional changes in the expression and activity of this receptor. Thus, 10-day-old and adult rats were orally given either glucose, Intralipid or a combination of both diets, and liver mRNA levels of PPARalpha and the PPAR related genes, acyl-CoA oxidase (ACO) and phosphoenolpyruvate carboxykinase (PEPCK), and plasma metabolites were measured. In neonates, the expression of PPARalpha and ACO was seen to increase when the level of FFA in plasma was also high, unless an elevated level of insulin was also present. However, this fatty acid-induced effect was not detected in adult rats. On the contrary, the hepatic expression of PEPCK was modulated by the nutritional changes similarly in both neonates and adult rats. Thus, it may be concluded that the expression of the PPARalpha gene in adult rats seems to be less sensitive to nutritional changes than in neonates. PMID:15607334

  2. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

    PubMed Central

    Wang, Hua; Lau, Benson Wui-Man; Wang, Ning-li; Wang, Si-ying; Lu, Qing-jun; Chang, Raymond Chuen-Chung; So, Kwok-fai

    2015-01-01

    Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID:26889185

  3. Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

    PubMed Central

    Fried, Nathan T.; Moffat, Cynthia; Seifert, Erin L.

    2014-01-01

    Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders. PMID:25252946

  4. The cortical hem regulates the size and patterning of neocortex

    PubMed Central

    Caronia-Brown, Giuliana; Yoshida, Michio; Gulden, Forrest; Assimacopoulos, Stavroula; Grove, Elizabeth A.

    2014-01-01

    The cortical hem, a source of Wingless-related (WNT) and bone morphogenetic protein (BMP) signaling in the dorsomedial telencephalon, is the embryonic organizer for the hippocampus. Whether the hem is a major regulator of cortical patterning outside the hippocampus has not been investigated. We examined regional organization across the entire cerebral cortex in mice genetically engineered to lack the hem. Indicating that the hem regulates dorsoventral patterning in the cortical hemisphere, the neocortex, particularly dorsomedial neocortex, was reduced in size in late-stage hem-ablated embryos, whereas cortex ventrolateral to the neocortex expanded dorsally. Unexpectedly, hem ablation also perturbed regional patterning along the rostrocaudal axis of neocortex. Rostral neocortical domains identified by characteristic gene expression were expanded, and caudal domains diminished. A similar shift occurs when fibroblast growth factor (FGF) 8 is increased at the rostral telencephalic organizer, yet the FGF8 source was unchanged in hem-ablated brains. Rather we found that hem WNT or BMP signals, or both, have opposite effects to those of FGF8 in regulating transcription factors that control the size and position of neocortical areas. When the hem is ablated a necessary balance is perturbed, and cerebral cortex is rostralized. Our findings reveal a much broader role for the hem in cortical development than previously recognized, and emphasize that two major signaling centers interact antagonistically to pattern cerebral cortex. PMID:24948604

  5. Effects of psychostimulants on social interaction in adult male rats.

    PubMed

    Šlamberová, Romana; Mikulecká, Anna; Macúchová, Eva; Hrebíčková, Ivana; Ševčíková, Mária; Nohejlová, Kateryna; Pometlová, Marie

    2015-12-01

    Psychostimulants are known to have a huge impact on different forms of social behaviour. The aim of the present study was to compare the effects of three different psychostimulants [amphetamine, cocaine and 3,4 methylenedimethoxyamphetamine (MDMA)] on social interaction (SI) in adult male rats. The SI test was performed in a familiar arena and under low-stress environmental conditions. Experimental animals received amphetamine (0.5, 1.0, 1.5 mg/kg), cocaine (0.5, 1.0, 1.5, 2.5, 5.0, 10.0 mg/kg) or MDMA (2.5, 5.0, 10 mg/kg) and control animals received saline (1 ml/kg) 45 min before the SI test. Time spent in SI (individual patterns of social behaviour) and nonsocial activities (locomotion and rearing) were video recorded and then analysed offline, with the following results: (a) all doses of amphetamine decreased SI. Specifically, all doses of amphetamine decreased mutual sniffing, and the higher doses also decreased allo-grooming and following behaviours. (b) The higher doses of cocaine decreased SI, especially mutual sniffing, allo-grooming and climbing over. Cocaine at the dose of 5.0 mg/kg increased genital investigation compared with lower doses. (c) All doses of MDMA decreased mutual sniffing and climbing over; the two higher doses decreased allo-grooming behaviour, and only the highest dose decreased following. The two higher doses of amphetamine and all the doses of MDMA increased locomotion and rearing; cocaine did not affect locomotion, but increased rearing at higher doses. In conclusion, the results confirm the well-known finding that psychostimulants suppress SI, but also show novel differences in the effects of psychostimulants on specific patterns of SI. PMID:26061354

  6. Safety of Intracerebroventricular Copper Histidine in Adult Rats

    PubMed Central

    Lem, Kristen E.; Brinster, Lauren R.; Tjurmina, Olga; Lizak, Martin; Lal, Simina; Centeno, Jose A.; Liu, Po-Ching; Godwin, Sarah C.; Kaler, Stephen G.

    2007-01-01

    Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in a P-type ATPase (ATP7A) that normally delivers copper to the developing central nervous system. Infants with large deletions, or other mutations in ATP7A that incapacitate copper transport to the brain, show poor clinical outcomes and subnormal brain copper despite early subcutaneous copper histidine (CuHis) injections. These findings suggest a need for direct central nervous system approaches in such patients. To begin to evaluate an aggressive but potentially useful new strategy for metabolic improvement of this disorder, we studied the acute and chronic effects of CuHis administered by intracerebroventricular (ICV) injection in healthy adult rats. Magnetic resonance imaging (MRI) after ICV CuHis showed diffuse T1-signal enhancement, indicating wide brain distribution of copper after ICV administration, and implying the utility of this paramagnetic metal as a MRI contrast agent. The maximum tolerated dose (MTD) of CuHis, defined as the highest dose that did not induce overt toxicity, growth retardation, or reduce lifespan, was 0.5 mcg. Animals receiving multiple infusions of this MTD showed increased brain copper concentrations, but no significant differences in activity, behavior, and somatic growth, or brain histology compared to saline-injected controls. Based on estimates of the brain copper deficit in Menkes disease patients, CuHis doses 10-fold lower than the MTD found in this study may restore proper brain copper concentration. Our results suggest that ICV CuHis administration have potential as a novel treatment approach in Menkes disease infants with severe mutations. Future trials of direct CNS copper administration in mouse models of Menkes disease will be informative. PMID:17336116

  7. Electrophysiological study of infant and adult rats under acute intoxication with fluoroacetamide.

    PubMed

    Kuznetsov, Sergey V; Jenkins, Richard O; Goncharov, Nikolay V

    2007-01-01

    A study was conducted of acute intoxication of infant and adult Wistar rats with fluoroacetamide (FAA), an inhibitor of oxidative metabolism. FAA was administered orally to adult rats at 1/2 LD(50) and subcutaneously to infant rats at LD(100) or 1/10 LD(50). Electrocardiogram (ECG), respiration and motor activity were registered for 7 days. Clinical analysis of ECG and the heart rate variability (HRV) was carried out to assess the state of the vegetative nervous system. In adult rats, FAA caused marked disturbances in the activity of cardiovascular and respiratory systems, including the development of a potentially lethal acute cor pulmonale. Conversely, there were no significant changes of cardiac function and respiration in infant rats; they died because of extreme emaciation accompanied by retardation of development. In adult rats, bursts of associated cardiac and respiratory tachyarrhythmia, as well as regular high amplitude spasmodic sighs having a deca-second rhythm were observed. In both infant and adult rats, FAA caused short-term enhancement of humoral (metabolic) and sympathetic activities, followed by a gradual and stable predominance of parasympathetic influence on HRV. Under conditions of FAA inhibition of the tricarboxylic acid cycle, the observed physiological reactions may be explained by activation of alternative metabolic pathways. This is also supported by a lack of ontogenetically caused inhibition of spontaneous motor activity in infant rats poisoned with FAA, which highlights the significance of the alternative metabolic pathways for implementation of deca-second and minute rhythms and a lack of a rigid dependence of these rhythms upon activity of neuronal networks. PMID:17351914

  8. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    PubMed Central

    Amrein, Irmgard; Becker, Anton S.; Engler, Stefanie; Huang, Shih-hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K.

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents. PMID

  9. Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2016-07-01

    Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28-53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking. PMID:25950618

  10. Adaptations of young adult rat cortical bone to 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

    1992-01-01

    To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

  11. Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus.

    PubMed

    Bosquiazzo, Verónica L; Vigezzi, Lucía; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2013-11-01

    The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol. PMID:23454116

  12. Effect of different doses of Malaysian honey on reproductive parameters in adult male rats.

    PubMed

    Mohamed, M; Sulaiman, S A; Jaafar, H; Sirajudeen, K N S

    2012-05-01

    The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats. PMID:21592175

  13. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats

    PubMed Central

    AHN, JI HYEON; CHEN, BAI HUI; SHIN, BICH-NA; LEE, TAE-KYEONG; CHO, JEONG HWI; KIM, IN HYE; PARK, JOON HA; LEE, JAE-CHUL; TAE, HYUN-JIN; LEE, CHOONG-HYUN; WON, MOO-HO; LEE, YUN LYUL; CHOI, SOO YOUNG; HONG, SEONGKWEON

    2016-01-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN-immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  14. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats.

    PubMed

    Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Lee, Tae-Kyeong; Cho, Jeong Hwi; Kim, In Hye; Park, Joon Ha; Lee, Jae-Chul; Tae, Hyun-Jin; Lee, Choong-Hyun; Won, Moo-Ho; Lee, Yun Lyul; Choi, Soo Young; Hong, Seongkweon

    2016-07-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN‑immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  15. Testis structure and function in a nongenetic hyperadipose rat model at prepubertal and adult ages.

    PubMed

    França, L R; Suescun, M O; Miranda, J R; Giovambattista, A; Perello, M; Spinedi, E; Calandra, R S

    2006-03-01

    There are few data for hormonal levels and testis structure and function during postnatal development in rats neonatally treated with monosodium L-glutamate (MSG). In our study, newborn male pups were ip injected with MSG (4 mg/g body weight) every 2 d up to 10 d of age and investigated at prepubertal and adult ages. Plasma levels of leptin, LH, FSH, prolactin, testosterone (T), corticosterone, and free T4 (FT4) were measured. MSG rats displayed elevated circulating levels of corticosterone and hyperadiposity/hyperleptinemia, regardless of the age examined; conversely, circulating prolactin levels were not affected. Moreover, prepubertal MSG rats revealed a significant (P < 0.05) reduction in testis weight and the number of Sertoli (SC) and Leydig cells per testis. Leptin plasma levels were severalfold higher (2.41 vs. 8.07; P < 0.05) in prepubertal MSG rats, and these animals displayed plasma LH, FSH, T, and FT4 levels significantly decreased (P < 0.05). Taken together, these data indicate that testis development, as well as SC and Leydig cell proliferation, were disturbed in prepubertal MSG rats. Adult MSG rats also displayed significantly higher leptin plasma levels (7.26 vs. 27.04; P < 0.05) and lower (P < 0.05) LH and FSH plasma levels. However, T and FT4 plasma levels were normal, and no apparent alterations were observed in testis structure of MSG rats. Only the number of SCs per testis was significantly (P < 0.05) reduced in the adult MSG rats. In conclusion, although early installed hyperadipose/hyperleptinemia phenotype was probably responsible for the reproductive axis damages in MSG animals, it remains to be investigated whether this condition is the main factor for hypothalamus-pituitary-gonadal axis dysfunction in MSG rats. PMID:16339210

  16. Modeling binge-like ethanol drinking by peri-adolescent and adult P rats

    PubMed Central

    Bell, Richard L.; Rodd, Zachary A.; Smith, Rebecca J.; Toalston, Jamie E.; Franklin, Kelle M.; McBride, William J.

    2011-01-01

    Alcohol binge-drinking, especially among adolescents and young adults, is a serious public health concern. The present study examined ethanol binge-like drinking by peri-adolescent [postnatal days (PNDs 30—72)] and adult (PNDs 90—132) alcohol-preferring (P) rats with a drinking-in-the-dark—multiple-scheduled-acces (DID-MSA) procedure used by our laboratory. Male and female P rats were provided concurrent access to 15% and 30% ethanol for three 1-hr sessions across the dark cycle 5 days/week. For the 1st week, adolescent and adult female P rats consumed 3.4 and 1.6 g/kg of ethanol, respectively, during the 1st hr of access, whereas for male rats the values were 3.5 and 1.1 g/kg of ethanol, respectively. Adult intakes increased to ~2.0 g/kg/hr and adolescent intakes decreased to ~2.5 g/kg/hr across the 6 weeks of ethanol access. The daily ethanol intake of adult DID-MSA rats approximated or modestly exceeded that seen in continuous access (CA) rats or the selection criterion for P rats (≥ 5g/kg/day). However, in general, the daily ethanol intake of DID-MSA peri-adolescent rats significantly exceeded that of their CA counterparts. BELs were assessed at 15-min intervals across the 3rd hr of access during the 4th week. Ethanol intake was 1.7 g/kg vs. 2.7 g/kg and BELs were 57 mg% vs. 100 mg% at 15- and 60-min, respectively. Intoxication induced by DID-MSA in female P rats was assessed during the 1st vs. 4th week of ethanol access. Level of impairment did not differ between the 2 weeks (106 vs. 97 sec latency to fall, 120 sec criterion) and was significant (vs. naïve controls) only during the 4th week. Overall, these findings support the use of the DID-MSA procedure in rats, and underscore the presence of age- and sex-dependent effects mediating ethanol binge-like drinking in P rats. PMID:21824488

  17. Cellular transfer of experimental allergic encephalomyelitis employing suckling and adult Lewis rats.

    PubMed

    Fujinami, R S; Paterson, P Y

    1981-07-01

    Experiments designed to assess the importance of age of donors and recipients in cellular transfer of experimental allergic encephalomyelitis (EAE) in inbred Lewis rats indicate: (a) that lymph node cells (LNC) of suckling rats sensitized to neuroantigen-adjuvant are just as effective in transfer of the disease to adult recipients as LNC from similarly sensitized adult donors, (b) that EAE can be transferred to suckling rats just as well as adults using lymphoid cells from either suckling or adult donors, and (c) while relatively low numbers of sensitized splenocytes from suckling or adult donors may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis rats. PMID:6973635

  18. Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats.

    PubMed

    Carou, Maria E; Ponzo, Osvaldo J; Cardozo Gutierrez, Romina P; Szwarcfarb, Berta; Deguiz, Maria L; Reynoso, Roxana; Carbone, Silvia; Moguilevsky, Jaime A; Scacchi, Pablo

    2008-09-01

    4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats. PMID:21783915

  19. The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

    PubMed Central

    Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

    2016-01-01

    Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

  20. Effect of High Glucose on Stress-Induced Senescence of Nucleus Pulposus Cells of Adult Rats

    PubMed Central

    Kong, Jae-Gwan; Lee, Donghwan; Park, Eun-Young

    2015-01-01

    Study Design In vitro cell culture model. Purpose We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells. Overview of Literature DM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells. Methods Adult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-β-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways. Results The mean SA-β-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations. Conclusions The current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM. PMID:25901224

  1. Relation of the insular claustrum to the neocortex in Insectivora.

    PubMed

    Narkiewicz, O; Mamos, L

    1990-01-01

    The claustra of 9 species of Insectivora (Sorex araneus, Sorex minutus, Tenrec ecaudatus, Solenodon paradoxus, Neomys fodiens, Erinaceus europaeus, Talpa europaea, Desmana moschata, Potamogale velox) were investigated. In all examined animals we found two parts of the insular claustrum: the main part called by us the pars principalis and more medially situated lamina profunda claustri. In the "basal" Insectivora the main part is in close contact with the layer VIa of the neocortex. In some more developed "basal" and in all "progressive" Insectivora the area capsularis appears. Dorsolaterally it separates the main part of the insular claustrum from the neocortex and possesses, besides neurons, also numerous fibers of the extreme capsule. The above data strongly suggest that in the phylogenesis the insular claustrum originates from the cortex from which it gets separated by the extreme capsule. Lamina profunda claustri is rather a narrow band of neurons situated on the medial side of the pars principalis and mostly separated from it by a thin lamina of white substance. Lamina profunda is continuous with the layer VIb of the neocortex. PMID:1707077

  2. Zinc deficiency induces depression-like symptoms in adult rats.

    PubMed

    Tassabehji, Nadine M; Corniola, Rikki S; Alshingiti, Almamoun; Levenson, Cathy W

    2008-10-20

    There is mounting evidence suggesting a link between serum zinc levels and clinical depression. Not only is serum zinc negatively correlated with the severity of symptoms, but zinc levels appear to be lowest in patients who do not respond to antidepressant drug therapy. It is not known if reduced zinc levels are contributing to depression, or the result of dietary or other factors associated with major depression. Thus, we designed this study to test the hypothesis that dietary zinc deficiency would induce depression-like behaviors in rats. Two-month-old male rats were fed zinc adequate (ZA, 30 ppm), deficient (ZD, 1 ppm), or supplemented (ZS, 180 ppm) diets for 3 weeks. Consistent with the development of depression, ZD rats displayed anorexia (p<0.001), anhedonia (reduced saccharin:water intake, p< 0.001), and increased anxiety-like behaviors in a light-dark box test (p<0.05). Furthermore, the antidepressant drug fluoxetine (10 mg/kg body wt) reduced behavioral despair, as measured by the forced swim test, in rats fed the ZA and ZS rats (p<0.05), but was ineffective in ZD rats. Together these studies suggest that zinc deficiency leads to the development of depression-like behaviors that may be refractory to antidepressant treatment. PMID:18655800

  3. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-09-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  4. Conditioned Place Preference and Self-Administration Induced by Nicotine in Adolescent and Adult Rats

    PubMed Central

    Ahsan, Hafiz Muhammad; de la Peña, June Bryan I.; Botanas, Chrislean Jun; Kim, Hee Jin; Yu, Gu Yong; Cheong, Jae Hoon

    2014-01-01

    Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine. PMID:25414778

  5. Conditioned place preference and self-administration induced by nicotine in adolescent and adult rats.

    PubMed

    Ahsan, Hafiz Muhammad; de la Peña, June Bryan I; Botanas, Chrislean Jun; Kim, Hee Jin; Yu, Gu Yong; Cheong, Jae Hoon

    2014-09-01

    Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine. PMID:25414778

  6. Postnatal masculinization alters the HPA axis phenotype in the adult female rat

    PubMed Central

    Seale, JV; Wood, SA; Atkinson, HC; Harbuz, MS; Lightman, SL

    2005-01-01

    The ability of postnatal testosterone propionate (TP) to masculinize both behaviour and gonadal cyclicity in the female rat is well documented. We have investigated whether postnatal androgen also has an organizational effect on another sexually dimorphic neuroendocrine system – the hypothalamo-pituitary-adrenal (HPA) axis. Female rats were exposed to a single injection of testosterone propionate (TP) or oil within 24 h of birth. As adults, rats were either ovariectomized and given 17β-oestradiol replacement (OVXE2) or sham ovariectomized with cholesterol implants (SHOVX). An automated sampling system collected blood from unanaesthetized adult female rats every 10 min over a 24-h period, during a mild psychological stress (noise) and following an immunological lipopolysaccharide stress (LPS). Neonatal TP-treated SHOVX rats had a significant reduction in the number, height, frequency and amplitude of corticosterone pulses over the basal 24-h period, compared to both the neonatal oil-treated and TP-treated OVXE2 animals. The corticosterone response to both noise and LPS was also significantly decreased for the TP-treated SHOVX females. Three hours post-LPS administration, TP females had significantly lower values of paraventricular nucleus (PVN) corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and anterior pituitary proopiomelanocortin (POMC) mRNAs and greater PVN glucocorticoid receptor (GR) mRNA expression compared to the oil-treated controls. E2 replacement in adult TP rats normalized all the mRNA levels, except for PVN GR mRNA which did fall towards the levels of the oil-control animals. A single injection of TP within 24 h of birth disrupts the development of the characteristic female pattern of corticosterone secretion and the normal female HPA response to stress, resulting in a pattern similar to that seen in males. These effects can be reversed by E2 treatment in the adult TP female rat. PMID:15611026

  7. Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats

    PubMed Central

    Carroll, Marilyn E.

    2010-01-01

    Rationale In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress. Objective The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior. Methods On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure. Results Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues. Conclusion These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress. PMID:19953228

  8. Dietary Iron Concentration May Influence Aging Process by Altering Oxidative Stress in Tissues of Adult Rats

    PubMed Central

    Arruda, Lorena Fernandes; Arruda, Sandra Fernandes; Campos, Natália Aboudib; de Valencia, Fernando Fortes; Siqueira, Egle Machado de Almeida

    2013-01-01

    Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively) for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl) and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b) and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2) and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2) relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging. PMID:23593390

  9. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

    During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and

  10. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

    PubMed Central

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-01-01

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

  11. Ethanol induces second-order aversive conditioning in adolescent and adult rats

    PubMed Central

    Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia; Molina, Juan Carlos; Spear, Norman E.

    2011-01-01

    Alcohol abuse and dependence is considered a developmental disorder with etiological onset during late childhood and adolescence, and understanding age-related differences in ethanol sensitivity is important. Low to moderate ethanol doses (0.5 and 2.0 g/kg, i.g.) induce single-trial, appetitive second-order place conditioning (SOC) in adolescent, but not adult, rats. Recent studies have demonstrated that adolescents may be less sensitive than adults to the aversive properties of ethanol, reflected by conditioned taste aversion. The present study assessed the aversive motivational effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescent and adults, respectively) using SOC. These doses were derived from Experiment 1, which found similar blood and brain ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol, respectively. In Experiment 2, animals received ethanol or vehicle paired with intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or three conditioning trials, rats were presented with the CS1 while in a distinctive chamber (CS2). When tested for CS2 preference, ethanol-treated animals exhibited reduced preference for the CS2 compared with controls. This result, indicative of ethanol-mediated aversive place conditioning, was similar for adolescents and adults, for females and males, and after one, two, or three training trials. One finding, however, suggested that adolescents were less sensitive than adults to ethanol’s aversive effects at the intermediate level of training. In conjunction with previous results, the present study showed that in adolescent rats subjected to SOC, ethanol’s hedonic effects vary from appetitive to aversive as the ethanol dose increases. Adolescent and adult animals appear to perceive the post-ingestive effects of high-dose ethanol as similarly aversive when assessed by SOC. PMID:21187242

  12. Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats.

    PubMed

    Warszawski, D; Gorodischer, R; Kaplanski, J

    1978-01-01

    The toxicity of aminophylline and caffeine was studied in adult and 2-day-old rats following a single subcutaneous injection of the respective drug. Following the injection of high doses of either methylxanthine, adult rats developed convulsions, tremors, lethargy and licking of lips. In adult rats, the LD50 of caffeine and aminophylline was the same after 24 h and after 1 week of observation: caffeine 265 mg/kg, and aminophylline 202 mg/kg (theophylline base 172 mg/kg). In young rats, the LD50 was greater when the observation was carried out for 1 week than at 24 h after the injection; at 24 h: caffeine 220 mg/kg, and aminophylline 169 mg/kg (theophylline base 144 mg/kg); at 1 week: caffeine 155 mg/kg, and aminophylline 140 mg/kg (theophylline base 119 mg/kg). Young rats failed to gain weight at a normal rate after administration of either methylxanthine. The greater toxicity of both methylxanthines in newborn animals may be at least partly due to the extremely slow elimination of theophylline and caffeine in the neonate. PMID:698326

  13. Muscle mechanical properties of adult and older rats submitted to exercise after immobilization

    PubMed Central

    Kodama, Fábio Yoshikazu; Camargo, Regina Celi Trindade; Job, Aldo Eloizo; Ozaki, Guilherme Akio Tamura; Koike, Tatiana Emy; Camargo Filho, José Carlos Silva

    2012-01-01

    Objectives To describe the effects of immobilization, free remobilization and remobilization by physical exercise about mechanical properties of skeletal muscle of rats of two age groups. Methods 56 Wistar rats divided into two groups according to age, an adult group (five months) and an older group (15 months). These groups were subdivided in: control, immobilized, free remobilized and remobilized by physical exercise. The pelvic limb of rats was immobilized for seven days. The exercise protocol consisted of five swimming sessions, once per day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile tests, and evaluated the properties: load at the maximum limit, stretching at the maximum limit and stiffness. Results The immobilization reduced the values of load at the maximum limit and the remobilization protocols were not sufficient to restore control levels in adult group and older rats. The stretching at the maximum limit differs only in the older group. Conclusions The immobilization reduces the muscle's ability to bear loads and exercise protocol tends to restore the default at control values in adult and older rats. The age factor only interfered in the stretching at the maximum limit, inducing a reduction of this property in the post-immobilization. Level of Evidence II, Investigating the Results of Treatment. PMID:24453606

  14. MAINTENANCE OF TESTOSTERONE PRODUCTION BY PURIFIED ADULT RAT LEYDIG CELLS FOR THREE DAYS IN VITRO

    EPA Science Inventory

    Using a preparation of highly purified, adult rat Leydig cells and conditions of culture which we found to optimize testosterone production during 24 h, we sought to maintain optimal testosterone production for 3 d. eydig cells cultured on Cytodex 3 beads at 19% O2 in Dulbecco's ...

  15. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS. M.N. Logan1, J.R. Thibodeaux2, R.G. Hanson2, C. Lau2. 1North Carolina Central University, Durham, NC, 2Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

    Perfluor...

  16. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  17. Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

    ERIC Educational Resources Information Center

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

  18. REPRODUCTIVE EFFECTS OF LOW ACUTE DOSES OF CADMIUM CHLORIDE IN ADULT MALE RATS

    EPA Science Inventory

    Adult male Sprague-Dawley rats were injected sc with cadmium (Cd, as cadmium chloride) in doses ranging from 1.6 to 152 micromol Cd/kg body weight (body wt). Fourteen days after dosing, animals were evaluated for reproductive damage. Evaluations for each animal included tests, se...

  19. 5,7-DIHYDROXYTRYPTAMINE INJECTIONS INCREASE GLIAL FIBRILLARY ACIDIC PROTEIN IN THE HYPOTHALAMUS OF ADULT RATS

    EPA Science Inventory

    The distribution and level of glial fibrillary acidic protein (GFAP) were determined in the adult rat hypothalamus following axotomy of serotonin (5-HT) neurons. even days after unilateral intrahypothalamic injection of the 5-HT neurotoxic, 5,7- dihydroxytryptamine, there gas a m...

  20. IN VITRO ALUMINUM INHIBITION OF BRAIN PHOSPHOINOSITIDE METABOLISM:COMPARISON OF NEONATAL AND ADULTS RATS

    EPA Science Inventory

    Recent evidence indicates that the neurotoxic metal aluminum interferes with the phosphoinositide second messenger system in adult rats both in vitro and in vivo. e have examined the age-related effects of aluminum chloride (AlCl3) on receptor-stimulated inositol phosphate (IP) a...

  1. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  2. Culture and proliferation of highly purified adult Schwann cells from rat, dog, and man.

    PubMed

    Haastert-Talini, Kirsten

    2012-01-01

    This chapter presents fast and easy protocols to obtain highly purified cultures of proliferating adult rat, canine, and human Schwann cells. Cell preparation from predegenerated adult sciatic nerves combined with the use of melanocyte growth medium supplemented with forskolin, fibroblast growth factor-2, pituitary extract, and heregulin as selective, serum-free culture medium and two methods for a consecutive cell-enrichment step are described. Our protocols result in approximately 90% pure Schwann cell cultures (or higher). The average time to obtain highly purified in vitro cultures of adult Schwann cells is 21 days. PMID:22367812

  3. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    PubMed

    Oosthuizen, M K; Amrein, I

    2016-06-01

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. PMID:26979050

  4. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    PubMed

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion. PMID:27512001

  5. Autonomic activation associated with ethanol self-administration in adult female P rats

    PubMed Central

    Bell, Richard L.; Rodd, Zachary A.; Toalston, Jamie E.; McKinzie, David L.; Lumeng, Lawrence; Li, Ting-Kai; McBride, William J.; Murphy, James M.

    2008-01-01

    The present study examined changes in heart rate (HR) prior to and during limited access ethanol drinking in adult female P rats. P rats were implanted with radiotelemetric transmitters to measure HR. Daily testing involved a 90-min pre-test period (water only available) and a subsequent 90-min test period [either water (W) or ethanol available]. After a week of habituation, one ethanol group had access to ethanol for 7 weeks (CE), and another ethanol group had access for 4 weeks, was deprived for 2 weeks and then had access for a final week (DEP). Analyses of HR revealed that CE and DEP rats had significantly higher HR than W rats during test periods that ethanol was present and that DEP rats displayed higher HR during the early test period of the ethanol deprivation interval, as well. These data indicate that ethanol drinking induces HR activation in adult female P rats, and that this activation can be conditioned to the test cage environment, paralleling reports on contextual conditioning and cue-reactivity in alcoholics exposed to alcohol-associated stimuli. Therefore, this behavioral test may prove advantageous in screening pharmacotherapies for reducing craving and relapse, which are associated with cue-reactivity in abstinent alcoholics. PMID:18713644

  6. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  7. Juvenile play conditions sexual partner preference in adult female rats.

    PubMed

    Paredes-Ramos, Pedro; Miquel, Marta; Manzo, Jorge; Coria-Avila, Genaro A

    2011-10-24

    Rats can display a conditioned partner preference for individuals that bear an odor previously associated with sexual reward. Herein we tested the possibility that odors associated with the reward induced by social play in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups of 31-day-old, single-housed female rats were formed, and were given daily 30-min periods of social play with scented females. In one group, almond scent was paired with juvenile play during conditioning trials, whereas lemon scent functioned as a novel odor in the final test. The counterbalanced group received the opposite association. At age 42, females were tested for play partner preference with two males, one almond-scented and one lemon-scented. In both groups females displayed a play partner preference only for males scented with the paired odor. They were ovariectomized, hormone-primed, and at age 55 were tested for sexual partner preference with two scented stud males. Females displayed a sexual preference towards males scented with the paired odor as observed with more visits, solicitations, hops and darts, intromissions and ejaculations. These results indicate that olfactory stimuli paired with juvenile play affects later partner choice for play as well as for sex in female rats. PMID:21777597

  8. Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.

    PubMed

    Onifer, S M; Cannon, A B; Whittemore, S R

    1997-01-01

    Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI

  9. Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

    PubMed Central

    Lozano, German; Elmaghrabi, Ayah; Salley, Jordan; Siddique, Khurrum; Gattineni, Jyothsna

    2014-01-01

    The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min−1·100 g body wt−1 in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min−1·100 g body wt−1, which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min−1·100 g body wt−1). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing. PMID:25537745

  10. Neonatal Cystitis-Induced Colonic Hypersensitivity in Adult Rats: A Model of Viscero-Visceral Convergence

    PubMed Central

    Miranda, Adrian; Mickle, Aaron; Schmidt, Jamie; Zhang, Zhihong; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

    2011-01-01

    Background The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms. Methods Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days (postnatal days 14th–16th). The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissue. CRD or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-D-aspartic acid (NMDA) NR1 subunit in the L6-S1 spinal cord was examined using Western blot. Results The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan rats was significantly higher than the control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (p > 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared to saline treated rats (p <0.05). Conclusion Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does results in overexpression of spinal NR1 subunit in adult rats. PMID:21592255

  11. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

    PubMed Central

    Jessberger, Sebastian; Clark, Robert E.; Broadbent, Nicola J.; Clemenson, Gregory D.; Consiglio, Antonella; Lie, D. Chichung; Squire, Larry R.; Gage, Fred H.

    2009-01-01

    New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior. PMID:19181621

  12. Functional Myotube Formation from Adult Rat Satellite Cells in a Defined Serum-free System

    PubMed Central

    McAleer, Christopher W.; Rumsey, John W.; Stancescu, Maria; Hickman, James J.

    2016-01-01

    This manuscript describes the development of a culture system whereby mature contracting myotubes were formed from adult rat derived satellite cells. Satellite cells, extracted from the Tibialis Anterior (TA) of adult rats, were grown in defined serum-free growth and differentiation media, on a non-biological substrate, N-1[3-trimethoxysilyl propyl] diethylenetriamine. Myotubes were evaluated morphologically and immunocytochemically, using MyHC specific antibodies, as well as functionally using patch clamp electrophysiology to measure ion channel activity. Results indicated the establishment of the rapid expression of adult myosin isoforms that contrasts to their slow development in embryonic cultures. This culture system has applications in the understanding and treatment of age related muscle myopathy, muscular dystrophy, and for skeletal muscle engineering by providing a more relevant phenotype for both in vitro and in vivo applications. PMID:25683642

  13. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    NASA Astrophysics Data System (ADS)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  14. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  15. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults

    PubMed Central

    Hasegawa, Atsushi; Takahashi, Masahito; Satomi, Kazuhiko; Ohne, Hideaki; Takeuchi, Takumi; Sato, Shunsuke; Ichimura, Shoichi

    2016-01-01

    The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS) and Forelimb Locomotor Scale (FLS) and by measuring the range of motion (ROM) of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2 ± 24.7% in juvenile rats and 34.0 ± 19.8% in adult rats. FLS was 60.4 ± 26.8% in juvenile rats and 46.5 ± 26.9% in adult rats. ROM of the elbow and wrist were 88.9 ± 20.6% and 44.4 ± 24.1% in juvenile rats and 70.0 ± 29.2% and 40.0 ± 21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats. PMID:27065569

  16. Low Dose Parathyroid Hormone Maintains Normal Bone Formation in Adult Male Rats During Rapid Weight Loss

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

    A persistent negative energy balance results in bone loss. It is not clear whether the bone loss associated with chronic negative energy balance can be prevented. The objective of this study was to assess the efficacy of intermittent low dose parathyroid hormone (PTH) treatment in maintaining normal bone formation during severe energy restriction. Six-month-old male Fisher 344 rats were divided into 4 treatment groups: (1) baseline, (2) ad libitum (ad lib)-fed control, (3) energy-restricted (to consume 40% ad lib caloric intake), or (4) energy-restricted + low dose (1 μg/kg/d) PTH. Severe energy restriction for 14 days decreased body weight and serum leptin levels. Compared to ad lib-fed controls, energy-restricted rats had lower cancellous bone formation, higher osteoclast perimeter/bone perimeter and higher bone marrow adiposity in the proximal tibial metaphysis. Also, the energy-restricted rats had a lower periosteal bone formation rate at the tibia-fibula synostosis. Administration of PTH to energy-restricted rats had no effect on weight loss or osteoclast perimeter/bone perimeter. In contrast, energy-restricted rats treated with PTH had higher rates of cancellous and cortical bone formation compared to energy-restricted rats, and did not differ from the ad lib-fed control animals. Furthermore, PTH treatment maintained normal bone marrow adiposity. In conclusion, rapid weight loss in adult male rats was accompanied by decreased bone formation and increased bone marrow adiposity and these changes were prevented by low dose PTH treatment. Taken together, the results suggest that the energy cost of bone formation in adult rats is low and PTH therapy is effective in preventing the reduced bone formation associated with rapid weight loss. PMID:21215827

  17. Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats

    PubMed Central

    Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha’on, Ubon

    2015-01-01

    Background The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology. Methods Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets. Results MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated. Conclusion Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account. PMID:26121281

  18. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity. PMID:18679812

  19. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression.

    PubMed

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V; Christiansen, Sofie; Christensen, Trine; Andreasen, Jesper T; Palme, Rupert; Lichota, Jacek; Wiborg, Ove

    2012-12-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant tendency towards higher total cytosine methylation in rats from low maternal care dams. Assessment of methylation in the resilient versus anhedonic-like rat phenotypes, revealed only minor differences. Thus, maternal care status seems to be a strong predictor or trait marker for the behavioural phenotype. PMID:23075705

  20. Comparison of skull and femur lead levels in adult rats

    SciTech Connect

    Denton, J.E.; Potter, G.D.; Santolucito, J.A.

    1980-12-01

    The purpose of the study was to elucidate the relationship between skull and femur lead levels in laboratory rats. Forty-eight female rats were given one of four lead chloride drinking water solutions: 0.05, 0.58, 17, or 352 ppM lead. Two animals from each group were sacrificed after 3, 6, 9, 12, 15, and 24 weeks of treatment. Both femurs and the frontal and parietal bones of the skull were removed from each animal and analyzed for lead concentration by atomic absorption spectroscopy. A significant accumulation of lead was observed in femurs and skull bones only from animals in the 352 ppM lead treatment group. The lead concentrations of the femurs were significantly higher than skull lead concentrations for all groups and this relationship was described using a linear regression equation.

  1. Neurochemical and cellular specializations in the mammalian neocortex reflect phylogenetic relationships: evidence from primates, cetaceans, and artiodactyls.

    PubMed

    Hof, P R; Glezer, I I; Nimchinsky, E A; Erwin, J M

    2000-06-01

    Most of the available data on the cytoarchitecture of the cerebral cortex in mammals rely on Nissl, Golgi, and myelin stains and few studies have explored the differential morphologic and neurochemical phenotypes of neuronal populations. In addition, the majority of studies addressing the distribution and morphology of identified neuronal subtypes have been performed in common laboratory animals such as the rat, mouse, cat, and macaque monkey, as well as in postmortem analyses in humans. Several neuronal markers, such as neurotransmitters or structural proteins, display a restricted cellular distribution in the mammalian brain, and recently, certain cytoskeletal proteins and calcium-binding proteins have emerged as reliable markers for morphologically distinct subpopulations of neurons in a large number of mammalian species. In this article, we review the morphologic characteristics and distribution of three calcium-binding proteins, parvalbumin, calbindin, and calretinin, and of the neurofilament protein triplet, a component of the neuronal cytoskeleton, to provide an overview of the presence and cellular typology of these proteins in the neocortex of various mammalian taxa. Considering the remarkable diversity in gross morphological patterns and neuronal organization that occurred during the evolution of mammalian neocortex, the distribution of these neurochemical markers may help define taxon-specific patterns. In turn, such patterns can be used as reliable phylogenetic traits to assess the degree to which neurochemical specialization of neurons, as well as their regional and laminar distribution in the neocortex, represent derived or ancestral features, and differ in certain taxa from the laboratory species that are most commonly studied. PMID:10971015

  2. Altered activity in the central medial thalamus precedes changes in the neocortex during transitions into both sleep and propofol anesthesia.

    PubMed

    Baker, Rowan; Gent, Thomas C; Yang, Qianzi; Parker, Susan; Vyssotski, Alexei L; Wisden, William; Brickley, Stephen G; Franks, Nicholas P

    2014-10-01

    How general anesthetics cause loss of consciousness is unknown. Some evidence points toward effects on the neocortex causing "top-down" inhibition, whereas other findings suggest that these drugs act via subcortical mechanisms, possibly selectively stimulating networks promoting natural sleep. To determine whether some neuronal circuits are affected before others, we used Morlet wavelet analysis to obtain high temporal resolution in the time-varying power spectra of local field potentials recorded simultaneously in discrete brain regions at natural sleep onset and during anesthetic-induced loss of righting reflex in rats. Although we observed changes in the local field potentials that were anesthetic-specific, there were some common changes in high-frequency (20-40 Hz) oscillations (reductions in frequency and increases in power) that could be detected at, or before, sleep onset and anesthetic-induced loss of righting reflex. For propofol and natural sleep, these changes occur first in the thalamus before changes could be detected in the neocortex. With dexmedetomidine, the changes occurred simultaneously in the thalamus and neocortex. In addition, the phase relationships between the low-frequency (1-4 Hz) oscillations in thalamic nuclei and neocortical areas are essentially the same for natural sleep and following dexmedetomidine administration, but a sudden change in phase, attributable to an effect in the central medial thalamus, occurs at the point of dexmedetomidine loss of righting reflex. Our data are consistent with the central medial thalamus acting as a key hub through which general anesthesia and natural sleep are initiated. PMID:25274812

  3. The mammalian neocortex new pyramidal neuron: a new conception

    PubMed Central

    Marín-Padilla, Miguel

    2014-01-01

    The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex subplate zone). From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating its developing motor activities. The new pyramidal neuron’ distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface) without losing its original attachment to first layer or the location of its soma and, hence, retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs two pyramidal cell functional strata to carry out all its motor activities, the mouse 3, cat 4, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing and thinking as a premotor activity. Words used in language are the motor expression of thoughts and represent sounds produced by maneuvering the column of expiratory

  4. Evolution of the neocortex: a perspective from developmental biology.

    PubMed

    Rakic, Pasko

    2009-10-01

    The enlargement and species-specific elaboration of the cerebral neocortex during evolution holds the secret to the mental abilities of humans; however, the genetic origin and cellular mechanisms that generated the distinct evolutionary advancements are not well understood. This article describes how novelties that make us human may have been introduced during evolution, based on findings in the embryonic cerebral cortex in different mammalian species. The data on the differences in gene expression, new molecular pathways and novel cellular interactions that have led to these evolutionary advances may also provide insight into the pathogenesis and therapies for human-specific neuropsychiatric disorders. PMID:19763105

  5. 532 nm Low-Power Laser Irradiation Facilitates the Migration of GABAergic Neural Stem/Progenitor Cells in Mouse Neocortex

    PubMed Central

    Fukuzaki, Yumi; Shin, Hyeryun; Kawai, Hideki D.; Yamanoha, Banri; Kogure, Shinichi

    2015-01-01

    Background and Objective Accumulating evidence has shown that low-power laser irradiation (LLI) affects cell proliferation and survival, but little is known about LLI effects on neural stem/progenitor cells (NSPCs). Here we investigate whether transcranial 532 nm LLI affects NSPCs in adult murine neocortex and in neurospheres from embryonic mice. Study Design/Materials and Methods We applied 532 nm LLI (Nd:YVO4, CW, 60 mW) on neocortical surface via cranium in adult mice and on cultured cells from embryonic mouse brains in vitro to investigate the proliferation and migration of NSPCs and Akt expression using immunohistochemical assays and Western blotting techniques. Results In vivo experiments demonstrated that 532 nm LLI significantly facilitated the migration of GABAergic NSPCs that were induced to proliferate in layer 1 by mild ischemia. In vitro experiments using GABAergic NSPCs derived from embryonic day 14 ganglionic eminence demonstrated that 532 nm LLI for 60 min promoted the migration of GAD67-immunopositive NSPCs with a significant increase of Akt expression. Meanwhile, the LLI induced proliferation, but not migration, of NSPCs that give rise to excitatory neurons. Conclusion It is concluded that 532 nm LLI promoted the migration of GABAergic NSPCs into deeper layers of the neocortex in vivo by elevating Akt expression. PMID:25919297

  6. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  7. Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

    SciTech Connect

    Norton, S.

    1986-04-01

    Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation.

  8. Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

    PubMed

    Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

    2011-10-10

    Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test. PMID:21645557

  9. TESTOSTERONE AND SOCIAL ISOLATION INFLUENCE ADULT NEUROGENESIS IN THE DENTATE GYRUS OF MALE RATS

    PubMed Central

    Spritzer, Mark D.; Ibler, Erin; Inglis, William; Curtis, Molly G.

    2011-01-01

    Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): 1) sham/pair-housed, 2) sham/isolated, 3) castrate/pair-housed, and 4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n =8/group): 1) oil/pair-housed, 2) oil/isolated, 3) testosterone/pair-housed, and 4) testosterone/isolated. All rats were injected with 5-Bromo-2’-deoxyuridine (BrdU, 200 mg/kg body mass) and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and sub-granular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating levels of

  10. Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats.

    PubMed

    Spritzer, M D; Ibler, E; Inglis, W; Curtis, M G

    2011-11-10

    Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): (1) sham/pair-housed, (2) sham/isolated, (3) castrate/pair-housed, and (4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated, and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n=8/group): (1) oil/pair-housed, (2) oil/isolated, (3) testosterone/pair-housed, and (4) testosterone/isolated. All rats were injected with 5-bromo-2'-deoxyuridine (BrdU, 200 mg/kg body mass), and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and subgranular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating

  11. Prenatal genesis of layer II doublecortin expressing neurons in neonatal and young adult guinea pig cerebral cortex

    PubMed Central

    Yang, Yan; Xie, Mi-Xin; Li, Jian-Ming; Hu, Xia; Patrylo, Peter R.; Luo, Xue-Gang; Cai, Yan; Li, Zhiyuan; Yan, Xiao-Xin

    2015-01-01

    Cells expressing doublecortin (DCX+) occur at cortical layer II, predominantly over the paleocortex in mice/rats, but also across the neocortex among larger mammals. Here, we explored the time of origin of these cells in neonatal and 2-month-old guinea pigs following prenatal BrdU pulse-chasing. In the neocortex, BrdU+ cells birth-dated at embryonic day 21 (E21), E28, and E35 laminated over the cortical plate with an inside-out order. In the piriform cortex, cells generated at E21 and E28 occurred with a greater density in layer II than III. Many cells were generated at later time points until birth, occurring in the cortex without a laminar preference. DCX+ cells in the neocortex and piriform cortex partially co-colocalized with BrdU (up to 7.5%) in the newborns after pulse-chasing from E21 to E49 and in the 2 month-old animals after pulse-chasing from E28 to E60/61, with higher rates seen among the E21-E35 groups. Together, layer II DCX+ cells in neonatal and young adult guinea pigs may be produced over a wide prenatal time window, but mainly during the early phases of corticogenesis. Our data also show an earlier establishment of the basic lamination in the piriform relative to neocortical areas in guinea pigs. PMID:26321922

  12. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    PubMed

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

  13. Testosterone influences spatial strategy preferences among adult male rats

    PubMed Central

    Spritzer, Mark D.; Fox, Elliott C.; Larsen, Gregory D.; Batson, Christopher G.; Wagner, Benjamin A.; Maher, Jack

    2013-01-01

    Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. PMID:23597827

  14. B-cell production and differentiation in adult rats.

    PubMed Central

    Bazin, H; Platteau, B; Maclennan, I C; Johnson, G D

    1985-01-01

    The B-cell development in a group of rats was suppressed for the first 45 days of life by serial administration of rabbit anti-rat IgM and IgD antibody. Total or near total suppression of B lymphopoiesis was achieved. At 45 days, suppression was stopped by injection of IgM and IgD rat paraproteins. The sequence of B-cell and plasma cell development following suppression was assessed by immunohistological analysis of spleen lymph nodes and small intestinal lamina propria. The main findings are listed below. Complete reconstitution of B-cell numbers occurs within 8 days, at which stage germinal centres are also present. B lymphopoiesis in the red pulp of the spleen differs from that reported for bone marrow. Cells develop expressing surface sIgM and sIgM with IgA, but not sIgD. sIgD-positive cells first appear in splenic follicles 2 days after stopping suppression, but their appearance in lymph nodes is delayed until after 3 days. At this stage, sIgD-positive cells become apparent in the splenic red pulp. IgM plasma cells appear from day 4. IgA plasma cells in the gut appear in small numbers at day 6, and gradually increase to normal numbers by day 14. sIgG2c expression in the splenic marginal zone did not approach normal levels, even 2 weeks after suppression was stopped. Images Figure 4 Figure 2 Figure 3 PMID:3871730

  15. Maternal Undernutrition Induces Premature Reproductive Senescence in Adult Female Rat Offspring

    PubMed Central

    Khorram, Omid; Keen-Rinehart, Erin; Chuang, Tsai-Der; Ross, Michael G.; Desai, Mina

    2014-01-01

    Objective To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring. Design Animal (rat) study. Setting Research Laboratory. Animals Female Sprague-Dawley rats. Intervention(s) Food restriction during the second half of pregnancy in rats. Main Outcome Measures Circulating gonadotropins, Anti-Mullerian Hormone (AMH), ovarian morphology, estrous cyclicity and gene expression studies in the hypothalamus and ovary in 1 day old (P1) and aging adult offspring. Results Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating testosterone (T), increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma Leuteinizing (LH/)/Follicle Stimulating hormone (FSH) levels, reduced estradiol (E2) levels and no changes in AMH in adult LBW offspring compared to control offspring. Hypothalamic expression of leptin receptor (OBRb), estrogen receptor-α (ER-α) and Gonadotropin Releasing hormone (GnRH) protein were altered in an age-dependent manner with increased ObRb, ER-α expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami. Conclusion Our data indicates that the maternal nutritional environment programs reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to development of obesity and hyperleptinemia in these animals in adult life. PMID:25439841

  16. Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats.

    PubMed

    Gellner, Candice A; Belluzzi, James D; Leslie, Frances M

    2016-10-01

    Although smoking initiation typically occurs during adolescence, most preclinical studies of tobacco use involve adult animals. Furthermore, their focus is largely on nicotine alone, even though cigarette smoke contains thousands of constituents. The present study therefore aimed to determine whether aqueous constituents in cigarette smoke affect acquisition of nicotine self-administration during adolescence in rats. Adolescent and adult male rats, aged postnatal day (P) 25 and 85, respectively, were food trained on a fixed ratio 1 (FR1) schedule, then allowed to self-administer one of 5 doses of nicotine (0, 3.75, 7.5, 15, or 30 μg/kg) or aqueous cigarette smoke extract (CSE) with equivalent nicotine content. Three progressively more difficult schedules of reinforcement, FR1, FR2, and FR5, were used. Both adolescent and adult rats acquired self-administration of nicotine and CSE. Nicotine and CSE similarly increased non-reinforced responding in adolescents, leading to enhanced overall drug intake as compared to adults. When data were corrected for age-dependent alterations in non-reinforced responding, adolescents responded more for low doses of nicotine and CSE than adults at the FR1 reinforcement schedule. No differences in adolescent responding for the two drugs were seen at this schedule, whereas adults had fewer responses for CSE than for nicotine. However, when the reinforcement schedule was increased to FR5, animals dose-dependently self-administered both nicotine and CSE, but no drug or age differences were observed. These data suggest that non-nicotine tobacco smoke constituents do not influence the reinforcing effect of nicotine in adolescents. PMID:27346207

  17. DISTRIBUTION OF [14C]ETHANE DIMENTHANESULFONATE IN IMMATURE AND ADULT MALE RATS FOLLOWING AN ACUTE EXPOSURE

    EPA Science Inventory

    In the adult rat, ethane dimethanesulphonate (EDS) reduces testosterone (T) production by killing Leydig cells. Studies have also shown that acute EDS administration produces transient infertility and epididymal effects. Although these later effects were believed to be indirect r...

  18. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty.

    PubMed

    Mendes, Talita Biude; Paccola, Camila Cicconi; de Oliveira Neves, Flávia Macedo; Simas, Joana Noguères; da Costa Vaz, André; Cabral, Regina Elisabeth L; Vendramini, Vanessa; Miraglia, Sandra Maria

    2016-07-01

    The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood. PMID:27069006

  19. Origin and evolution of developmental enhancers in the mammalian neocortex.

    PubMed

    Emera, Deena; Yin, Jun; Reilly, Steven K; Gockley, Jake; Noonan, James P

    2016-05-10

    Morphological innovations such as the mammalian neocortex may involve the evolution of novel regulatory sequences. However, de novo birth of regulatory elements active during morphogenesis has not been extensively studied in mammals. Here, we use H3K27ac-defined regulatory elements active during human and mouse corticogenesis to identify enhancers that were likely active in the ancient mammalian forebrain. We infer the phylogenetic origins of these enhancers and find that ∼20% arose in the mammalian stem lineage, coincident with the emergence of the neocortex. Implementing a permutation strategy that controls for the nonrandom variation in the ages of background genomic sequences, we find that mammal-specific enhancers are overrepresented near genes involved in cell migration, cell signaling, and axon guidance. Mammal-specific enhancers are also overrepresented in modules of coexpressed genes in the cortex that are associated with these pathways, notably ephrin and semaphorin signaling. Our results also provide insight into the mechanisms of regulatory innovation in mammals. We find that most neocortical enhancers did not originate by en bloc exaptation of transposons. Young neocortical enhancers exhibit smaller H3K27ac footprints and weaker evolutionary constraint in eutherian mammals than older neocortical enhancers. Based on these observations, we present a model of the enhancer life cycle in which neocortical enhancers initially emerge from genomic background as short, weakly constrained "proto-enhancers." Many proto-enhancers are likely lost, but some may serve as nucleation points for complex enhancers to evolve. PMID:27114548

  20. Origin and evolution of developmental enhancers in the mammalian neocortex

    PubMed Central

    Emera, Deena; Yin, Jun; Reilly, Steven K.; Gockley, Jake; Noonan, James P.

    2016-01-01

    Morphological innovations such as the mammalian neocortex may involve the evolution of novel regulatory sequences. However, de novo birth of regulatory elements active during morphogenesis has not been extensively studied in mammals. Here, we use H3K27ac-defined regulatory elements active during human and mouse corticogenesis to identify enhancers that were likely active in the ancient mammalian forebrain. We infer the phylogenetic origins of these enhancers and find that ∼20% arose in the mammalian stem lineage, coincident with the emergence of the neocortex. Implementing a permutation strategy that controls for the nonrandom variation in the ages of background genomic sequences, we find that mammal-specific enhancers are overrepresented near genes involved in cell migration, cell signaling, and axon guidance. Mammal-specific enhancers are also overrepresented in modules of coexpressed genes in the cortex that are associated with these pathways, notably ephrin and semaphorin signaling. Our results also provide insight into the mechanisms of regulatory innovation in mammals. We find that most neocortical enhancers did not originate by en bloc exaptation of transposons. Young neocortical enhancers exhibit smaller H3K27ac footprints and weaker evolutionary constraint in eutherian mammals than older neocortical enhancers. Based on these observations, we present a model of the enhancer life cycle in which neocortical enhancers initially emerge from genomic background as short, weakly constrained “proto-enhancers.” Many proto-enhancers are likely lost, but some may serve as nucleation points for complex enhancers to evolve. PMID:27114548

  1. Organization of sensory neocortex in prairie voles (Microtus ochrogaster).

    PubMed

    Campi, Katharine L; Karlen, Sarah J; Bales, Karen L; Krubitzer, Leah

    2007-05-20

    In the current investigation, the functional organization of visual, auditory, and somatosensory cortex was examined in prairie voles (Microtus ochrogaster) by using electrophysiological recording techniques. Functional boundaries of cortical fields were directly related to myeloarchitectonic boundaries. Our results demonstrated that most of the neocortex is occupied by the visual, auditory, and somatosensory areas. Specifically, a small area 17, or primary visual area (V1), was located on the caudomedial pole of the neocortex; a large auditory cortex (AC), which contains the primary auditory area (A1) and other auditory fields, encompassed almost the entire temporal pole; and a large area 3b, or primary somatosensory area (S1), contained a complete representation of the contralateral body surface. Furthermore, these areas were coextensive with distinct myeloarchitectonic appearances. We also observed that the AC appeared to be disproportionately large in the prairie vole compared with other rodents. In addition, we found that both primary and nonprimary areas contained neurons that responded to auditory stimulation. Finally, we observed within S1 a disproportionate amount of cortex that was devoted to representing the perioral hairs and the snout and also that neurons within this representation had very small receptive fields. We discuss the expanded auditory domain and the enlarged representation of perioral hairs as they relate to the specialized life style of the prairie vole. PMID:17366609

  2. Effect of dietary caffeine and theophylline on urinary calcium excretion in the adult rat.

    PubMed

    Whiting, S J; Whitney, H L

    1987-07-01

    The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and 450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate, sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of theophylline (1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least 22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine feeding may result from a prostaglandin-mediated process distinct from diuresis. PMID:3612301

  3. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    SciTech Connect

    Gorban', E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  4. Effects of 4-Vinylcyclohexene Diepoxide on Peripubertal and Adult Sprague–Dawley Rats: Ovarian, Clinical, and Pathologic Outcomes

    PubMed Central

    Muhammad, F Salih; Goode, Amanda K; Kock, Nancy D; Arifin, Esther A; Cline, J Mark; Adams, Michael R; Hoyer, Patricia B; Christian, Patricia J; Isom, Scott; Kaplan, Jay R; Appt, Susan E

    2009-01-01

    Young rats treated daily with intraperitoneal 4-vinylcyclohexene diepoxide (VCD) undergo selective destruction of primordial follicles, resulting in gradual ovarian failure resembling the menopausal transition in women. To determine whether VCD has similar effects on ovaries of older rats, adult and peripubertal Sprague–Dawley rats were injected intraperitoneally daily for 30 d with vehicle or VCD at 40 or 80 mg/kg. Body weight, food intake, complete blood counts, and markers of liver injury and renal function were measured during VCD treatment. Complete gross necropsy and microscopic observations were performed on day 31, and ovarian follicles were counted. At 80 mg/kg, VCD destroyed primordial and primary follicles to a similar extent in both adult and peripubertal animals, although adult rats likely started with fewer follicles and therefore approached follicle depletion. Treatment with VCD did not affect body weight, but food intake was reduced in both adult and peripubertal rats treated with 80 mg/kg VCD. Adult rats treated with 80 mg/kg VCD had neutrophilia and increased BUN and creatinine; in addition, 4 of these rats were euthanized on days 25 or 26 due to peritonitis. VCD treatment did not increase alanine aminotransferase levels, a marker of liver injury, although the 80-mg/kg dose increased liver weights. In conclusion, VCD effectively destroys small preantral follicles in adult Sprague–Dawley rats, making them a suitable model of the menopausal transition of women. However, because adult rats were more sensitive to the irritant properties of VCD, the use of a lower dose should be considered. PMID:19295054

  5. Effects of 4-vinylcyclohexene diepoxide on peripubertal and adult Sprague-Dawley rats: ovarian, clinical, and pathologic outcomes.

    PubMed

    Muhammad, F Salih; Goode, Amanda K; Kock, Nancy D; Arifin, Esther A; Cline, J Mark; Adams, Michael R; Hoyer, Patricia B; Christian, Patricia J; Isom, Scott; Kaplan, Jay R; Appt, Susan E

    2009-02-01

    Young rats treated daily with intraperitoneal 4-vinylcyclohexene diepoxide (VCD) undergo selective destruction of primordial follicles, resulting in gradual ovarian failure resembling the menopausal transition in women. To determine whether VCD has similar effects on ovaries of older rats, adult and peripubertal Sprague-Dawley rats were injected intraperitoneally daily for 30 d with vehicle or VCD at 40 or 80 mg/kg. Body weight, food intake, complete blood counts, and markers of liver injury and renal function were measured during VCD treatment. Complete gross necropsy and microscopic observations were performed on day 31, and ovarian follicles were counted. At 80 mg/kg, VCD destroyed primordial and primary follicles to a similar extent in both adult and peripubertal animals, although adult rats likely started with fewer follicles and therefore approached follicle depletion. Treatment with VCD did not affect body weight, but food intake was reduced in both adult and peripubertal rats treated with 80 mg/kg VCD. Adult rats treated with 80 mg/kg VCD had neutrophilia and increased BUN and creatinine; in addition, 4 of these rats were euthanized on days 25 or 26 due to peritonitis. VCD treatment did not increase alanine aminotransferase levels, a marker of liver injury, although the 80-mg/kg dose increased liver weights. In conclusion, VCD effectively destroys small preantral follicles in adult Sprague-Dawley rats, making them a suitable model of the menopausal transition of women. However, because adult rats were more sensitive to the irritant properties of VCD, the use of a lower dose should be considered. PMID:19295054

  6. Airborne particles of the california central valley alter the lungs of healthy adult rats.

    PubMed Central

    Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

    2003-01-01

    Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

  7. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    NASA Astrophysics Data System (ADS)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  8. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects. PMID:20395146

  9. REPRODUCTIVE TOXICITY OF A SINGLE DOSE OF 1,3-DINITROBENZENE IN TWO AGES OF YOUNG ADULT MALE RATS

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-Dinitrobenzene (M-DNB). oung adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, ...

  10. EFFECTS OF ETHANE DIMETHANESULFONATE (EDS) ON ADULT AND IMMATURE RABBIT LEYDIG CELLS: COMPARISON WITH EDS-TREATED RAT LEYDIG CELLS

    EPA Science Inventory

    Ethane-dimethanesulfonate (EDS) has been shown to selectively kill Leydig cells and depress testosterone production in adult rats. ecent study has shown that immature rat leydig cells are less sensitive to EDS exposure. here is evidence that the rabbit metabolizes EDS to methane ...

  11. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  12. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  13. Higher white adipocyte area and lower leptin production in adult rats overfed during lactation.

    PubMed

    Conceição, E P S; Trevenzoli, I H; Oliveira, E; Franco, J G; Carlos, A S; Nascimento-Saba, C C A; Moura, E G; Lisboa, P C

    2011-06-01

    Litter size reduction during lactation is a good model for childhood obesity since it induces overnutrition and programming for obesity at adulthood. Adult offspring develop higher fat mass content, hyperinsulinemia and insulin resistance, hypertension, lower HDL cholesterol, hyperphagia, and leptin resistance. Leptin resistance is often associated with hyperleptinemia. Although we observed higher SOCS3 and lower STAT3 in the hypothalamus of rats raised in small litters featuring a central leptin resistance, they showed unexpected normoleptinemia at 180 days old. Then, to clarify why early overfed rats did not develop hyperleptinemia when adult, we studied the leptin production by the visceral and subcutaneous adipose tissue and skeletal muscle as well as the morphology in the 2 different fat depots. To induce EO, litter size was reduced to 3 pups/litter (SL group) on the 3 (rd) day of life. In controls (NL group), litter size was adjusted to 10 pups/litter. Rats were killed at 180 days old. The programming of adipose tissue morphology by early overnutrition is specific between the different fat depots with hypertrophy only in the visceral compartment. In addition, the visceral adipocyte showed lower leptin content that may indicate a reduced leptin synthesis. These data suggest that adipocytes from SL rats are dysfunctional, since a higher leptin production in larger adipose cells is expected. In conclusion, postnatal nutrition is determinant for future leptin production by different fat depots as well as adipocyte morphology. These changes seem to be related to the severity of obesity and its metabolic consequences. PMID:21512961

  14. AGE-DEPENDENT MDPV-INDUCED TASTE AVERSIONS AND THERMOREGULATION IN ADOLESCENT AND ADULT RATS

    PubMed Central

    Merluzzi, Andrew P.; Hurwitz, Zachary E.; Briscione, Maria A.; Cobuzzi, Jennifer L.; Wetzell, Bradley; Rice, Kenner C.; Riley, Anthony L.

    2013-01-01

    Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of “bath salts,” the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8 or 3.2 mg/kg), a common constituent in “bath salts,” in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population. PMID:24122728

  15. A spaceflight study of synaptic plasticity in adult rat vestibular maculas

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1994-01-01

    Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but

  16. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

    PubMed

    Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

    2016-06-01

    Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. PMID:27036327

  17. Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

    PubMed

    Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

    2016-05-01

    Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

  18. Properties of ionic currents from isolated adult rat carotid body chemoreceptor cells: effect of hypoxia.

    PubMed Central

    López-López, J R; González, C; Pérez-García, M T

    1997-01-01

    1. The electrical properties of chemoreceptor cells from neonatal rat and adult rabbit carotid bodies (CBs) are strikingly different. These differences have been suggested to be developmental and/or species related. To distinguish between the two possibilities, the whole-cell configuration of the patch-clamp technique was used to characterize the ionic currents present in isolated chemoreceptor cells from adult rat CBs. Since hypoxia-induced inhibition of O2-sensitive K+ currents is considered a crucial step in O2 chemoreception, the effect of hypoxia on the adult rat chemoreceptor cell currents was also studied. 2. Outward currents were carried mainly by K+, and two different components could be distinguished: a Ca(2+)-dependent K+ current (IK(Ca)) sensitive to Cd2+ and charybdotoxin (CTX), and a Ca(2+)-insensitive, voltage-dependent K+ current (IK(V)). IK(V) showed a slow voltage-dependent activation (time constant (tau) of 87.4 ms at -20 mV and 8.8 ms at +60 mV) and a very slow inactivation, described by the sum of two exponentials (tau 1 = 684 +/- 150 ms and tau 2 = 4.96 +/- 0.76 s at + 30 mV), that was almost voltage insensitive. The kinetic and pharmacological properties of IK(V) are typical of a delayed rectifier K+ channel. 3. Voltage-dependent Ca2+ currents (ICa) were present in nineteen of twenty-seven cells. TTX-sensitive Na+ currents were also observed in about 10% of the cells. 4. Low PO2 (< 10 mmHg) reduced the whole outward current amplitude by 22.17 +/- 1.96% (n = 27) at +20 mV. This effect was absent in the presence of Cd2+. Since low PO2 did not affect ICa, we conclude that hypoxia selectively blocks IK(Ca). 5. The properties of the currents recorded in adult rat chemoreceptor cells, including the specific inhibition of IK(Ca) by hypoxia, are similar to those reported in neonatal rat CB cells, implying that the differences between rat and rabbit chemoreceptor cells are species related. PMID:9080372

  19. Sympathectomy alters bone architecture in adult growing rats.

    PubMed

    Pagani, F; Sibilia, V; Cavani, F; Ferretti, M; Bertoni, L; Palumbo, C; Lattuada, N; De Luca, E; Rubinacci, A; Guidobono, F

    2008-08-15

    Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone. PMID:18449939

  20. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain. PMID:25939577

  1. Early deprivation reduced anxiety and enhanced memory in adult male rats.

    PubMed

    Zhang, Xuliang; Wang, Bo; Jin, Jing; An, Shuming; Zeng, Qingwen; Duan, Yanhong; Yang, Liguo; Ma, Jing; Cao, Xiaohua

    2014-09-01

    The effects of early deprivation (ED, which involves both dam and littermate deprivation) on anxiety and memory are less investigated in comparison with maternal separation (MS), and it is not yet clear how ED affects long-term potentiation (LTP) in the hippocampal Schaffer collateral pathway. By using a series of behavioral tests, enzyme-linked immunosorbent assay and field potential recording, we explored the effect of pre-weaning daily 3-h ED on anxiety, memory and potential mechanisms in adult male rats. Compared with control, ED rats spent longer time in open arms of elevated plus maze and in light compartment of light-dark transition box. Consistently, stress-induced blood plasma corticosterone level was also lower in ED rats. Moreover, ED rats showed better performance in social recognition and Morris water maze test. In accordance with results in memory tests, the threshold of LTP induction in hippocampal CA3-CA1 pathway of ED rats was also reduced. Our results indicate ED reduced anxiety, but enhanced social recognition and spatial reference memory. We suggest the diminished hypothalamic-pituitary-adrenal axis response and facilitated hippocampal LTP may contribute to the anxiety-reducing and memory-enhancing effects of ED, respectively. PMID:25157962

  2. Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

    PubMed

    Asker, M E; Hassan, W A; El-Kashlan, A M

    2015-08-01

    The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress. PMID:25220112

  3. Effect of restraint and copper deficiency on blood pressure and mortality of adult rats

    SciTech Connect

    Klevay, L.M.; Halas, E.S. )

    1989-02-01

    The etiology of most hypertension is unknown; stress is thought to elevate blood pressure. Male, weanling Sprague-Dawley rats were fed a purified diet plus a drinking solution containing 10{mu}g Zn and 2{mu}g Cu/ml (acetate sulfate, respectively). Systolic blood pressure was measured without anesthesia. After being matched by mean weight (280g) and blood pressure into 4 groups of 15, groups 1 and 2 received a drinking solution without copper. After 24 days rats in groups 2 and 4 were restrained for 45 min. daily (A.M.) for 23 days in a small plastic cage (19{times}6{times}6 cm). Final pressures were affected both by stress and dietary Cu: group 1, 119; group 2, 131; group 3, 114; group 4, 123 mm Hg. One rat in each of groups 1, 3, 4 and 10 rats in group 2, died. Among these latter hemorrhage was prominent, blood being found in bladder (2), gut (2), peritoneum (2) and scrotum (1). Copper deficiency decreased cooper in both adrenal gland and liver by 58% and in heart by 29% restraint was without effect. Cardiac sodium was increased 6% only by deficiency. Results confirm the hypertensive effect of copper deficiency in adult rats and reveal that the stress of restraint increases blood pressure. Copper deficiency plus stress is harmful.

  4. Differential expression of TRPM7 in rat hepatoma and embryonic and adult hepatocytes.

    PubMed

    Lam, D Hung; Grant, Caroline E; Hill, Ceredwyn E

    2012-04-01

    TRPM7 channels are implicated in cellular survival, proliferation, and differentiation. However, a profile of TRPM7 activity in a specific cell type has not been determined from embryonic to terminally differentiated state. Here, we characterized TRPM7 expression in a spectrum of rat liver cells at different developmental stages. Using the whole-cell patch clamp technique, TRPM7-like Na(+) currents were identified in RLC-18 cells, a differentiated, proliferating hepatocellular line derived from day 17 embryonic rat liver. Currents were outwardly rectifying, enhanced in divalent-free solutions, and inhibited by intracellular Mg(2+). Reverse transcription - polymerase chain reaction (RT-PCR) revealed that RLC-18 cells express both TRPM6 and TRPM7. However, mean currents were reduced almost 80% by 1 mmol/L 2-aminoethoxyphenylborate (2-APB) and were abolished in RLC-18 cells heterologously expressing a dominant negative TRPM7 construct, suggesting that TRPM7 is the major current carrier in these cells. Functional comparison showed that relative to terminally differentiated adult rat hepatocytes, currents were 1.8 and 3.9 times higher in, respectively, RLC-18 and WIF-B cells, a rat hepatoma - human fibroblast cross. Our results demonstrate that plasma membrane TRPM7 channels are more highly expressed in proliferating cells as compared with terminally differentiated and nondividing rat hepatocytes and suggest that downregulation of this channel is associated with hepatocellular differentiation. PMID:22429021

  5. Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition.

    PubMed

    Mellough, Carla B; Cho, Seongeun; Wood, Andrew; Przyborski, Stefan

    2011-09-01

    Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS. PMID:21256909

  6. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  7. Differential Effects of Inhaled Toluene on Locomotor Activity in Adolescent and Adult Rats

    PubMed Central

    Batis, Jeffery C.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8,000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm “air” controls at both ages. These changes depended upon when activity was measured – during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the “recovery” period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen

  8. Alterations in cytochrome P-450 levels in adult rats following neonatal exposure to xenobiotics

    SciTech Connect

    Zangar, R.C. Pacific Northwest Laboratories, Richland, WA ); Springer, D.L. ); Buhler, D.R. )

    1993-01-01

    Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long-term changes in enzyme regulation. Previously, the authors have observed changes in adult testosterone metabolism and in cytochrome P-450 (P-450) mRNA levels in animals neonatally exposed to phenobarbital (PB) or diethylstilbestrol (DES). In order to test for other enzyme alterations, they used Western blot procedures for specific P-450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12-dimethylbenz[a]anthracene (DMBA), or pregnenolone 16[alpha]-carbonitrile (PCN). The most striking effects were observed in the DES-treated males: P-4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P-4503A2 was decreased by 44%. No changes were observed in the DES-treated males in levels of P-4502E1, P-4502B, or the male-specific P-4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti-P4502B-reactive protein without significant changes in the other enzymes. The DES- and DMBA-treated females had increased levels of the female-specific P-4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P-450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two-thirds lower dose. 37 refs., 5 figs.

  9. The distribution and localization of /sup 127/m tellurium in normal and pathological nervous tissues of young and adult rats

    SciTech Connect

    Duckett, S.

    1982-11-01

    An equal amount (per weight) of /sup 127/m tellurium (Te) was injected IP into weanling and adult rats, some intoxicated with a diet containing Te, others not. The young intoxicated rats presented a segmental demyelination of the sciatic nerve and paralysis of the hind limbs; the adult intoxicated rats did not. Quantitation of 127m Te in nervous and other tissues was done with a gamma counter. Correlative morphological examination of the nervous tissues was done with light and electron microscopy. This study shows that Te crosses the vascular wall without injuring endothelial cells and invades the surrounding sciatic nerve parenchyma following administration of 127m Te to a weanling or adult rat. However, Te damages the endothelium, crosses the vascular wall of endo and perineurial vessels in weanling rats, causes a perivascular oedema, cytoplasmic anomalies in the Schwann cells, destruction of myelin and apparently invades axones--according to autoradiographic studies--following the administration of 127m Te plus the Te-diet. It is concluded that Te penetrates more quickly and in larger amounts the walls of blood vessels in the sciatic nerve of weanling rats intoxicated with Te, than the same nerve in the other weanling and adults rats. Te in the amounts indicated here penetrates the parenchyma of the CNS but apparently does not cause injury.

  10. Neocortical slices from adult chronic epileptic rats exhibit discharges of higher voltages and broader spread.

    PubMed

    Serafini, R; Dettloff, S; Loeb, J A

    2016-05-13

    Much of the current understanding of epilepsy mechanisms has been built on data recorded with one or a few electrodes from temporal lobe slices of normal young animals stimulated with convulsants. Mechanisms of adult, extratemporal, neocortical chronic epilepsy have not been characterized as much. A more advanced understanding of epilepsy mechanisms can be obtained by recording epileptiform discharges simultaneously from multiple points of an epileptic focus so as to define their sites of initiation and pathways of spreading. Brain slice recordings can characterize epileptic mechanisms in a simpler, more controlled preparation than in vivo. Yet, the intrinsic hyper-excitability of a chronic epileptic focus may not be entirely preserved in slices following the severing of connections in slice preparation. This study utilizes recordings of multiple electrode arrays to characterize which features of epileptic hyper-excitability present in in vivo chronic adult neocortical epileptic foci are preserved in brain slices. After tetanus toxin somatosensory cortex injections, adult rats manifest chronic spontaneous epileptic discharges both in the injection site (primary focus) and in the contralateral side (secondary focus). We prepared neocortical slices from these epileptic animals. When perfused with 4-Aminopyridine in a magnesium free medium, epileptic rat slices exhibit higher voltage discharges and broader spreading than control rat slices. Rates of discharges are similar in slices of epileptic and normal rats, however. Ictal and interictal discharges are distributed over most cortical layers, though with significant differences between primary and secondary foci. A chronic neocortical epileptic focus in slices does not show increased spontaneous pacemakers initiating epileptic discharges but shows discharges with higher voltages and broader spread, consistent with an enhanced synchrony of cellular and synaptic generators over wider surfaces. PMID:26892299

  11. Infrasound increases intracellular calcium concentration and induces apoptosis in hippocampi of adult rats.

    PubMed

    Liu, Zhaohui; Gong, Li; Li, Xiaofang; Ye, Lin; Wang, Bin; Liu, Jing; Qiu, Jianyong; Jiao, Huiduo; Zhang, Wendong; Chen, Jingzao; Wang, Jiuping

    2012-01-01

    In the present study, we determined the effect of infrasonic exposure on apoptosis and intracellular free Ca²⁺ ([Ca²⁺]i) levels in the hippocampus of adult rats. Adult rats were randomly divided into the control and infrasound exposure groups. For infrasound treatment, animals received infrasonic exposure at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and isolated hippocampal neurons were cultured. The [Ca²⁺]i levels in hippocampal neurons from adult rat brains were determined by Fluo-3/AM staining with a confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double staining. Positive cells were sorted and analyzed by flow cytometry. Elevated [Ca²⁺]i levels were observed on days 14 and 21 after rats received daily treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure (p<0.01 vs. control). The highest levels of [Ca²⁺]i were detected in the 130 dB SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was found to increase on day 7 following 90 dB SPL infrasound exposure, and significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis was first observed on day 14, whereas the number of apoptotic cells gradually decreased thereafter. Additionally, a marked correlation between cell apoptosis and [Ca²⁺]i levels was found on day 14 and 21 following daily treatment with 90 and 130 dB SPL, respectively. These results demonstrate that a period of infrasonic exposure induced apoptosis and upregulated [Ca²⁺]i levels in hippocampal neurons, suggesting that infrasound may cause damage to the central nervous system (CNS) through the Ca²⁺‑mediated apoptotic pathway in hippocampal neurons. PMID:21946944

  12. Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

    PubMed Central

    Friedman, LK; Slomko, AM; Wongvravit, JP; Naseer, Z; Hu, S; Wan, WY; Ali, SS

    2015-01-01

    Background and Purpose: The efficacy of retigabine (RGB), a positive allosteric modulator of K+ channels indicated for adjunct treatment of partial seizures, was studied in two adult models of kainic acid (KA)-induced status epilepticus to determine it’s toleratbility. Methods: Retigabine was administered systemiclly at high (5 mg/kg) and low (1–2 mg/kg) doses either 30 min prior to or 2 hr after KA-induced status epilepticus. High (1 µg/µL) and low (0.25 µg/µL) concentrations of RGB were also delivered by intrahippocampal microinjection in the presence of KA. Results: Dose-dependent effects of RGB were observed with both models. Lower doses increased seizure behavior latency and reduced the number of single spikes and synchronized burst events in the electroencephalogram (EEG). Higher doses worsened seizure behavior, produced severe ataxia, and increased spiking activity. Animals treated with RGB that were resistant to seizures did not exhibit significant injury or loss in GluR1 expression; however if stage 5–6 seizures were reached, typical hippocampal injury and depletion of GluR1 subunit protein in vulernable pyramidal fields occurred. Conclusions: RGB was neuroprotective only if seizures were significantly attenuated. GluR1 was simultaneously suppressed in the resistant granule cell layer in presence of RGB which may weaken excitatory transmission. Biphasic effects observed herein suggest that the human dosage must be carefully scrutinized to produce the optimal clinical response. PMID:26819936

  13. Taurine activates GABAergic networks in the neocortex of immature mice

    PubMed Central

    Sava, Bogdan A.; Chen, Rongqing; Sun, Haiyan; Luhmann, Heiko J.; Kilb, Werner

    2014-01-01

    Although it has been suggested that taurine is the main endogenous neurotransmitter acting on glycine receptors, the implications of glycine receptor-mediated taurine actions on immature neocortical networks have not been addressed yet. To investigate the influence of taurine on the excitability of neuronal networks in the immature neocortex, we performed whole-cell patch-clamp recordings from visually identified pyramidal neurons and interneurons in coronal slices from C57Bl/6 and GAD67-green fluorescent protein (GFP) transgenic mice (postnatal days 2–4). In 46% of the pyramidal neurons bath-application of taurine at concentrations ≥ 300 μM significantly enhanced the frequency of postsynaptic currents (PSCs) by 744.3 ± 93.8% (n = 120 cells). This taurine-induced increase of PSC frequency was abolished by 0.2 μM tetrodotoxin (TTX), 1 μM strychnine or 3 μM gabazine, but was unaffected by the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (±) R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), suggesting that taurine specifically activates GABAergic network activity projecting to pyramidal neurons. Cell-attached recordings revealed that taurine enhanced the frequency of action potentials (APs) in pyramidal neurons, indicating an excitatory action of the GABAergic PSCs. In order to identify the presynaptic targets of taurine we demonstrate that bath application of taurine induced in GAD67-GFP labeled interneurons an inward current that is mainly mediated by glycine receptors and can generate APs in these cells. We conclude from these results that taurine can enhance network excitability in the immature neocortex by selectively activating GABAergic interneurons via interactions with glycine receptors. PMID:24550782

  14. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    PubMed

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  15. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

    PubMed Central

    van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

    2015-01-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  16. Oral methylphenidate alleviates the fine motor dysfunction caused by chronic postnatal manganese exposure in adult rats.

    PubMed

    Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R

    2015-04-01

    Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. PMID:25601986

  17. Oral Methylphenidate Alleviates the Fine Motor Dysfunction Caused by Chronic Postnatal Manganese Exposure in Adult Rats

    PubMed Central

    Strupp, Barbara J.; Lasley, Stephen M.; Fornal, Casimir A.; Mandal, Shyamali; Smith, Donald R.

    2015-01-01

    Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. PMID:25601986

  18. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  19. Fetal-Adult Cardiac Transcriptome Analysis in Rats with Contrasting Left Ventricular Mass Reveals New Candidates for Cardiac Hypertrophy

    PubMed Central

    Grabowski, Katja; Riemenschneider, Mona; Schulte, Leonard; Witten, Anika; Schulz, Angela; Stoll, Monika; Kreutz, Reinhold

    2015-01-01

    Reactivation of fetal gene expression patterns has been implicated in common cardiac diseases in adult life including left ventricular (LV) hypertrophy (LVH) in arterial hypertension. Thus, increased wall stress and neurohumoral activation are discussed to induce the return to expression of fetal genes after birth in LVH. We therefore aimed to identify novel potential candidates for LVH by analyzing fetal-adult cardiac gene expression in a genetic rat model of hypertension, i.e. the stroke-prone spontaneously hypertensive rat (SHRSP). To this end we performed genome-wide transcriptome analysis in SHRSP to identify differences in expression patterns between day 20 of fetal development (E20) and adult animals in week 14 in comparison to a normotensive rat strain with contrasting low LV mass, i.e. Fischer (F344). 15232 probes were detected as expressed in LV tissue obtained from rats at E20 and week 14 (p < 0.05) and subsequently screened for differential expression. We identified 24 genes with SHRSP specific up-regulation and 21 genes with down-regulation as compared to F344. Further bioinformatic analysis presented Efcab6 as a new candidate for LVH that showed only in the hypertensive SHRSP rat differential expression during development (logFC = 2.41, p < 0.001) and was significantly higher expressed in adult SHRSP rats compared with adult F344 (+ 76%) and adult normotensive Wistar-Kyoto rats (+ 82%). Thus, it represents an interesting new target for further functional analyses and the elucidation of mechanisms leading to LVH. Here we report a new approach to identify candidate genes for cardiac hypertrophy by combining the analysis of gene expression differences between strains with a contrasting cardiac phenotype with a comparison of fetal-adult cardiac expression patterns. PMID:25646840

  20. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    SciTech Connect

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  1. AAV9 supports wide-scale transduction of the CNS and TDP-43 disease modeling in adult rats

    PubMed Central

    Jackson, Kasey L; Dayton, Robert D; Klein, Ronald L

    2015-01-01

    AAV9 has emerged as an efficient adeno-associated virus (AAV) serotype for gene transfer to the central nervous system. We have used this technique to study aspects of amyotrophic lateral sclerosis (ALS) by administering AAV encoding the ALS-related gene transactive response DNA binding protein of 43 kDa (TDP-43) to neonatal rats. However, inducing the expression in adult subjects would be preferable to mimic the adult onset of symptoms in ALS. We expressed either green fluorescent protein (GFP) or TDP-43 in adult rats after an intravenous (i.v.) route of administration to attempt wide-scale transduction of the spinal cord for disease modeling. In order to optimize the gene transfer, we made comparisons of efficiency by age, gender, and across several AAV serotypes (AAV1, AAV8, AAV9, and AAV10). The data indicate more efficient neuronal transduction in neonates, with little evidence of glial transduction at either age, no gender-related differences in transduction, and that AAV9 was efficient in adults relative to the other serotypes tested. Based on these data, AAV9 TDP-43 was expressed at three vector doses in adult female rats yielding highly consistent, dose-dependent motor deficits. AAV9 can be delivered i.v. to adult rats to achieve consistent pathophysiological changes and a relevant adult-onset system for disease modeling. PMID:26445725

  2. Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age.

    PubMed

    Teunis, Marc A T; Heijnen, Cobi J; Sluyter, Frans; Bakker, Joost M; Van Dam, Anne-Marie M W; Hof, Maleen; Cools, Alexander R; Kavelaars, Annemieke

    2002-12-01

    Maternal deprivation of neonatal animals has been shown to induce long-lasting changes in the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether maternal deprivation also affects susceptibility to immune-mediated diseases such as experimental autoimmune encephalomyelitis (EAE) in adult life. To this end, 9-day-old rat pups were subjected to a short-lasting maternal deprivation for a period of 24 h. At the age of 8 weeks, we induced EAE in these rats by immunization with myelin basic protein (MBP) in complete Freund's adjuvant. Our data demonstrate that short-lasting maternal deprivation induces a marked increase in the severity of EAE in the animals in later life. The histopathological evaluation of spinal cord and cerebellum corresponded with the observed differences in clinical symptoms of EAE. Moreover, neonatal maternal deprivation affects macrophage functioning at adult age. In contrast, no differences were observed in in vitro mitogen- and MBP-induced cytokine production by splenocytes. LPS-induced corticosterone release did not differ either between maternally deprived and control animals. We conclude that short-lasting neonatal maternal deprivation of rat pups has long-lasting consequences for macrophage activity and for susceptibility to the inflammatory autoimmune disease EAE. PMID:12446005

  3. Differential, regional, and cellular expression of the stathmin family transcripts in the adult rat brain.

    PubMed

    Ozon, S; El Mestikawy, S; Sobel, A

    1999-06-01

    Stathmin is a ubiquitous cytosolic phosphoprotein, preferentially expressed in the nervous system, and previously described as a relay integrating diverse intracellular signaling pathways. Stathmin is the generic element of a mammalian protein family including SCG10, SCLIP, and RB3 with its splice variants RB3' and RB3". In contrast with stathmin, SCG10, SCLIP, and RB3/RB3'/RB3" are exclusively expressed in the nervous system, stathmin and SCG10 being mostly expressed during cell proliferation and differentiation, and SCLIP and RB3 rather in mature neural cells. To further understand their specific roles in the CNS, we compared the localization of the stathmin, SCG10, SCLIP, and RB3 transcripts in adult rat brain. Northern blot analysis as well as in situ hybridization experiments showed that all stathmin-related mRNAs are expressed in a wide range of adult rat brain areas. At a regional level, SCG10 and SCLIP appear generally distributed similarly except in a few areas. The pattern of expression of the RB3 transcript is very different from that of the three other members of the stathmin family. Furthermore, unlike SCG10 and SCLIP, which were detected only in neurons, but like stathmin, RB3 was detected in neurons and also in glial cells of the white matter. Altogether, our results suggest distinct roles for each member of the stathmin-related phosphoprotein family, in regard to their specific regional and cellular localization in the rat brain. PMID:10369222

  4. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats. PMID:27092594

  5. Effects of moderate zinc deficiency on cognitive performance in young adult rats.

    PubMed

    Massaro, T F; Mohs, M; Fosmire, G

    1982-07-01

    Two experiments were conducted to establish a dietary zinc level which approximates a moderate deficiency in the young adult rat and to determine if a concurrent zinc deficiency affects cognitive performance. Male rats were fed varying levels of zinc in diet throughout a 17-day period. The lowest dietary level that depressed serum and bone zinc without influencing food consumption or body weight gains was observed to be 5.8 microgram Zn/g diet. Young adult rats maintained on either a zinc adequate (24.4 microgram Zn/g) or low-zinc (5.3 microgram Zn/g) diet were tested in a modified Skinner Box involving tests of visual, auditory, association, and discrimination learning. No differences were observed in the visual discrimination performance of the zinc deficient animals when compared with control counterparts. Deficits in the ability to transfer a learned association between visual and auditory stimuli were observed, however, in the deficient group during the transfer test phase. The latter performed better during the final auditory discrimination task in transferring a learned food-relevant cue. PMID:7122717

  6. Complete Thymectomy in Adult Rats with Non-invasive Endotracheal Intubation

    PubMed Central

    Rendell, Victoria R.; Giamberardino, Charles; Li, Jie; Markert, M. Louise; Brennan, Todd V.

    2015-01-01

    Thymectomy in neonatal rodents is an established and reliable procedure for immunological studies. However, in adult rats, complications of hemorrhage and pneumothorax from pleural disruption can result in a significant mortality rate. This protocol is a simple method of rat thymectomy that utilizes a mini-sternotomy and endotracheal intubation. Intubation is accomplished with a non-invasive and easily reproducible method and allows for positive pressure ventilation to prevent pneumothorax and a controlled airway that allows sufficient time for careful thymus dissection to minimize pleural disruption. A 1.5 cm sternal incision decreases contact with mediastinal vessels and pleura, while still providing full visualization of the thymus. Following exposure of the mediastinum, the thymus is removed by blunt dissection under magnification. The pleural space is then sealed by suture closure of the pre-tracheal muscles followed by the application of surgical glue. The thorax is then closed by suture closure of the sternum, followed by suture closure of the skin. All thymectomies were complete as evidenced by immunohistochemical (IHC) staining of mediastinal tissue, and absence of naïve T-cells by flow cytometry, and the procedure had a 96% survival rate. This method is suitable when complete thymectomy with minimal complications is desired for further immunological studies in athymic adult rats. PMID:25590868

  7. Effect of long-term ingestion of chromium compounds on aggression, sex behavior and fertility in adult male rat.

    PubMed

    Bataineh, H; al-Hamood, M H; Elbetieha, A; Bani Hani, I

    1997-08-01

    The effects of long-term ingestion of chromium chloride (trivalent compound) and potassium dichromate (hexavalent compound) was investigated on sexual behavior, aggressive behavior and fertility in male rats. Adult male rats were exposed to chromium chloride and potassium dichromate in drinking water at a concentration of 1000 ppm for 12 weeks. The exposure of male rats to chromium chloride and potassium dichromate reduced the number of mounts. The exposure of male rats to potassium dichromate increased the time to ejaculation. On the other hand, the exposure of male rats to chromium chloride and potassium dichromate increased the post ejaculatory interval. The number of animals ejaculating were reduced in chromium chloride and potassium dichromate exposed male rats. The exposure of male rats to chromium chloride and potassium dichromate decreased lateralizations, boxing bouts and fights with stud male. The exposure of male rats to chromium chloride and potassium dichromate had no effect on fertility. Testes, seminal vesicle and preputial gland weights were significantly reduced in chromium chloride- and potassium dichromate-exposed males. In conclusion, the long-term ingestion of chromium chloride and potassium dichromate would have adverse effects on sexual behavior and territorial aggression in adult male rat. PMID:9292274

  8. Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system.

    PubMed

    Flood, D G; Finn, J P; Walton, K M; Dionne, C A; Contreras, P C; Miller, M S; Bhat, R V

    1998-08-31

    Cell survival, death, and stress signals are transduced from the cell surface to the cytoplasm and nucleus via a cascade of phosphorylation events involving the mitogen-activated protein kinase (MAPK) family. We compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of stress and death signals) in the adult rat central nervous system. All four kinases were present in the cytoplasm, dendrites, and axons of neurons. The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. A high degree of correspondence was found between the regional distribution of MEK1 and p42MAPK. Immunostaining for MEK1 and p42MAPK was intense in olfactory structures, neocortex, hippocampus, striatum, midline, and interlaminar thalamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord. In addition to neurons, p42MAPK was also present in oligodendrocytes. Whereas MEK4 was ubiquitously distributed, JNK1 was more selective. Immunostaining for MEK4 and JNK1 was intense in the olfactory bulb, lower cortical layers, the cholinergic basal forebrain, most nuclei of the thalamus, medial habenula, and cranial motor nuclei. The distribution of MEK1 and p42MAPK proteins only partially overlapped with that of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily act to counterbalance each other in response to extracellular stimuli. The differential distribution of these kinases may control the specificity of neuronal function to extracellular signals. PMID:9714150

  9. Does prenatal methamphetamine exposure induce cross-sensitization to cocaine and morphine in adult male rats?

    PubMed

    Slamberová, R; Yamamotová, A; Pometlová, M; Schutová, B; Hrubá, L; Nohejlová-Deykun, K; Nová, E; Macúchová, E

    2012-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected. PMID:22980560

  10. Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

    PubMed

    Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

    2013-09-01

    Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. PMID:23447367

  11. Integrated phrenic responses to carotid afferent stimulation in adult rats following perinatal hyperoxia.

    PubMed Central

    Ling, L; Olson, E B; Vidruk, E H; Mitchell, G S

    1997-01-01

    1. Hypoxic ventilatory responses are greatly attenuated in adult rats exposed to moderate hyperoxia (60% O2) during the first month of life (perinatal treated rats). The present study was designed to test the hypothesis that perinatal hyperoxia impairs central integration of carotid chemoreceptor afferent inputs, thereby diminishing the hypoxic ventilatory response. 2. Time-dependent phrenic nerve responses to electrical stimulation of the carotid sinus nerve (CSN) and steady-state relationships between CSN stimulation frequency and phrenic nerve output were compared in control and perinatal treated rats. The rats were urethane anaesthetized, vagotomized, paralysed and artificially ventilated. End-tidal CO2 was monitored and maintained at isocapnic levels; arterial blood gases were determined. 3. Two stimulation protocols were used: (1) three 2 min episodes of CSN stimulation (20 Hz, 0.2 ms duration, 3 x threshold), separated by 5 min intervals; and (2) nine 45 s episodes of CSN stimulation with stimulus frequencies ranging from 0.5 to 20 Hz (0.2 ms duration, 3 x threshold), separated by 4 min intervals. 4. The mean threshold currents to elicit phrenic responses were similar between groups. Burst frequency (f, burst min-1), peak amplitude of integrated phrenic activity (integral of Phr), and minute phrenic activity (integral of Phr x f) during and after CSN stimulation were not distinguishable between groups in either protocol at any time or at any stimulus intensity (P > 0.05). 5. Perinatal hyperoxia does not alter temporal or steady-state phrenic responses to CSN stimulation, suggesting that the central integration of carotid chemoreceptor afferent inputs is not impaired in perinatal treated rats. It is speculated that carotid chemoreceptors per se are impaired in perinatal treated rats. PMID:9161991

  12. Postnatal manganese exposure does not alter dopamine autoreceptor sensitivity in adult and adolescent male rats.

    PubMed

    McDougall, Sanders A; Mohd-Yusof, Alena; Kaplan, Graham J; Abdulla, Zuhair I; Lee, Ryan J; Crawford, Cynthia A

    2013-04-15

    Administering manganese chloride (Mn) to rats on postnatal day (PD) 1-21 causes long-term reductions in dopamine transporter levels in the dorsal striatum, as well as a persistent increase in D1 and D2 receptor concentrations. Whether dopamine autoreceptors change in number or sensitivity is uncertain, although D2S receptors, which may be presynaptic in origin, are elevated in Mn-exposed rats. The purpose of this study was to determine if early Mn exposure causes long-term changes in dopamine autoreceptor sensitivity that persist into adolescence and adulthood. To this end, male rats were exposed to Mn on PD 1-21 and autoreceptor functioning was tested 7 or 70 days later by measuring (a) dopamine synthesis (i.e., DOPA accumulation) in the dorsal striatum after quinpirole or haloperidol treatment and (b) behavioral responsiveness after low-dose apomorphine treatment. Results showed that low doses (i.e., "autoreceptor" doses) of apomorphine (0.06 and 0.12 mg/kg) decreased the locomotor activity of adolescent and adult rats, while higher doses increased locomotion. The dopamine synthesis experiment also produced classic autoreceptor effects, because quinpirole decreased dorsal striatal DOPA accumulation; whereas, haloperidol increased DOPA levels in control rats, but not in rats given the nerve impulse inhibitor γ-butyrolactone. Importantly, early Mn exposure did not alter autoreceptor sensitivity when assessed in early adolescence or adulthood. The lack of Mn-induced effects was evident in both the dopamine synthesis and behavioral experiments. When considered together with past studies, it is clear that early Mn exposure alters the functioning of various dopaminergic presynaptic mechanisms, while dopamine autoreceptors remain unimpaired. PMID:23458069

  13. Postnatal manganese exposure does not alter dopamine autoreceptor sensitivity in adult and adolescent male rats

    PubMed Central

    McDougall, Sanders A.; Mohd-Yusof, Alena; Kaplan, Graham J.; Abdulla, Zuhair I.; Lee, Ryan J.; Crawford, Cynthia A.

    2013-01-01

    Administering manganese chloride (Mn) to rats on postnatal day (PD) 1–21 causes long-term reductions in dopamine transporter levels in the dorsal striatum, as well as persistent increases in D1 and D2 receptor concentrations. Whether dopamine autoreceptors change in number or sensitivity is uncertain, although D2S receptors, which may be presynaptic in origin, are elevated in Mn-exposed rats. The purpose of this study was to determine if early Mn exposure causes long-term changes in dopamine autoreceptor sensitivity that persist into adolescence and adulthood. To this end, male rats were exposed to Mn on PD 1–21 and autoreceptor functioning was tested 7 or 70 days later by measuring (a) dopamine synthesis (i.e., DOPA accumulation) in the dorsal striatum after quinpirole or haloperidol treatment and (b) behavioral responsiveness after low-dose apomorphine treatment. Results showed that low doses (i.e., “autoreceptor” doses) of apomorphine (0.06 and 0.12 mg/kg) decreased the locomotor activity of adolescent and adult rats, while higher doses increased locomotion. The dopamine synthesis experiment also produced classic autoreceptor effects, because quinpirole decreased dorsal striatal DOPA accumulation; whereas, haloperidol increased DOPA levels in control rats, but not in rats given the nerve impulse inhibitor γ-butyrolactone. Importantly, early Mn exposure did not alter autoreceptor sensitivity when assessed in early adolescence or adulthood. The lack of Mn-induced effects was evident in both the dopamine synthesis and behavioral experiments. When considered together with past studies, it is clear that early Mn exposure alters the functioning of various dopaminergic presynaptic mechanisms, while dopamine autoreceptors remain unimpaired. PMID:23458069

  14. Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats.

    PubMed

    Schneider, Miriam; Koch, Michael

    2003-10-01

    There is evidence from studies in humans and animals that a vulnerable period for chronic cannabinoid administration exists during certain phases of development. The present study tested the hypothesis that long-lasting interference of cannabinoids with the developing endogenous cannabinoid system during puberty causes persistent behavioral alterations in adult rats. Chronic treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN) (1.2 mg/kg) or vehicle was extended over 25 days either throughout the rats' puberty or for a similar time period in adult rats. The rats received 20 injections intraperitoneally (i.p.), which were not delivered regularly. Adult rats were tested for object recognition memory, performance in a progressive ratio (PR) operant behavior task, locomotor activity, and prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI was significantly disrupted only by chronic peripubertal cannabinoid treatment. This long-lasting PPI deficit was reversed by the acute administration of the dopamine antagonist haloperidol. Furthermore, we found deficits in recognition memory of pubertal-treated rats and these animals showed lower break points in a PR schedule, whereas food preference and locomotion were not affected. Adult chronic cannabinoid treatment had no effect on the behaviors tested. Therefore, we conclude that puberty in rats is a vulnerable period with respect to the adverse effects of cannabinoid treatment. Since PPI deficits, object recognition memory impairments, and anhedonia/avolition are among the endophenotypes of schizophrenia, we propose chronic cannabinoid administration during pubertal development as an animal model for some aspects of the etiology of schizophrenia. PMID:12888772

  15. GABAergic transmission and enhanced modulation by opioids and endocannabinoids in adult rat rostral ventromedial medulla

    PubMed Central

    Li, Ming-Hua; Suchland, Katherine L; Ingram, Susan L

    2015-01-01

    Neurons in the rostral ventromedial medulla (RVM) play critical and complex roles in pain modulation. Recent studies have shown that electrical stimulation of the RVM produces pain facilitation in young animals (postnatal (PN) day < 21) but predominantly inhibits pain behaviours in adults. The cellular mechanisms underlying these changes in RVM modulation of pain behaviours are not known. This is in part because whole-cell patch-clamp studies in RVM to date have been in young (PN day < 18) animals because the organization and abundance of myelinated fibres in this region make the RVM a challenging area for whole-cell patch-clamp recording in adults. Several neurotransmitter systems, including GABAergic neurotransmission, undergo developmental changes that mature by PN day 21. Thus, we focused on optimizing whole-cell patch-clamp recordings for RVM neurons in animals older than PN day 30 and compared the results to animals at PN day 10–21. Our results demonstrate that the probability of GABA release is lower and that opioid and endocannabinoid effects are more evident in adult rats (mature) compared to early postnatal (immature) rats. Differences in these properties of RVM neurons may contribute to the developmental changes in descending control of pain from the RVM to the spinal cord. PMID:25556797

  16. Repeated restraint stress alters sensitivity to the social consequences of ethanol in adolescent and adult rats

    PubMed Central

    Varlinskaya, Elena I.; Doremus-Fitzwater, Tamara L.; Spear, Linda P.

    2010-01-01

    Human adolescents consume alcohol largely to enhance social interactions. Adolescent, but not adult rats likewise exhibit ethanol-induced social facilitation under low-stress circumstances. Since the relationship between stress and ethanol sensitivity across ontogeny still has yet to be well explored, the present study sought to characterize possible age-associated differences in the influence of stressor exposure on ethanol-induced changes in social behavior in adolescent [postnatal days (P) 30–36] and adult (P65-71) male and female Sprague-Dawley rats. Animals were repeatedly restrained (90 min/day) for 5 days, followed by examination of ethanol-induced (0, 0.25, 0.5, 0.75, or 1.0 g/kg) alterations in social behaviors on the last day. Results revealed typical age-related differences in sensitivity to ethanol among controls, with adolescents being uniquely sensitive to low-dose ethanol stimulation of social investigation and play fighting, but less sensitive than adults to the social suppression emerging at higher doses. At both ages, stressor exposure decreased sensitivity to social inhibitory effects of ethanol, while augmenting expression of ethanol’s social facilitatory effects. Ethanol also attenuated the stress-related suppression of social motivation at both ages. These results suggest that repeated stressor exposure diminishes age-related differences in the social consequences of ethanol, with stress enhancing ethanol-induced social facilitation across age. PMID:20478326

  17. The longitudinal study of rat hippocampus influenced by stress: early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats.

    PubMed

    Jin, Fengkui; Li, Lei; Shi, Mei; Li, Zhenzi; Zhou, Jinghua; Chen, Li

    2013-06-01

    Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats' spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus. PMID:23500055

  18. Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

    PubMed

    Mabrouk, Aymen; Ben Cheikh, Hassen

    2016-06-01

    This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication. PMID:25216800

  19. A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats.

    PubMed

    Lin, Tiao; Tong, Wei; Chandra, Abhishek; Hsu, Shao-Yun; Jia, Haoruo; Zhu, Ji; Tseng, Wei-Ju; Levine, Michael A; Zhang, Yejia; Yan, Shi-Gui; Liu, X Sherry; Sun, Dongming; Young, Wise; Qin, Ling

    2015-01-01

    Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI. PMID:26528401

  20. Bisphenol A does not affect memory performance in adult male rats.

    PubMed

    Kuwahara, Rika; Kawaguchi, Shinichiro; Kohara, Yumi; Jojima, Takeshi; Yamashita, Kimihiro

    2014-04-01

    Bisphenol A (BPA) is an estrogenic endocrine disruptor used for producing polycarbonate plastics and epoxy resins. This study investigated the effects of oral BPA administration on memory performance, general activity, and emotionality in adult male Sprague Dawley rats using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) used to assess spatial memory performance. In addition, in order to confirm the effects of BPA on spatial memory performance, we examined whether intrahippocampal injection of BPA affects spatial memory consolidation. In the MAZE test, although oral BPA administration at 10 mg/kg significantly altered the number of entries into the incorrect area compared to those of vehicle-treated rats, male rats given BPA through either oral administration or intrahippocampal injection failed to show significant differences in latencies to reach the reward. Also, oral BPA administration did not affect fear-motivated memory performance in the step-through passive avoidance test. Oral BPA administration at 0.05 mg/kg, the lowest dose used in this study, was correlated with a decrease in locomotor activity in the open-field test, whereas oral administration at 10 mg/kg, the highest dose used in this study, was correlated with a light anxiolytic effect in the elevated plus-maze test. The present study suggests that BPA in adulthood has little effect on spatial memory performance in male rats. PMID:24326521

  1. Lifespan Changes in the Countermanding Performance of Young and Middle Aged Adult Rats.

    PubMed

    Beuk, Jonathan; Beninger, Richard J; Paré, Martin

    2016-01-01

    Inhibitory control can be investigated with the countermanding task, which requires subjects to make a response to a go signal and cancel that response when a stop signal is presented occasionally. Adult humans performing the countermanding task typically exhibit impaired response time (RT), stop signal response time (SSRT) and response accuracy as they get older, but little change in post-error slowing. Rodent models of the countermanding paradigm have been developed recently, yet none have directly examined age-related changes in performance throughout the lifespan. Male Wistar rats (N = 16) were trained to respond to a visual stimulus (go signal) by pressing a lever directly below an illuminated light for food reward, but to countermand the lever press subsequent to a tone (stop signal) that was presented occasionally (25% of trials) at a variable delay. Subjects were tested in 1 h sessions at approximately 7 and 12 months of age with intermittent training in between. Rats demonstrated longer go trial RT, a higher proportion of go trial errors and performed less total trials at 12, compared to 7 months of age. Consistent SSRT and post-error slowing were observed for rats at both ages. These results suggest that the countermanding performance of rats does vary throughout the lifespan, in a manner similar to humans, suggesting that rodents may provide a suitable model for behavioral impairment related to normal aging. These findings also highlight the importance of indicating the age at which rodents are tested in countermanding investigations. PMID:27555818

  2. Tactile stimulation promotes motor recovery following cortical injury in adult rats.

    PubMed

    Gibb, Robbin L; Gonzalez, Claudia L R; Wegenast, Will; Kolb, Bryan E

    2010-12-01

    Tactile stimulation has been reported to be effective as a treatment for inducing growth in premature human babies and infant rats and for improving functional recovery after brain injury in infant rats. We wondered if the behavioral impairments following injury in adulthood would show similar improvements with tactile stimulation. To test this hypothesis, rats were given either bilateral medial frontal cortex aspiration lesions or a unilateral focal stroke produced in the sensorimotor cortex using the pial stripping technique. In both conditions, rats that were designated to the tactile stimulation treatment group received the stimulation for one week before the surgery to accustom them to the stimulation procedure and then two weeks postoperatively. After a three-week recovery period, the animals with frontal damage were tested in a tray-reaching task. Animals with sensorimotor cortex damage were tested in a single pellet reaching task. Following behavioral testing brains were processed for Golgi-Cox analyses. Marked improvement was found in motor performance in the lesion-tactile stimulation animals regardless of the nature of the cortical injury. The observed behavioral recovery was associated with an increase in dendritic length in pyramidal cells adjacent cortex in the frontal operates and in the intact sensorimotor cortex in the stroke animals. Taken together, these data show tactile stimulation can improve motor performance in adult animals and the improvement is correlated with dendritic sprouting. This finding could have implications for therapy in humans following stroke. PMID:20394780

  3. Lifespan Changes in the Countermanding Performance of Young and Middle Aged Adult Rats

    PubMed Central

    Beuk, Jonathan; Beninger, Richard J.; Paré, Martin

    2016-01-01

    Inhibitory control can be investigated with the countermanding task, which requires subjects to make a response to a go signal and cancel that response when a stop signal is presented occasionally. Adult humans performing the countermanding task typically exhibit impaired response time (RT), stop signal response time (SSRT) and response accuracy as they get older, but little change in post-error slowing. Rodent models of the countermanding paradigm have been developed recently, yet none have directly examined age-related changes in performance throughout the lifespan. Male Wistar rats (N = 16) were trained to respond to a visual stimulus (go signal) by pressing a lever directly below an illuminated light for food reward, but to countermand the lever press subsequent to a tone (stop signal) that was presented occasionally (25% of trials) at a variable delay. Subjects were tested in 1 h sessions at approximately 7 and 12 months of age with intermittent training in between. Rats demonstrated longer go trial RT, a higher proportion of go trial errors and performed less total trials at 12, compared to 7 months of age. Consistent SSRT and post-error slowing were observed for rats at both ages. These results suggest that the countermanding performance of rats does vary throughout the lifespan, in a manner similar to humans, suggesting that rodents may provide a suitable model for behavioral impairment related to normal aging. These findings also highlight the importance of indicating the age at which rodents are tested in countermanding investigations. PMID:27555818

  4. A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

    PubMed Central

    Lin, Tiao; Tong, Wei; Chandra, Abhishek; Hsu, Shao-Yun; Jia, Haoruo; Zhu, Ji; Tseng, Wei-Ju; Levine, Michael A; Zhang, Yejia; Yan, Shi-Gui; Liu, X Sherry; Sun, Dongming; Young, Wise; Qin, Ling

    2015-01-01

    Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI. PMID:26528401

  5. Sodium metabisulfite-induced changes on testes, spermatogenesis and epididymal morphometric values in adult rats

    PubMed Central

    Shekarforoush, Shahnaz; Ebrahimi, Zahra; Hoseini, Maryam

    2015-01-01

    Background: Sulphites are widely used as a preservative and antioxidant additives in the food and pharmaceutical industries. Many types of biological and toxicological effects of sulphites in multiple organs of mammals have been shown in previous studies. Objective: The aim of this study was to investigate the effects of sodium metabisulfite (SMB) on testicular function and morphometric values of epididymis in adult male Wistar rats. Materials and Methods: A total of 32 rats were randomly divided into four groups. The experimental groups received SMB at doses of 10 mg/kg (S10), 100mg/kg (S100), and 260 mg/kg (S260) while an equal volume of normal saline was administered to the control group via gavage. The rats were anaesthetized after 28 days and the left testis with the head of epididimis was excised following abdominal incision for histological observation using hematoxylin and eosin staining. Serum samples were collected for assay of testosterone level. The initial epididymis was analyzed for motility, morphology, and the number of sperms. Result: The results of this study showed that normal morphology, count, and motility of sperms and testosterone level were decreased in the SMB treated groups. In comparison with the control group, SMB resulted in a lower total number of spermatogonia, primary spermatocyte, spermatids, and Leydig cells. Conclusion: It is suggested that SMB decreases the sperm production and has the potential to affect the fertility adversely in male rats. PMID:27141536

  6. Functional evidence of α1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

    PubMed Central

    Villalobos-Molina, Rafael; López-Guerrero, J Javier; Ibarra, Maximiliano

    1999-01-01

    The role of α1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective α1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of α1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure. PMID:10323583

  7. Functional evidence of alpha1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats.

    PubMed

    Villalobos-Molina, R; López-Guerrero, J J; Ibarra, M

    1999-04-01

    The role of alpha1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of alpha1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure. PMID:10323583

  8. Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

    PubMed Central

    Hamilton, Derek A.; Magcalas, Christy M.; Barto, Daniel; Bird, Clark W.; Rodriguez, Carlos I.; Fink, Brandi C.; Pellis, Sergio M.; Davies, Suzy; Savage, Daniel D.

    2014-01-01

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE1, and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring. PMID:25549080

  9. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-01-01

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring. PMID:25549080

  10. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs. PMID:24768639

  11. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  12. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

    PubMed Central

    Saunders, Norman R.; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Habgood, Mark D.; Wakefield, Matthew J.; Lindsay, Helen; Stratzielle, Nathalie; Ghersi-Egea, Jean-Francois; Liddelow, Shane A.

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2–98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients. PMID:25972776

  13. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study.

    PubMed

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D; Wakefield, Matthew J; Lindsay, Helen; Stratzielle, Nathalie; Ghersi-Egea, Jean-Francois; Liddelow, Shane A

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2-98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients. PMID:25972776

  14. Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry

    PubMed Central

    Hiraoka, Kotaro; Sumiyoshi, Akira; Nonaka, Hiroi; Kikkawa, Takako; Kawashima, Ryuta; Osumi, Noriko

    2016-01-01

    Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors. PMID:27355350

  15. Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry.

    PubMed

    Hiraoka, Kotaro; Sumiyoshi, Akira; Nonaka, Hiroi; Kikkawa, Takako; Kawashima, Ryuta; Osumi, Noriko

    2016-01-01

    Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors. PMID:27355350

  16. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

    PubMed

    Yucel, Atakan; Yucel, Nermin; Ozkanlar, Seckin; Polat, Elif; Kara, Adem; Ozcan, Halil; Gulec, Mustafa

    2016-04-01

    Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further. PMID:26970810

  17. Repeated Ketamine Exposure Induces an Enduring Resilient Phenotype in Adolescent and Adult Rats

    PubMed Central

    Parise, Eric M.; Alcantara, Lyonna F.; Warren, Brandon L.; Wright, Katherine N.; Hadad, Roey; Sial, Omar K.; Kroeck, Kyle G.; Iñiguez, Sergio D.; Bolaños-Guzmán, Carlos A.

    2013-01-01

    Background Major Depressive Disorder (MDD) afflicts up to 10% of adolescents. However, nearly 50% of those afflicted are considered non-responsive to available treatments. Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist has shown potential as a rapid-acting and long-lasting treatment for MDD in adults. Thus, the effectiveness and functional consequences of ketamine exposure during adolescence were explored. Methods Adolescent male rats (postnatal day [PD] 35) received two ketamine (0, 5, 10 or 20 mg/kg) injections, 4 hours apart, after exposure to day 1 of the forced swim test (FST). The next day, rats were re-exposed to the FST to assess ketamine-induced antidepressant-like responses. Separate groups were exposed to chronic unpredictable stress (CUS) to confirm findings from the FST. After these initial experiments, adolescent naïve rats were exposed to either 1 or 15 consecutive days (PD35–49) of ketamine (20 mg/kg) twice/daily. Ketamine's influence on behavioral reactivity to rewarding (i.e., sucrose preference) and aversive (i.e., elevated plus-maze, FST) circumstances was then assessed 2 months after treatment. To control for age-dependent effects, adult rats (PD75–89) were exposed to identical experimental conditions. Results Ketamine (20 mg/kg) reversed the CUS-induced depression-like behaviors in the FST. Repeated ketamine exposure resulted in anxiolytic- and antidepressant-like responses 2 months after drug exposure. None of the ketamine doses used were capable of inducing drug-seeking behaviors as measured by place preference conditioning. Conclusions Repeated ketamine exposure induces enduring resilient-like responses regardless of age of exposure. These findings point to ketamine, and its repeated exposure, as a potentially useful antidepressant during adolescence. PMID:23790225

  18. Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, S. A.; Allen, M. R.; Hogan, H. A.; Delp, M. D.

    2002-01-01

    The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

  19. Comparative analysis of antioxidants against cadmium induced reproductive toxicity in adult male rats.

    PubMed

    Jahan, Sarwat; Khan, Mehreen; Ahmed, Shakeel; Ullah, Hizb

    2014-02-01

    The present study was conducted to compare and evaluate the potential benefits of three different antioxidants in reversing cadmium (Cd)-induced reproductive toxicity in adult male rats. Rats (n = 5) weighing 180 +/- 20 gm were divided into five groups (control, Cd, Cd + sulforaphane, Cd + vitamin E, and Cd + plant extract). Treated groups received CdCl2 (0.2 mg/kg), sulforaphane (25 µg/rat), vitamin E (75 mg/kg), and plant extract (100 mg/kg) for 15 days. Blood samples and testicular tissues were obtained for estimation of testosterone, Zn, and Cd concentration and daily sperm production/efficiency of sperm production. Cadmium exposure caused a significant decrease in final body weight (p < 0.0001). The plasma concentrations of Cd were significantly increased and Zn concentration decreased (p < 0.0001) in the Cd group as compared to the control group. The testicular concentrations of Cd were significantly increased and Zn concentration decreased (p < 0.0001) in the Cd group as compared to the control group. Cadmium exposure caused a significant decrease (p < 0.0001) in plasma testosterone concentrations and daily sperm production as compared to the control group. More significant effects were observed with Cd+sulforaphane, Cd + vitamin E, and Cd + plant extract treated groups in slashing Cd-induced toxicity. Present findings suggest that Ficus religiosa and sulforaphane are more powerful antioxidants as compared to vitamin E in reversing the oxidative stress and can have a protective role against Cd induced reproductive toxicity in adult male rats. Part of the mechanism involved in this protective role seems to be associated with the antioxidant properties of these agents in reducing reproductive damage. PMID:24156729

  20. AMNESIA FOR EARLY LIFE STRESS DOES NOT PRECLUDE THE ADULT DEVELOPMENT OF PTSD SYMPTOMS IN RATS

    PubMed Central

    Poulos, Andrew M.; Reger, Maxine; Mehta, Nehali; Zhuravka, Irina; Sterlace, Sarah S.; Gannam, Camille; Hovda, David A.; Giza, Christopher C.; Fanselow, Michael

    2013-01-01

    Background Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development are a significant risk factor for later life anxiety disorders such as post-traumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD such as enhanced fear and anxiety. Here we used a fear conditioning procedure in juvenile rats prior to maturation of the neural systems supporting declarative memory to assess the necessity of early memory to the later life development of PTSD related symptoms. Methods Nineteen-day old rats were exposed to unpredictable and inescapable footshocks and fear memory for the shock context was assessed during adulthood. Thereafter, adult animals were either exposed to single-trial fear conditioning, elevated plus-maze or sacrificed for basal diurnal corticosterone and quantification of neuronal glucocorticoid (G-R) and Neuropeptide Y receptors. Results Early trauma exposed rats displayed stereotypic footshock reactivity, yet by adulthood, hippocampus-dependent contextual fear related memory was absent. However, adult rats showed sensitized fear learning, aberrant basal circadian fluctuations of corticosterone, increased amygdalar G-R, decreased time spent in the open arm of an elevated plus maze and an odor aversion associated with early-life footshocks. Conclusions These results suggest that traumatic experience during developmental periods of hippocampal immaturity can promote lifelong changes in symptoms and neuropathology associated with human PTSD even if there is no explicit memory of the early trauma. PMID:24231200

  1. Gender and estrous cycle influences on behavioral and neurochemical alterations in adult rats neonatally administered ketamine.

    PubMed

    Célia Moreira Borella, Vládia; Seeman, Mary V; Carneiro Cordeiro, Rafaela; Vieira dos Santos, Júnia; Romário Matos de Souza, Marcos; Nunes de Sousa Fernandes, Ethel; Santos Monte, Aline; Maria Mendes Vasconcelos, Silvânia; Quinn, John P; de Lucena, David F; Carvalho, André F; Macêdo, Danielle

    2016-05-01

    Neonatal N-methyl-D-aspartate (NMDA) receptor blockade in rodents triggers schizophrenia (SCZ)-like alterations during adult life. SCZ is influenced by gender in age of onset, premorbid functioning, and course. Estrogen, the hormone potentially driving the gender differences in SCZ, is known to present neuroprotective effects such as regulate oxidative pathways and the expression of brain-derived neurotrophic factor (BDNF). Thus, the aim of this study was to verify if differences in gender and/or estrous cycle phase during adulthood would influence the development of behavioral and neurochemical alterations in animals neonatally administered ketamine. The results showed that ketamine-treated male (KT-male) and female-in-diestrus (KTF-diestrus, the low estrogen phase) presented significant deficits in prepulse inhibition of the startle reflex and spatial working memory, two behavioral SCZ endophenotypes. On the contrary, female ketamine-treated rats during proestrus (KTF-proestrus, the high estradiol phase) had no behavioral alterations. This correlated with an oxidative imbalance in the hippocampus (HC) of both male and KTF-diestrus female rats, that is, decreased levels of GSH and increased levels of lipid peroxidation and nitrite. Similarly, BDNF was decreased in the KTF-diestrus rats while no alterations were observed in KTF-proestrus and male animals. The changes in the HC were in contrast to those in the prefrontal cortex in which only increased levels of nitrite in all groups studied were observed. Thus, there is a gender difference in the adult rat HC in response to ketamine neonatal administration, which is based on the estrous cycle. This is discussed in relation to neuropsychiatric conditions and in particular SCZ. PMID:26215537

  2. Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring

    PubMed Central

    Lacy, Ryan T.; Hord, Lauren L.; Morgan, Amanda J.; Harrod, Steven B.

    2012-01-01

    Background Prenatal tobacco smoke exposure is associated with alterations in motivated behavior in offspring, such as increased consumption of highly palatable foods and abused drugs. Animal models show that gestational nicotine (GN) exposure mediates changes in responding for sucrose and drug reward. Methods A novel, intermittent low-dose intravenous (IV) exposure model was used to administer nicotine (0.05 mg/kg/injection) or saline 3×/day to rats on gestational days 8-21. Two experiments investigated the effect of IV GN on 1) the habituation of spontaneous locomotor activity and on 2) sucrose reinforced responding in offspring. For the operant experiments, animals acquired fixed-ratio (FR-3) responding for sucrose, 26% (w/v), and were tested on varying concentrations (0, 3, 10, 30, 56%; Latin-square) according to a FR-3, and then a progressive-ratio (PR) schedule. Male and female adult offspring were used. Results IV GN did not alter birth or growth weight, or the number of pups born. No between-group differences in habituation to spontaneous locomotor activity were observed. FR testing produced an inverted U-shaped response curve, and rats showed peak responding for 10% sucrose reinforcement. Neither gestation nor sex affected responding, suggesting equivalent sensitivity to varying sucrose concentrations. PR testing revealed that GN rats showed greater motivation for sucrose reinforcement relative to controls. Conclusions A low-dose, IV GN exposure model resulted in increased motivation to respond for sucrose reinforcement in adult offspring. This suggests that using a low number of cigarettes throughout pregnancy will result in increased motivation for highly palatable foods in adult, and perhaps, adolescent offspring. PMID:22377090

  3. Increased excitability and molecular changes in adult rats after a febrile seizure.

    PubMed

    Reid, Aylin Y; Riazi, Kiarash; Campbell Teskey, G; Pittman, Quentin J

    2013-04-01

    Both early life inflammation and prolonged febrile seizures have been associated with increased excitation in the adult brain. We hypothesized this may be due in part to changes in the cation-chloride cotransporter system. Rat pups received saline or lipopolysaccharide/kainic acid (LPS/KA) resulting in inflammation, followed by a behavioral febrile seizure (FS) in approximately 50% of rats. Adult animals from the saline, inflammation, or inflammation + FS groups underwent the following: (1) in vitro electrophysiologic studies; (2) Western blotting or polymerase chain reaction; or (3) application of the Na-K-Cl cotransporter 1 (NKCC1) blocker bumetanide to determine its effect on reversing increased excitability in vitro. The inflammation and inflammation + FS groups demonstrated increased excitability in vitro and increased hippocampal protein expression of NR2B and GABAA α5 receptor subunits and mRNA expression of NKCC1. The inflammation + FS group also had decreased protein expression of GluR2 and GABAA α1 receptor subunits and mRNA and protein expression of KCC2. Bumetanide decreased in vitro 4-aminopyridine-induced inter-ictal activity in the inflammation and inflammation + FS groups. The results demonstrate early-life inflammation with or without a behavioral FS can lead to long-lasting molecular changes and increased excitability in the adult rat hippocampus, although some changes are more extensive when inflammation is accompanied by behavioral seizure activity. Bumetanide is effective in reversing increased excitability in vitro, providing evidence for a causal role for cation-chloride cotransporters and suggesting this drug may prove useful for treating epilepsy that develops after a FS. PMID:23293960

  4. Thermoregulatory deficits in adult Long Evans rat exposed perinatally to the antithyroidal drug, propylthiouracil.

    PubMed

    Johnstone, Andrew F M; Gilbert, Mary E; Aydin, Cenk; Grace, Curtis E; Hasegawa, Masashi; Gordon, Christopher J

    2013-01-01

    Developmental exposure to endocrine disrupting drugs and environmental toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (T(c)) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic pituitary thyroid (HPT) axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor. Propylythiouracil (PTU) was used as a prototypical compound because of its well known antithyroidal properties. PTU was added to the drinking water of pregnant rats in concentrations of 0, 1, 2, 3, and 10 ppm from gestational day (GD) 6 through postnatal day (PND) 21. Adult male offspring were implanted with radiotransmitters to monitor Tc and motor activity (MA) and were observed undisturbed at an ambient temperature of 22 °C for 12 consecutive days. Data were averaged into a single 24 hour period to minimize impact of ultradian changes in T(c) and MA. All treatment groups showed a distinct circadian temperature rhythm. Rats exposed to 10 ppm PTU exhibited a marked deviation in their regulated T(c) with a reduction of approximately 0.4 °C below that of controls throughout the daytime period and a smaller reduction at night. Rats exposed to 1 or 2 ppm also had smaller but significant reductions in T(c). MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an antithyroidal drug led to an apparent permanent reduction in T(c) of adult offspring that was independent of changes in MA. PMID:23732561

  5. Adolescent, but not adult, rats exhibit ethanol-mediated appetitive second-order conditioning

    PubMed Central

    Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia; Molina, Juan Carlos; Spear, Norman E.

    2008-01-01

    Background Adolescent rats are less sensitive to the sedative effects of ethanol than older animals. They also seem to perceive the reinforcing properties of ethanol. However, unlike neonates or infants, ethanol-mediated appetitive behavior has yet to be clearly shown in adolescents. Appetitive ethanol reinforcement was assessed in adolescent (postnatal day 33, P33) and adult rats (P71) through second-order conditioning (SOC). Methods On P32 or P70 animals were intragastrically administered ethanol (0.5 or 2.0 g/kg) paired with intraoral pulses of sucrose (CS1, first-order conditioning phase). CS1 delivery took place either 5-20 (Early pairing) or 30-45 (Late pairing) min following ethanol. CS1 exposure and ethanol administration were separated by 240 min in unpaired controls. On P33 or P71, animals were presented the CS1 (second-order conditioning phase) while in a distinctive chamber (CS2). Then, they were tested for CS2 preference. Results Early and late paired adolescents, but not adults, had greater preference for the CS2 than controls, a result indicative of ontogenetic variation in ethanol-mediated reinforcement. During the CS1 - CS2 associative phase, paired adolescents given 2.0 g/kg ethanol wall-climbed more than controls. Blood and brain ethanol levels associated with the 0.5 and 2.0 g/kg doses at the onset of each conditioning phase did not differ substantially across age, with mean BECs of 38 and 112 mg %. Conclusions These data indicate age-related differences between adolescent and adult rats in terms of sensitivity to ethanol’s motivational effects. Adolescents exhibit high sensitivity for ethanol’s appetitive effects. These animals also showed EtOH-mediated behavioral activation during the second-order conditioning phase. The SOC preparation provides a valuable conditioning model for assessing ethanol’s motivational effects across ontogeny. PMID:18782343

  6. Statistical theory of synaptic connectivity in the neocortex

    NASA Astrophysics Data System (ADS)

    Escobar, Gina

    Learning and long-term memory rely on plasticity of neural circuits. In adult cerebral cortex plasticity can be mediated by modulation of existing synapses and structural reorganization of circuits through growth and retraction of dendritic spines. In the first part of this thesis, we describe a theoretical framework for the analysis of spine remodeling plasticity. New synaptic contacts appear in the neuropil where gaps between axonal and dendritic branches can be bridged by dendritic spines. Such sites are termed potential synapses. We derive expressions for the densities of potential synapses in the neuropil. We calculate the ratio of actual to potential synapses, called the connectivity fraction, and use it to find the number of structurally different circuits attainable with spine remodeling. These parameters are calculated in four systems: mouse occipital cortex, rat hippocampal area CA1, monkey primary visual (V1), and human temporal cortex. The neurogeometric results indicate that a dendritic spine can choose among an average of 4-7 potential targets in rodents, while in primates it can choose from 10-20 potential targets. The potential of the neuropil to undergo circuit remodeling is found to be highest in rat CA1 (4.9-6.0 nats/mum 3) and lowest in monkey V1 (0.9-1.0 nats/mum3). We evaluate the lower bound of neuron selectivity in the choice of synaptic partners and find that post-synaptic excitatory neurons in rodents make synaptic contacts with more than 21-30% of pre-synaptic axons encountered with new spine growth. Primate neurons appear to be more selective, making synaptic connections with more than 7-15% of encountered axons. Another plasticity mechanism is included in the second part of this work: long-term potentiation and depression of excitatory synaptic connections. Because synaptic strength is correlated with the size of the synapse, the former can be inferred from the distribution of spine head volumes. To this end we analyze and compare 166

  7. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. PMID:22484141

  8. Ablating Adult Neurogenesis in the Rat Has No Effect on Spatial Processing: Evidence from a Novel Pharmacogenetic Model

    PubMed Central

    Groves, James O.; Leslie, Isla; Huang, Guo-Jen; McHugh, Stephen B.; Taylor, Amy; Mott, Richard; Munafò, Marcus; Bannerman, David M.; Flint, Jonathan

    2013-01-01

    The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis. PMID:24039591

  9. Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model.

    PubMed

    Groves, James O; Leslie, Isla; Huang, Guo-Jen; McHugh, Stephen B; Taylor, Amy; Mott, Richard; Munafò, Marcus; Bannerman, David M; Flint, Jonathan

    2013-01-01

    The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis. PMID:24039591

  10. Binge ethanol intoxication heightens subsequent ethanol intake in adolescent, but not adult, rats.

    PubMed

    Fabio, María Carolina; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2014-04-01

    A question still to be answered is whether ethanol initiation has a greater effect on ethanol consumption if it occurs during adolescence than in adulthood. This study assessed the effect of ethanol initiation during adolescence or adulthood on voluntary ethanol consumption when animals were still within the same age range. Adolescent or adult rats were given 5, 2, or 0 ethanol exposures. The animals were tested for ethanol consumption through two-bottle choice tests, before undergoing a 1-week deprivation. A two-bottle assessment was conducted after the deprivation. Adolescents, but not adults, given two ethanol administrations during initiation exhibited significantly higher ethanol intake during the pre-deprivation period. These adolescents also exhibited a threefold increase in ethanol intake after 7 days of drug withdrawal, when compared with controls. These findings suggest that very brief experience with binge ethanol intoxication in adolescence, but not in adulthood, impacts later predisposition to drink. PMID:23341340

  11. A detailed viscoelastic characterization of the P17 and adult rat brain.

    PubMed

    Elkin, Benjamin S; Ilankovan, Ashok I; Morrison, Barclay

    2011-11-01

    Brain is a morphologically and mechanically heterogeneous organ. Although rat brain is commonly used as an experimental neurophysiological model for various in vivo biomechanical studies, little is known about its regional viscoelastic properties. To address this issue, we have generated viscoelastic mechanical property data for specific anatomical regions of the P17 and adult rat brain. These ages are commonly used in rat experimental models. We measured mechanical properties of both white and gray matter regions in coronal slices with a custom-designed microindentation device performing stress-relaxation indentations to 10% effective strain. Shear moduli calculated for short (100?ms), intermediate (1?sec), and long (20?sec) time points, ranged from ?1?kPa for short term moduli to ?0.4?kPa for long term moduli. Both age and anatomic region were significant factors affecting the time-dependent shear modulus. White matter regions and regions of the cerebellum were much more compliant than those of the hippocampus, cortex, and thalamus. Linear viscoelastic models (Prony series, continuous phase lag, and a power law model) were fit to the time-dependent shear modulus data. All models fit the data equally with no significant differences between them (F-test; p>0.05). The F-test was also used to statistically determine that a Prony series with three time-dependent parameters accurately fit the data with no added benefit from additional terms. The age- and region-dependent rat brain viscoelastic properties presented here will help inform future biomechanical models of the rat brain with specific and accurate regional mechanical property data. PMID:21341982

  12. Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel insulinotropic mediator

    PubMed Central

    Shao, Chunhong; Zucker, Irving H.

    2013-01-01

    In the present study, we evaluated the relative abundance of angiotensin type 2 receptor (AT2R) protein in various tissues of adult rats. We found that pancreatic islets expressed the highest AT2R protein compared with all other tissues. Accordingly, we then determined the functional significance of AT2R in the endocrine pancreas in in vivo and in vitro experiments by using angiotensin II (ANG II) alone, losartan (Los; AT1R antagonist), compound 21 (C21; AT2R agonist), and PD-123319 (PD; AT2R antagonist). Experiments carried out in rats indicated that, 1) ANG II treatment significantly increased plasma insulin concentration (1.51 ± 0.20 vs. 0.82 ± 0.14 ng/ml, n = 7, P < 0.05) in the fed state. This insulinotropic effect was further augmented by combined treatment with ANG II + Los (2.31 ± 0.25 ng/ml, n = 7, P < 0.01). C21 also elevated insulin levels (2.13 ± 0.20 ng/ml, n = 7, P < 0.01), which was completely abolished by PD. 2) ANG II impaired glucose tolerance, whereas ANG II + Los or C21 improved this function. 3) All treated rats displayed an enhanced insulin secretory response to a glucose challenge. 4) All treated rats displayed upregulated proinsulin 2 mRNA and insulin protein expression in the pancreas. In in vitro experiments using INS-1E cells and isolated rat islets, we found that AT2R activation significantly improved insulin biosynthesis and secretion. These results suggest that the AT2R functions as an insulinotropic mediator. AT2R and its downstream signaling pathways may be potential therapeutic targets for diabetes. PMID:24085035

  13. Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats

    PubMed Central

    KONG, Lingfa; WEI, Quanwei; FEDAIL, Jaafar Sulieman; SHI, Fangxiong; NAGAOKA, Kentaro; WATANABE, Gen

    2015-01-01

    Thyroid hormones and oxidative stress play significant roles in the normal functioning of the female reproductive system. Nitric oxide (NO), a free radical synthesized by nitric oxide synthases (NOS), participates in the regulation of thyroid function and is also a good biomarker for assessment of the oxidative stress status. Therefore, the purpose of this study was to investigate effects of thyroid hormones on uterine antioxidative status in young adult rats. Thirty immature female Sprague-Dawley rats were randomly divided into three groups: control, hypothyroid (hypo-T) and hyperthyroid (hyper-T). The results showed the body weights decreased significantly in both the hypo-T and hyper-T groups and that uterine weights were decreased significantly in the hypo-T group. The serum concentrations of total triiodothyronine (T3) and thyroxine (T4), as well as estradiol (E2), were significantly decreased in the hypo-T group, but increased in the hyper-T group. The progesterone (P4) concentrations in the hypo- and hyperthyroid rats markedly decreased. Immunohistochemistry results provided evidence that thyroid hormone nuclear receptor α/β (TRα/β) and three NOS isoforms were located in different cell types of rat uteri. The NO content and total NOS and inducible NOS (iNOS) activities were markedly diminished in the hypo-T group but increased in the hyper-T group. Moreover, the activities of both glutathione peroxidase (GSH-Px) and catalase (CAT) exhibited significant decreases and increases in the hypo-T and hyper-T groups, respectively. The malondialdehyde (MDA) contents in both the hypo-T and hyper-T groups showed a significant increase. Total superoxide dismutase (T-SOD) activity in the hypo- and hyper-T rats markedly decreased. In conclusion, these results indicated that thyroid hormones have an important influence on the modulation of uterine antioxidative status. PMID:25797533

  14. Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition.

    PubMed

    Boaventura, G; Casimiro-Lopes, G; Pazos-Moura, C C; Oliveira, E; Lisboa, P C; Moura, E G

    2013-10-01

    The inhibition of maternal prolactin production in late lactation leads to metabolic syndrome and hypothyroidism in adult offspring. Physical training is a therapeutic strategy that could prevent or reverse this condition. We evaluated the effects of a short-duration low-intensity running wheel training program on the metabolic and hormonal alterations in rats. Lactating Wistar rats were treated with bromocriptine (Bro, 1 mg twice a day) or saline on days 19, 20, and 21 of lactation, and the training of offspring began at 35 days of age. Offspring were divided into sedentary and trained controls (C-Sed and C-Ex) and sedentary and trained Bro-treated rats (Bro-Sed and Bro-Ex). Chronic exercise delayed the onset of weight gain in Bro-Ex offspring, and the food intake did not change during the experimental period. At 180 days, visceral fat mass was higher (+46%) in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running capacity was higher in trained animals. Most parameters observed in the Bro-Sed offspring were consistent with hypothyroidism and metabolic syndrome and were reversed in the Bro-Ex group. Chronic exercise did not influence the muscle glycogen in the C-Ex group; however, liver glycogen was higher (+30%) in C-Ex group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher plasma lactate dehydrogenase levels, indicating skeletal muscle damage and intolerance of the training program. Low-intensity chronic training is able to normalize many clinical aspects in Bro animals; however, these animals might have had a lower threshold for exercise adaptation than the control rats. PMID:23863192

  15. Ovariectomy Results in Variable Changes in Nociception, Mood and Depression in Adult Female Rats

    PubMed Central

    Li, Li-Hong; Wang, Zhe-Chen; Yu, Jin; Zhang, Yu-Qiu

    2014-01-01

    Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way. PMID:24710472

  16. Chronic intermittent ethanol exposure produces persistent anxiety in adolescent and adult rats

    PubMed Central

    Van Skike, Candice E.; Diaz-Granados, Jaime L.; Matthews, Douglas B.

    2014-01-01

    Background Ethanol dependence and tolerance in the adult are marked by increased function of NMDA receptors and decreased function of GABAA receptors that coincides with altered receptor subunit expression in specific brain regions. Adolescents often use ethanol at levels greater than adults, yet the receptor subunit expression profiles following chronic intermittent ethanol (CIE) exposure in adolescents are not known. Persistent age-dependent changes in receptor subunit alterations coupled with withdrawal-related anxiety may help explain the increase in alcohol abuse following adolescent experimentation with the drug. Methods Adolescent and adult rats received 10 intraperitoneal administrations of 4.0 g/kg ethanol or saline every 48 hours. At either 24 hours or 12 days after the final exposure, anxiety-like behavior was assessed on the elevated plus maze and tissue was collected. Western blotting was used to assess changes in selected NMDA and GABAA receptor subunits in whole cortex and bilateral hippocampus. Results CIE exposure yields a persistent increase in anxiety-like behavior in both age groups. However, selected NMDA and GABAA receptor subunits were not differentially altered by this CIE exposure paradigm in adolescents or adults. Conclusions CIE exposure produced persistent anxiety-like behavior, which has important implications for alcohol cessation. Given the reported behavioral and neuropeptide expression changes in response to this dose of ethanol, it is important for future work to consider the circumstances under which these measures are altered by ethanol exposure. PMID:25684048

  17. Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function.

    PubMed

    Eyles, Darryl W; Rogers, Fiona; Buller, Kathryn; McGrath, John J; Ko, Pauline; French, Kathryn; Burne, Thomas H J

    2006-09-01

    Developmental vitamin D deficiency (DVD) has been shown to alter the orderly pattern of brain development. Even though the period of vitamin D deficiency is restricted to gestation this is sufficient to induce behavioural abnormalities in the adult offspring consistent with those seen in many animal models of schizophrenia. Given that some of these behavioural alterations could also be an indirect result of either impaired maternal hypothalamic pituitary axis (HPA) function (which in turn could influence maternal care) or the result of a permanent alteration in HPA function in the adult offspring we have examined HPA status in both maternal animals and adult offspring. In this study we have established that HPA function is normal in the maternally vitamin D deficient rat. We replicate the behavioural phenotype of hyperlocomotion whilst establishing that HPA function is also unchanged in the adult male offspring. We conclude that the behavioural alterations induced by DVD deficiency are due to some adverse event in brain development rather than via an alteration in stress response. PMID:16890375

  18. Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats.

    PubMed

    Martí-Carbonell, Maria Assumpció; Garau, Adriana; Sala-Roca, Josefina; Balada, Ferran

    2012-01-01

    Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups. PMID:23093010

  19. Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

    PubMed

    Hordeaux, J; Dubreil, L; Deniaud, J; Iacobelli, F; Moreau, S; Ledevin, M; Le Guiner, C; Blouin, V; Le Duff, J; Mendes-Madeira, A; Rolling, F; Cherel, Y; Moullier, P; Colle, M-A

    2015-04-01

    Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we tested intravenous (IV) or intrathecal (that is, in the cerebrospinal fluid (CSF)) delivery of a rAAVrh10-egfp vector in adult and neonate rats and studied the effect of the age at injection on neurotropism. IV delivery is more efficient in neonates and targets predominantly Purkinje cells of the cerebellum and sensory neurons of the spinal cord and dorsal root ganglia. A single intra-CSF administration of AAVrh10, single strand or oversized self-complementary, is efficient for the targeting of neurons in the cerebral hemispheres, cerebellum, brainstem and spinal cord. Green fluorescent protein (GFP) expression is more widespread in neonates when compared with adults. More than 50% of motor neurons express GFP in the three segments of the spinal cord in neonates and in the cervical and thoracic regions in adults. Neurons are almost exclusively transduced in neonates, whereas neurons, astrocytes and rare oligodendrocytes are targeted in adults. These results expand the possible routes of delivery of AAVrh10, a serotype that has shown efficacy and safety in clinical trials concerning neurodegenerative diseases. PMID:25588740

  20. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  1. Developmental exposure to polychlorinated biphenyls PCB153 or PCB126 impairs learning ability in young but not in adult rats.

    PubMed

    Piedrafita, Blanca; Erceg, Slaven; Cauli, Omar; Monfort, Pilar; Felipo, Vicente

    2008-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants present in the food chain and in human blood and milk. Exposure to PCBs during pregnancy and lactation leads to cognitive impairment in children. The underlying mechanisms remain unclear. Some PCBs are endocrine disrupters. The aim of this work was to assess whether exposure of rats to PCB126 (dioxin-like) or PCB153 (non-dioxin-like) during pregnancy and lactation affects the ability of the pups to learn a Y maze conditional discrimination task and/or the function of the glutamate-nitric oxide (NO)-cGMP pathway in brain in vivo when the rats are young (3 months) or adult (7-8 months). After finishing the learning experiments, the function of the pathway was analysed in the same rats by in vivo brain microdialysis. The results obtained show that perinatal exposure to PCB153 or PCB126: (1) impairs learning ability in young but not in adult rats, (2) impairs the glutamate-NO-cGMP pathway function in cerebellum in vivo in young but not in adult rats and (3) affect these parameters in males and females similarly. PCB126 is around 10 000-fold more potent than PCB153. In control rats the function of the glutamate-NO-cGMP pathway and learning ability are lower in adult than in young rats. These age-related differences are not present in rats exposed to PCBs. The impairment of the glutamate-NO-cGMP pathway function induced at young age by developmental exposure to the PCBs could be one of the mechanisms contributing to the cognitive impairment found in children whose mothers ingested PCB-contaminated food during pregnancy and lactation. PMID:18093177

  2. Sexual odor discrimination and physiological profiles in adult male rats after a neonatal, short term, reversible nasal obstruction.

    PubMed

    Thornton, S N; Padzys, G S; Trabalon, M

    2014-05-01

    The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult. PMID:24769524

  3. TBR1 regulates autism risk genes in the developing neocortex.

    PubMed

    Notwell, James H; Heavner, Whitney E; Darbandi, Siavash Fazel; Katzman, Sol; McKenna, William L; Ortiz-Londono, Christian F; Tastad, David; Eckler, Matthew J; Rubenstein, John L R; McConnell, Susan K; Chen, Bin; Bejerano, Gill

    2016-08-01

    Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the nine ASD genes examined, seven were misexpressed in the cortices of Tbr1 knockout mice, including six with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development. PMID:27325115

  4. AMPA receptor regulation during synaptic plasticity in hippocampus and neocortex

    PubMed Central

    Lee, Hey-Kyoung; Kirkwood, Alfredo

    2011-01-01

    Discovery of long-term potentiation (LTP) in the dentate gyrus of the rabbit hippocampus by Bliss and Lømo opened up a whole new field to study activity-dependent long-term synaptic modifications in the brain. Since then hippocampal synapses have been a key model system to study the mechanisms of different forms of synaptic plasticity. At least for the postsynaptic forms of LTP and long-term depression (LTD), regulation of AMPA receptors (AMPARs) has emerged as a key mechanism. While many of the synaptic plasticity mechanisms uncovered in at the hippocampal synapses apply to synapses across diverse brain regions, there are differences in the mechanisms that often reveal the specific functional requirements of the brain area under study. Here we will review AMPAR regulation underlying synaptic plasticity in hippocampus and neocortex. The main focus of this review will be placed on postsynaptic forms of synaptic plasticity that impinge on the regulation of AMPARs using hippocampal CA1 and primary sensory cortices as examples. And through the comparison, we will highlight the key similarities and functional differences between the two synapses. PMID:21856433

  5. Development and Distribution of Neuronal Cilia in Mouse Neocortex

    PubMed Central

    Arellano, Jon I.; Guadiana, Sarah M.; Breunig, Joshua J.; Rakic, Pasko; Sarkisian, Matthew R.

    2011-01-01

    Neuronal primary cilia are not generally recognized, but they are considered to extend from most, if not all, neurons in the neocortex. However, when and how cilia develop in neurons are not known. This study used immunohistochemistry for adenylyl cyclase III (ACIII), a marker of primary cilia, and electron microscopic analysis to describe the development and maturation of cilia in mouse neocortical neurons. Our results indicate that ciliogenesis is initiated in late fetal stages after neuroblast migration, when the mother centriole docks with the plasma membrane, becomes a basal body, and grows a cilia bud that we call a procilium. This procilium consists of a membranous protrusion extending from the basal body but lacking axonemal structure and remains undifferentiated until development of the axoneme and cilia elongation starts at about postnatal day 4. Neuronal cilia elongation and final cilia length depend on layer position, and the process extends for a long time, lasting 8–12 weeks. We show that, in addition to pyramidal neurons, inhibitory interneurons also grow cilia of comparable length, suggesting that cilia are indeed present in all neocortical neuron subtypes. Furthermore, the study of mice with defective ciliogenesis suggested that failed elongation of cilia is not essential for proper neuronal migration and laminar organization or establishment of neuronal polarity. Thus, the function of this organelle in neocortical neurons remains elusive. PMID:22020803

  6. Effects of Extremely Low Frequency Electromagnetic Fields on Vascular Permeability of Circumventricular Organs in the Adult Rat

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Mercado, Y. K.; Cañedo-Dorantes, L.; Bañuelos-Pineda, J.; Serrano-Luna, G.; Feria-Velasco, A.

    2008-08-01

    The present work deals with the effects of extremely low frequency electromagnetic fields (ELF-EMF) on blood vessels permeability to non liposoluble substances of the circumventricular organs (CVO) of adult rats. Male Wistar adult rats were exposed to ELF-EMF and vascular permeability to colloidal carbon was investigated with the use of histological techniques. Results were compared to corresponding data from sham-exposed and control groups of animals. Exposure to ELF-EMF increased the CVO vascular permeability to colloidal carbon intravascularly injected, particularly in the subfornical organ, the median eminence, the pineal gland and the area postrema.

  7. Environmental Enrichment Protects the Retina from Early Diabetic Damage in Adult Rats

    PubMed Central

    Dorfman, Damián; Aranda, Marcos L.; González Fleitas, María Florencia; Chianelli, Mónica S.; Fernandez, Diego C.; Sande, Pablo H.; Rosenstein, Ruth E.

    2014-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan's blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats. PMID:25004165

  8. Ethanol-Induced Alterations in Purkinje Neuron Dendrites in Adult and Aging Rats: a Review.

    PubMed

    Dlugos, Cynthia A

    2015-08-01

    Uncomplicated alcoholics suffer from discrete motor dysfunctions that become more pronounced with age. These deficits involve the structure and function of Purkinje neurons (PN), the sole output neurons from the cerebellar cortex. This review focuses on alterations to the PN dendritic arbor in the adult and aging Fischer 344 rat following lengthy alcohol consumption. It describes seminal studies using the Golgi-Cox method which proposed a model for ethanol-induced dendritic regression. Subsequent ultrastructural studies of PN dendrites showed dilation of the extensive smooth endoplasmic reticulum (SER) which preceded and accompanied dendritic regression. The component of the SER that was most affected by ethanol was the sarco/endoplasmic reticulum Ca(2+) ATPase pump (SERCA) responsible for resequestration of calcium into the SER. Ethanol-induced decreases in SERCA pump levels, similar to the finding of SER dilation, preceded and occurred concomitantly with dendritic regression. Discrete ethanol-induced deficits in balance also accompanied these decreases. Ethanol-induced ER stress within the SER of PN dendrites was proposed as an underlying cause of dendritic regression. It was recently shown that increased activation of caspase 12, inherent to the ER, occurred in PN of acute slices in ethanol-fed rats and was most pronounced following 40 weeks of ethanol treatment. These findings shed new light into alcohol-induced disruption in PN dendrites providing a new model for the discrete but critical changes in motor function in aging, adult alcoholics. PMID:25648753

  9. Effects of Rolipram on Adult Rat Oligodendrocytes and Functional Recovery after Contusive Cervical Spinal Cord Injury

    PubMed Central

    Beaumont, Eric; Whitaker, Christopher M.; Burke, Darlene A.; Hetman, Michal; Onifer, Stephen M.

    2009-01-01

    Traumatic human spinal cord injury causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after SCI are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus express 3′-5′-cyclic adenosine monophosphate-dependent phosphodiesterase 4 subtypes and that their death was attenuated up to 3 days after contusive cervical spinal cord injury when rolipram, a specific inhibitor of phosphodiesterase 4, was administered. Here, we report that 1) there are more oligodendrocyte somata in the adult rat epicenter ventrolateral funiculus, 2) descending and ascending axonal conductivity in the ventrolateral funiculus improves, and that 3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical spinal cord injury when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a spinal cord injury with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with spinal cord injury. PMID:19635528

  10. Extracellular space diffusion analysis in the infant and adult rat striatum using magnetic resonance imaging.

    PubMed

    Yang, Shuangfeng; Wang, Yan; Li, Kai; Tang, Xiaolu; Zhang, Kuo; Shi, Chunyan; Han, Hongbin; Peng, Yun

    2016-10-01

    The extracellular space (ECS) in the brain provides an extrasynaptic transfer channel among neurons, axons and glial cells. It is particularly important in the early stage after birth, when angiogenesis is not yet complete and the ECS may provide the main pathway for metabolite transport. However, the characteristics of extracellular transport remain unclear. In this study, a novel magnetic resonance imaging (MRI) method was used to perform real-time visualization and quantification of diffusion in the brain ECS of infant (postnatal day 10 (P10)) and adult rats. Using a modified diffusion equation and the linear relationship between the signal intensity and the gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration, diffusion parameters were obtained; these parameters include the effective diffusion coefficient (D*), clearance rate (k'), tortuosity (λ) and the volume fraction of distribution (Vd%). There were significant differences in the diffusion parameters between P10 and adult rats. This finding provides a reference for future treatment of brain diseases using drugs administered via interstitial pathways. PMID:27296518

  11. Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus

    PubMed Central

    Wong-Goodrich, Sarah J. E.; Mellott, Tiffany J.; Glenn, Melissa J.; Blusztajn, Jan K.; Williams, Christina L.

    2008-01-01

    Prenatal choline supplementation (SUP) protects adult rats against spatial memory deficits observed after excitotoxin-induced status epilepticus (SE). To examine the mechanism underlying this neuroprotection, we determined the effects of SUP on a variety of hippocampal markers known to change in response to SE and thought to underlie ensuing cognitive deficits. Adult offspring from rat dams that received either a Control or SUP diet on embryonic days 12–17 were administered saline or kainic acid (i.p.) to induce SE and were euthanized 16 days later. SUP markedly attenuated seizure-induced hippocampal neurodegeneration, dentate cell proliferation, hippocampal GFAP mRNA expression levels, prevented the loss of hippocampal GAD65 protein and mRNA expression, and altered growth factor expression patterns. SUP also enhanced pre-seizure hippocampal levels of BDNF, NGF, and IGF-1, which may confer a neuroprotective hippocampal microenvironment that dampens the neuropathological response to and/or helps facilitate recovery from SE to protect cognitive function. PMID:18353663

  12. Subacute toxicity assessment of diflubenzuron, an insect growth regulator, in adult male rats.

    PubMed

    de Barros, Aline Lima; Cavalheiro, Gabriela Finoto; de Souza, Alexsandra Vila Maior; Traesel, Giseli Karenina; Anselmo-Franci, Janete A; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

    2016-04-01

    Diflubenzuron (DFB), an insecticide and acaricide insect growth regulator, can be used in agriculture against insect predators and in public health programs, to control insects and vectors, mainly Aedes aegypti larvae. Due to the lack of toxicological assessments of this compound, the objective of the present study was to evaluate the toxicological effects of subacute exposure to the DFB insecticide in adult male rats. Adult male rats were exposed (gavage) to 0, 2, 4, or 8 mg/kg of DFB for 28 days. No clinical signs of toxicity were observed in the DFB-treated animals of the experimental groups. However, there was an increase in serum levels of alanine aminotransferase in the group that received 8 mg/kg/DFB/day and urea at doses of 4 and 8 mg/kg/DFB/day, without altering other biochemical or hematological parameters. The subacute exposure to the lowest dose of DFB caused significant decrease in testis weight, daily sperm production, and in number of sperm in the epididymis in relation to the control group. However, no alterations were observed in the sperm morphology, testicular, epididymis, liver and kidney histology, or testosterone levels. These findings unveiled the hazardous effects of DFB on male reproduction after the subacute exposure and special attention should be addressed to the effects of low doses of this pesticide. PMID:25266294

  13. The effect of omega-3 on cognition in hypothyroid adult male rats.

    PubMed

    Abd Allah, Eman S H; Gomaa, Asmaa M S; Sayed, Manal M

    2014-09-01

    Thyroid hormones and omega-3 are essential for normal brain functions. Recent studies have suggested that omega-3 may protect against the risk of dementia. The aim of this study was to investigate the effect of hypothyroidism on spatial learning and memory in adult male rats, the underlying mechanisms and the possible therapeutic value of omega-3 supplementation. Thirty male rats were divided into three groups; control, hypothyroid and omega-3 treated. Hypothyroidism induced significant deficits in working and reference memories in radial arm maze, retention deficits in passive avoidance test and impaired intermediate and long-term memories in novel object recognition test. Serum total antioxidant capacity (TAC) and hippocampal serotonin and γ-aminobutyric acid (GABA) levels were decreased in the hypothyroid group as compared to the control group. Moreover, the hippocampus of hypothyroid rats showed marked structural changes as diffuse vacuolar degeneration and distortion of the pyramidal cells. Immunohistochemistry showed that the expression of Cav1.2 (the voltage dependent LTCC alpha 1c subunit) protein was increased in the hypothyroid group as compared to the control group. Omega-3 supplementation ameliorated memory deficits, increased TAC, decreased the structural changes and decreased the expression of Cav1.2 protein. In conclusion omega-3 could be useful as a neuroprotective agent against hypothyroidism-induced cognitive impairment. PMID:25183510

  14. Effects of different exercise protocols on ethanol-induced spatial memory impairment in adult male rats.

    PubMed

    Hashemi Nosrat Abadi, T; Vaghef, L; Babri, S; Mahmood-Alilo, M; Beirami, M

    2013-06-01

    Chronic ethanol consumption is often accompanied by numerous cognitive deficits and may lead to long-lasting impairments in spatial learning and memory. The aim of the present study was to evaluate the therapeutic potential of regular treadmill exercise on hippocampal-dependent memory in ethanol-treated rats. Spatial memory was tested in a Morris Water Maze task. Adult male Wistar rats were exposed to ethanol (4 g/kg, 20% v/v for 4 weeks) and effects of three exercise protocols (pre-ethanol, post-ethanol and pre-to-post-ethanol treatment) were examined. Results showed that ethanol exposure resulted in longer escape latencies during the acquisition phase of the Morris Water Maze task. Moreover, all three exercise protocols significantly decreased the latency to locate the hidden platform. During the probe trial, ethanol led to decreased time spent in the target quadrant. In contrast, performance on the probe trial was significantly better in the rats that had done the post- and pre-to-post-ethanol, but not pre-ethanol, exercises. These findings suggest that treadmill running can attenuate the adverse effects of chronic ethanol exposure on spatial memory, and may serve as a non-pharmacological alcohol abuse treatment. PMID:23683528

  15. Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

    NASA Technical Reports Server (NTRS)

    Picklo, M. J.; Wiley, R. G.; Lonce, S.; Lappi, D. A.; Robertson, D.

    1995-01-01

    Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

  16. Ghrelin stimulates milk intake by affecting adult type feeding behaviour in postnatal rats.

    PubMed

    Piao, H; Hosoda, H; Kangawa, K; Murata, T; Narita, K; Higuchi, T

    2008-03-01

    The influence of ghrelin on feeding behaviour during infancy is unknown. To determine whether ghrelin influences milk intake in rat pups, newborn rats received a single i.p. injection of either rat ghrelin (100 microg/kg) or rabbit anti-ghrelin immunoglobulin G (100 microg/kg) every 5 days from postpartum day 5 to day 30 (P5-P30). Milk intake was then assessed by body weight gain following a 2-h suckling period. Ghrelin significantly increased weight gain relative to vehicle-injected controls in P20, P25 and P30 pups, but not in younger animals. Similarly, after 8 h of milk restriction, anti-ghrelin injections significantly decreased weight gain in P25 and P30, but not in younger pups. Interestingly, however, ghrelin did increase independent feeding in P10 and P15 pups using a paradigm in which pups consumed milk from a milk-soaked paper towel. We therefore conclude that ghrelin stimulates milk intake at an early postnatal stage, primarily by affecting adult-type feeding behaviour. PMID:18194428

  17. Oral administration of leaf extracts of Momordica charantia affect reproductive hormones of adult female Wistar rats

    PubMed Central

    Adewale, Osonuga Odusoga; Oduyemi, Osonuga Ifabunmi; Ayokunle, Osonuga

    2014-01-01

    Objective To determine the effect of graded doses of aqueous leaf extracts of Momordica charantia on fertility hormones of female albino rats. Methods Twenty adult, healthy, female Wistar rats were divided into four groups: low dose (LD), moderate dose (MD) and high dose (HD) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. Result Estrogen levels reduced by 6.40 nmol/L, 10.80 nmol/L and 28.00 nmol/L in the LD, MD and HD groups respectively while plasma progesterone of rats in the LD, MD and HD groups reduced by 24.20 nmol/L, 40.8 nmol/L and 59.20 nmol/L respectively. Conclusion Our study has shown that the antifertility effect of Momordica charantia is achieved in a dose dependent manner. Hence, cautious use of such medication should be advocated especially when managing couples for infertility. PMID:25183143

  18. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

    PubMed Central

    KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

    2015-01-01

    The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

  19. The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats

    PubMed Central

    Dickerson, Sarah M.; Walker, Deena M.; Reveron, Maria E.; Duvauchelle, Christine L.; Gore, Andrea C.

    2009-01-01

    Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug ±-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal (HPG) reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA or saline either once (acute) or for 20 days (chronic), and were euthanized 7 days following last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone (LH) concentrations, and serum testosterone levels, as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the HPG axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. PMID:18309234

  20. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Brown, Ronald P.; Fisher, Jeffrey W.

    2011-09-15

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral

  1. Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia

    PubMed Central

    Prieto-Lloret, Jesus; Ramirez, Maria; Olea, Elena; Moral-Sanz, Javier; Cogolludo, Angel; Castañeda, Javier; Yubero, Sara; Agapito, Teresa; Gomez-Niño, Angela; Rocher, Asuncion; Rigual, Ricardo; Obeso, Ana; Perez-Vizcaino, Francisco; González, Constancio

    2015-01-01

    Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55–60% O2 for the last 5–6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2-sensitivity of K+ currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life. Key points Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is

  2. Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

    PubMed Central

    Tajuddin, Nuzhath; Moon, Kwan-Hoon; Marshall, S. Alex; Nixon, Kimberly; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2014-01-01

    Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  3. Behavioral effects of corpus callosum transection and environmental enrichment in adult rats.

    PubMed

    Miu, Andrei C; Heilman, Renata M; Paşca, Sergiu P; Stefan, Catrinel A; Spânu, Florina; Vasiu, Renata; Olteanu, Adrian I; Miclea, Mircea

    2006-09-15

    A common assumption about the corpus callosum transection (CCX) is that it only affects behaviors heavily relying on interhemispheric communication. However, cerebral laterality is ubiquitous across motor and perceptual, cognitive and emotional domains, and the corpus callosum is important for its establishment. Several recent studies showed that the partial denervation of the sensorimotor isocortex through CCX derepressed neural growth processes that were sensitive to motor demand (experience-dependent neural plasticity). We investigated whether the facilitatory effects of CCX on cortical neural plasticity, shaped by differential housing, extended beyond the motor domain. Adult rats were housed in enriched (EE), standard (SE) or impoverished environments (IE) for 10 weeks, that is, 2 weeks before they underwent CCX or sham surgery, and, then, 8 weeks throughout the experiments. After they recovered from surgery, the behavioral performance of rats was tested using open-field, spontaneous alternation in the T-maze, paw preference, Morris water maze, and tone fear conditioning. The results indicated that the effects of CCX and housing on open-field behavior were independent, with CCX increasing the time spent in the center of the field at the beginning of the observation (i.e., emotionality), and EE and IE increasing rearing (emotionality) and reducing teeth-chattering (habituation), respectively. CCX reduced the frequency of spontaneous alternation, denoting spatial working memory deficits, while housing did not influence this performance. Neither CCX, nor housing significantly affected paw preference lateralization, although CCX was associated with a leftward bias in paw preference. In the Morris water maze, housing had effects on spatial acquisition, while CCX reduced activity, without interfering with spatial memory. CCX did not influence tone fear conditioning, but context fear conditioning seemed to benefit from EE. We conclude that CCX in adult rats has subtle

  4. Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat.

    PubMed

    Loy, David N; Talbott, Jason F; Onifer, Stephen M; Mills, Michael D; Burke, Darlene A; Dennison, Jessica B; Fajardo, Lili C; Magnuson, David S K; Whittemore, Scott R

    2002-10-01

    Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter. However, dorsal hemisections that interrupt dorsal columns/dorsal corticospinal tract (DC/CST) and DLF pathways do not produce persistent, severe locomotor deficits in the adult rat. We studied the contributions of myelinated tracts in the DLF and DC/CST to overground locomotion following complete conduction blockade of axons in the ventrolateral funiculus (VLF), a region important for locomotor movements and for transcranial magnetic motor-evoked potentials (tcMMEP). Animals received ethidium bromide plus photon irradiation to produce discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, combined VLF + DLF, or combined VLF + DC/CST. Open-field BBB scores and tcMMEPs were studied at 1, 2, 3, and 4 weeks postlesion. VLF lesions resulted in mean BBB scores of 17 at 4 weeks. VLF + DC/CST and VLF + DLF lesions resulted in mean BBB scores of 15.9 and 11.1, respectively. TcMMEPs were absent in all lesion types confirming VLF conduction blockade throughout the study. Our data indicate that significant contributions to locomotion from myelinated pathways within the rat DLF can be revealed when combined with simultaneous compromise of the VLF. PMID:12429203

  5. Alpha actin isoforms expression in human and rat adult cardiac conduction system.

    PubMed

    Orlandi, Augusto; Hao, Hiroyuki; Ferlosio, Amedeo; Clément, Sophie; Hirota, Seiichi; Spagnoli, Luigi Giusto; Gabbiani, Giulio; Chaponnier, Christine

    2009-04-01

    In the adult heart, cardiac muscle comprises the working myocardium and the conduction system (CS). The latter includes the sinoatrial node (SAN), the internodal tract or bundle (IB), the atrioventricular node (AVN), the atrioventricular bundle (AVB), the bundle branches (BB) and the peripheral Purkinje fibers (PF). Most of the information concerning the phenotypic features of CS tissue derives from the characterization of avian and rodent developing hearts; data concerning the expression of actin isoforms in adult CS cardiomyocytes are scarce. Using specific antibodies, we investigated the distribution of alpha-skeletal (alpha-SKA), alpha-cardiac (alpha-CA), alpha-smooth muscle (alpha-SMA) actin isoforms and other muscle-typical proteins in the CS of human and rat hearts at different ages. SAN and IB cardiomyocytes were characterized by the presence of alpha-SMA, alpha-CA, calponin and caldesmon, whereas alpha-SKA and vimentin were absent. Double immunofluorescence demonstrated the co-localisation of alpha-SMA and alpha-CA in I-bands of SAN cardiomyocytes. AVN, AVB, BB and PF cardiomyocytes were alpha-SMA, calponin, caldesmon and vimentin negative, and alpha-CA and alpha-SKA positive. No substantial differences in actin isoform distribution were observed in human and rat hearts, except for the presence of isolated subendocardial alpha-SMA positive cardiomyocytes co-expressing alpha-CA in the ventricular septum of the rat. Aging did not influence CS cardiomyocyte actin isoform expression profile. These findings support the concept that cardiomyocytes of SAN retain the phenotype of a developing myogenic cell throughout the entire life span. PMID:19281784

  6. Hormone responsiveness of cultured Sertoli cells obtained from adult rats after their rapid isolation under less harsh conditions.

    PubMed

    Gautam, M; Bhattacharya, I; Devi, Y S; Arya, S P; Majumdar, S S

    2016-05-01

    During adulthood, testicular Sertoli cells (Sc) coordinate all stages of germ cell (Gc) development involved in sperm production. However, our understanding about the functions of adult Sc is limited because of the difficulties involved in the process of isolating these cells from the adult testis, mainly because of the presence of large number of advanced Gc which interfere with Sc isolation at this age. Most of our knowledge about Sc function are derived from studies which used pre-pubertal rat Sc (18 ± 2-day old) as it is easy to isolate and culture Sc at this age. To this end, we established a less time consuming and less harsh procedure of isolating Sc from adult (60 days of age) rat testis for facilitating research on Sc-mediated regulation of spermatogenesis during adulthood. The cells were isolated using collagenase digestion at higher temperature, reducing the exposure time of cells to the enzyme. Step-wise digestion with intermittent removal of small clusters of tissue helped in increasing the yield of Sc. Isolated Sc were cultured and treated with FSH and testosterone (T) to evaluate their hormone responsiveness in terms of lactate, E2 , cAMP production. Adult Sc were found to be active and produced high amounts of lactate in a FSH-independent manner. FSH-mediated augmentation of cAMP and E2 production by adult Sc was less as compared with that by pre-pubertal Sc obtained from 18-day-old rats. Androgen-binding ability of adult Sc was significantly higher than pre-pubertal Sc. Although T treatment remarkably augmented expression of Claudin 11, it failed to augment lactate production by adult Sc. This efficient and rapid procedure for isolation and culture of functionally viable adult rat Sertoli cells may pave the way for determining their role in regulation and maintenance of spermatogenesis. PMID:26991307

  7. The Impact of Adult Vitamin D Deficiency on Behaviour and Brain Function in Male Sprague-Dawley Rats

    PubMed Central

    Turner, Karly M.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2013-01-01

    Background Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Methods Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. Results AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. Conclusions AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour. PMID:23951200

  8. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg;P=0.007), and nitric oxide synthase inhibition (withl-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment withl-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%;P<0.05), and this difference could be normalized byl-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. PMID:26928803

  9. Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats.

    PubMed

    Lazzaretti, Camilla; Kincheski, Grasielle Clotildes; Pandolfo, Pablo; Krolow, Rachel; Toniazzo, Ana Paula; Arcego, Danusa Mar; Couto-Pereira, Natividade de Sá; Zeidán-Chuliá, Fares; Galvalisi, Martin; Costa, Gustavo; Scorza, Cecilia; Souza, Tadeu Mello E; Dalmaz, Carla

    2016-03-01

    Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood. PMID:26620193

  10. Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

    PubMed

    Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

    2011-07-01

    Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. PMID:21185124

  11. Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

    PubMed

    Šlamberová, R; Pometlová, M; Schutová, B; Hrubá, L; Macúchová, E; Nová, E; Rokyta, R

    2012-01-01

    Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test. PMID:23130898

  12. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    SciTech Connect

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of (/sup 14/C)valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements.

  13. A search for residual behavioral effects of trichloroethylene (TCE) in rats exposed as young adults.

    PubMed

    Oshiro, Wendy M; Krantz, Q Todd; Bushnell, Philip J

    2004-01-01

    Trichloroethylene (TCE) is an organic solvent with robust acute effects on the nervous system, but poorly documented long-term effects. This study employed a signal detection task (SDT) to assess the persistence of effects of repeated daily inhalation of TCE on sustained attention in rats. Adult male Long-Evans rats inhaled TCE at 0, 1600, or 2400 ppm, 6 h/day for 20 days (n=8/group) and began learning the SDT 3 weeks later. Rats earned food by pressing one retractable response lever in a signal trial and a second lever in a blank (no signal) trial. TCE did not affect acquisition of the response rule or performance of the SDT after the intertrial interval (ITI) was changed from a constant value to a variable one. Increasing the trial presentation rate reduced accuracy equivalently in all groups. Injections of ethanol (0, 0.5, 1.0, 1.5 g/kg ip) and d-amphetamine (0, 0.1, 0.3, 1.0 mg/kg sc) systematically impaired performance as functions of drug dose. d-Amphetamine (1.0 mg/kg) reduced P(hit) more in the 2400-ppm TCE group than in the other groups. All rats required remedial training to learn a reversal of the response contingencies, which TCE did not interfere with. Thus, a history of exposure to TCE did not significantly alter learning or sustained attention in the absence of drugs. Although ethanol did not differentially affect the TCE groups, the effect of d-amphetamine is consistent with solvent-induced changes in dopaminergic functions in the CNS. Calculations indicated power values of 0.5 to 0.8 to detect main effects of TCE for the three primary endpoints. PMID:15019957

  14. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    PubMed

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  15. Neonatal endotoxin exposure changes neuroendocrine, cardiovascular function and mortality during polymicrobial sepsis in adult rats.

    PubMed

    Saia, Rafael Simone; Oliveira-Pelegrin, Gabriela Ravanelli; da Silva, Maria Emília Nadaletto Bonifácio; Aguila, Fábio Alves; Antunes-Rodrigues, José; Rocha, Maria José Alves; Cárnio, Evelin Capellari

    2011-08-01

    Our aim was to investigate whether neonatal LPS challenge may improve hormonal, cardiovascular response and mortality, this being a beneficial adaptation when adult rats are submitted to polymicrobial sepsis by cecal ligation and puncture (CLP). Fourteen days after birth, pups received an intraperitoneal injection of lipopolysaccharide (LPS; 100μg/kg) or saline. After 8-12 weeks, they were submitted to CLP, decapitated 4, 6 or 24h after surgery and blood was collected for vasopressin (AVP), corticosterone and nitrate measurement, while AVP contents were measured in neurohypophysis, supra-optic (SON) and paraventricular (PVN) nuclei. Moreover, rats had their mean arterial pressure (MAP) and heart rate (HR) evaluated, and mortality and bacteremia were determined at 24h. Septic animals with neonatal LPS exposure had higher plasma AVP and corticosterone levels, and higher c-Fos expression in SON and PVN at 24h after surgery when compared to saline treated rats. The LPS pretreated group showed increased AVP content in SON and PVN at 6h, while we did not observe any change in neurohypophyseal AVP content. The nitrate levels were significantly reduced in plasma at 6 and 24h after surgery, and in both hypothalamic nuclei only at 6h. Septic animals with neonatal LPS exposure showed increase in MAP during the initial phase of sepsis, but HR was not different from the neonatal saline group. Furthermore, neonatally LPS exposed rats showed a significant decrease in mortality rate as well as in bacteremia. These data suggest that neonatal LPS challenge is able to promote beneficial effects on neuroendocrine and cardiovascular responses to polymicrobial sepsis in adulthood. PMID:21549159

  16. Species-specific ultrastructure of neuronal lipofuscin in hippocampus and neocortex of subhuman mammals and humans.

    PubMed

    Boellaard, J W; Schlote, W; Hofer, W

    2004-01-01

    Lipofuscin represents an integral part of neurons and glial cells in mammals and in submammalian species. It is a special lysosomal organelle, takes part of cellular metabolism, and is a structural expression of catabolic pathways. Species-specific differences of lipofuscin indicate metabolic differences of the relevant neurons. The authors have studied the ultrastructure of neuronal lipofuscin in the hippocampus and cerebral neocortex of dogs, horses, cows, elephants, rats, mice, apes, and humans to answer the question of species-specific differences of this organelle. Paraffin sections of formalin-fixed material were investigated by hematoxylin-eosin and PAS staining, by fluorescence microscopy for autofluorescence, with a laser scanning confocal microscope and by electron microscopy. In the animals studied and in humans the lipofuscin displayed, in addition to the general trilaminar substructure, species-specific appearances. No differences were found in the lipofuscin structure between neocortical and hippocampal neurons of the separate animal species. In contrast, in humans, neurons of the hippocampus showed a particular lipofuscin structure, not only different from the neocortical one, but also with differences between CA1 and CA3/4 sectors. Interestingly, in apes a transitional situation was found with slight differences between neocortical and hippocampal lipofuscin, especially in the rhesus monkey. This peculiarity was corroborated by the distribution of special pentilaminar linear structures in the lipofuscin pigment in all animals, only sparsely in the rhesus monkey and not in humans. The results indicate that lipofuscin ultrastructure of neocortical and hippocampal neurons is species specific and that lipofuscin in the human hippocampal neurons displays structures characteristic of man differing from the neocortical neuronal lipofuscin. The neuronal lipofuscin of apes, especially of the rhesus monkey displays structures in between humans and lower

  17. Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity

    PubMed Central

    Hall, S.; Hunt, M.; Simon, A.; Cunnington, L.G.; Carracedo, L.M.; Schofield, I.S.; Forsyth, R.; Traub, R.D.

    2015-01-01

    Slow spike and wave discharges (0.5–4 Hz) are a feature of many epilepsies. They are linked to pathology of the thalamocortical axis and a thalamic mechanism has been elegantly described. Here we present evidence for a separate generator in local circuits of associational areas of neocortex manifest from a background, sleep-associated delta rhythm in rat. Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the “wave” component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the “spike” component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3—switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics. PMID:26109655

  18. ONTOGENY OF ETHANOL INDUCED MOTOR IMPAIRMENT FOLLOWING ACUTE ETHANOL: ASSESSMENT VIA THE NEGATIVE GEOTAXIS REFLEX IN ADOLESCENT AND ADULT RATS

    PubMed Central

    Ramirez, Ruby Liane; Spear, Linda Patia

    2010-01-01

    Adolescent rats have been observed to be less sensitive than adults to a number of ethanol effects that may serve as feedback cues to reduce further ethanol intake. Among these findings are a few reports of attenuated sensitivities of adolescents to ethanol-induced motor impairment. The purpose of the present study was to further explore potential age-related differences in ethanol-induced motor impairment in both male and female adolescent (postnatal day [P]28–32), and adult (P68-72) Sprague-Dawley rats using an inclined plane assessment of the negative geotaxis reflex. Adult males displayed significant motor impairment at 1.5 g/kg, whereas adolescent males required higher doses, showing significant motor impairment only at doses of 2.25 g/kg ethanol or greater. Intoxicated practice did not significantly influence level of motor impairment at either age. When female rats of both ages were separately analyzed in terms of their response to ethanol, a dose of 1.5 g/kg ethanol was found to significantly impair adults, whereas adolescent females showed significant motor impairment when challenged with 2.25 g/kg but not 1.5 g/kg ethanol. Yet when the 1.5 g/kg data of females at the two ages were directly compared, no significant age difference was seen at this dose. These data document an attenuated sensitivity of adolescent relative to adult rats to the motor impairing effects of ethanol using a stationary inclined plane test, an effect particularly robust in male animals, and demonstrates the utility of this test for assessment of motor coordination in adolescent and adult rats. PMID:20138187

  19. Parenteral magnesium load testing with /sup 28/Mg in weanling and young adult rats

    SciTech Connect

    Caddell, J.L.; Calhoun, N.R.; Howard, M.P.; Patterson, K.Y.; Smith, J.C. Jr.

    1981-06-01

    A sound diagnostic test for Mg deficiency is needed. This is a report of the parenteral Mg load test conducted in weanling and young adult rats fed a purified basal diet containing 3 mg magnesium/100 g with 150 mg of added magnesium/100 g (control) or 0 added magnesium (deficient). Weanlings were studied at about 1 week of dietary treatment and young adults at 2 weeks. The protocol included: a) a 6-hour preload urinary collection; b) an intraperitoneal load of 15 mg of magnesium/kg (weanlings) or 12 mg/kg (young adults) with 2 microCi 28Mg given simultaneously with each load; c) a 6-hour postload urinary collection; d) chemical analysis of selected tissues and urine for Mg; and e) 28Mg counting 6 and 24 hours postload. Controls all excreted large amounts of Mg pre- and postload, retaining less than 26% of nonradioactive loads. They had high urinary 28Mg counts. In Mg-deficient animals, the concentration of Mg in bone more than halved. These animals avidly conserved Mg and retained over 85% of nonradioactive Mg loads. Their 28Mg activity in vital organs was 3--6 times greater than in controls. We concluded that the parenteral Mg load test reliably identifies severe Mg deficiency.

  20. Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

    PubMed

    Dorce, Ana Leticia Coronado; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2010-01-01

    The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner. PMID:19945531

  1. An ultrastructural study of the phagocytic activity of astrocytes in adult rat brain.

    PubMed Central

    al-Ali, S Y; al-Hussain, S M

    1996-01-01

    The role of adult astrocytes in the removal of cell debris and foreign particles following injury to the brain is controversial. This study was undertaken to elucidate the response of adult astrocytes to needle injury of the rat cerebral cortex, using a suspension of colloidal carbon as a marker for phagocytosis. Either a single or 2 successive injections of colloidal carbon suspension were made into the cerebral cortex. The animals were allowed to survive for periods of from 1 to 30 d. Unequivocal involvement of astrocytes in the removal of carbon particles was evident only in those brains which had been subjected to 2 successive injections of carbon. The particles were located in membrane-bound vacuoles and were subsequently sequestered in lysosomes. Carbon-containing astrocytes were observed in the immediate vicinity of the lesion, in the adjacent parenchyma, around blood vessels and abutting carbon-containing macrophages. This study demonstrates that adult astrocytes are involved in phagocytosis, but only as a second line of defence. The possible significance of carbon-laden astrocytes further away from the site of the lesion is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8621323

  2. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring. PMID:26224008

  3. Cocaine Sensitization Increases Kyphosis and Modulates Neural Activity in Adult Nulliparous Rats

    PubMed Central

    Nephew, Benjamin C.; Caffrey, Martha K.; Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

    Although data from both animals and humans suggests that adult cocaine use can have long term effects on behavior, it is unknown if prior cocaine use affects future maternal behavior in nulliparous females. In the current study, cocaine or saline was administered to adult female rats for 10 days, the animals were withdrawn from cocaine for 7 days, and the females were then exposed to donor pups to induce the expression of maternal behavior. Nulliparous females sensitized to cocaine were more likely to retrieve pups, spent more time caring for the pups, and were more likely to express full maternal behavior on day 8 of pup exposure. The fMRI data revealed significant effects of pup exposure in the hippocampal CA1 region, and effects of cocaine in the anterior thalamus and periaqueductal gray. Prior adult cocaine use may have lasting effects on offspring care, and this effect is not dependent on pup mediated effects or the endocrine changes of gestation and lactation. The present findings provide support for the hypothesis that maternal motivation to exhibit maternal behavior is enhanced by prior cocaine sensitization, possibly due to cross sensitization between cocaine and the natural reward of maternal behavior. PMID:24371520

  4. Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs

    PubMed Central

    Miyanohara, Atsushi; Kamizato, Kota; Juhas, Stefan; Juhasova, Jana; Navarro, Michael; Marsala, Silvia; Lukacova, Nada; Hruska-Plochan, Marian; Curtis, Erik; Gabel, Brandon; Ciacci, Joseph; Ahrens, Eric T; Kaspar, Brian K; Cleveland, Don; Marsala, Martin

    2016-01-01

    Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients. PMID:27462649

  5. Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.

    PubMed

    Miyanohara, Atsushi; Kamizato, Kota; Juhas, Stefan; Juhasova, Jana; Navarro, Michael; Marsala, Silvia; Lukacova, Nada; Hruska-Plochan, Marian; Curtis, Erik; Gabel, Brandon; Ciacci, Joseph; Ahrens, Eric T; Kaspar, Brian K; Cleveland, Don; Marsala, Martin

    2016-01-01

    Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients. PMID:27462649

  6. Pattern separation, completion, and categorisation in the hippocampus and neocortex.

    PubMed

    Rolls, Edmund T

    2016-03-01

    The mechanisms for pattern completion and pattern separation are described in the context of a theory of hippocampal function in which the hippocampal CA3 system operates as a single attractor or autoassociation network to enable rapid, one-trial, associations between any spatial location (place in rodents, or spatial view in primates) and an object or reward, and to provide for completion of the whole memory during recall from any part. The factors important in the pattern completion in CA3 and also a large number of independent memories stored in CA3 include: a sparse distributed representation, representations that are independent due to the randomizing effect of the mossy fibres, heterosynaptic long-term depression as well as long-term potentiation in the recurrent collateral synapses, and diluted connectivity to minimize the number of multiple synapses between any pair of CA3 neurons which otherwise distort the basins of attraction. Recall of information from CA3 is implemented by the entorhinal cortex perforant path synapses to CA3 cells, which in acting as a pattern associator allow some pattern generalization. Pattern separation is performed in the dentate granule cells using competitive learning to convert grid-like entorhinal cortex firing to place-like fields, and in the dentate to CA3 connections that have diluted connectivity. Recall to the neocortex is achieved by a reverse hierarchical series of pattern association networks implemented by the hippocampo-cortical backprojections, each one of which performs some pattern generalization, to retrieve a complete pattern of cortical firing in higher-order cortical areas. New results on competitive networks show which factors contribute to their ability to perform pattern separation, pattern clustering, and pattern categorisation, and how these apply in different hippocampal and neocortical systems. PMID:26190832

  7. Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats.

    PubMed

    Iwamoto, J; Takeda, T; Katsumata, T; Tanaka, T; Ichimura, S; Toyama, Y

    2002-02-01

    The purpose of the present study was to determine whether etidronate treatment could prevent bone loss caused by orchidectomy (ORX) and unilateral sciatic neurectomy (NX) in adult male rats. Seventy-four male Wistar rats, aged 10 months, were randomly divided into eight groups: baseline controls (n = 10); age-matched sham-operated controls (AMC; n = 9); ORX (n = 9); NX (n = 10); ORX + NX (n = 9); ORX + etidronate treatment (ORX + E; n = 7); NX + E (n = 10); and ORX + NX + E (n = 10). Etidronate treatment (10 mg/kg per day subcutaneously) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, bone mineral density (BMD) of the proximal and middle tibia (PT and MT, respectively), distal and middle femur (DF and MF, respectively), and fourth lumbar vertebral body (LVB) was measured by dual-energy X-ray absorptiometry (Model DCS-600, Aloka, Tokyo, Japan). The mechanical properties of the MF and third LVB were measured by three-point bending and compression tests, respectively. Levels of urinary deoxypyridinoline (Dpd) and serum osteocalcin (Oc) were also measured by enzyme-linked immunosorbent assay. Four weeks of aging had no significant effects on BMD, bone mechanical properties, or bone markers. ORX significantly increased the levels of urinary Dpd and serum Oc, which resulted in significant decreases in BMD of the PT, MT, DF, MF, and fourth LVB, as well as the mechanical strength (maximum load) of the MF and third LVB. NX significantly increased levels of urinary Dpd and decreased levels of serum Oc, resulting in a significant decrease in BMD of the PT, DF, and fourth LVB. The ORX-induced decrease in BMD of the PT was more pronounced when combined with NX. Etidronate treatment for NX, ORX, and ORX + NX rats significantly decreased levels of urinary Dpd and serum Oc, resulting in complete prevention of loss of BMD and/or bone mechanical strength. The present study demonstrates the efficacy of etidronate treatment for prevention

  8. Posttraumatic seizures and epilepsy in adult rats after controlled cortical impact.

    PubMed

    Kelly, Kevin M; Miller, Eric R; Lepsveridze, Eka; Kharlamov, Elena A; Mchedlishvili, Zakaria

    2015-11-01

    Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. Provoked class 3-5 seizures were recorded by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI of the right parietal cortex; none of the 7 animals demonstrated subsequent spontaneous convulsive seizures. Monitoring with video and/or video-EEG was performed on 128 animals at various time points 8-619 days beyond one week following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in 7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually characterized by an initial change in behavior (head raising or animal alerting) followed by motor arrest during an ictal discharge that consisted of high-amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz class 3-5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI-injured, 13 controls) underwent transcardial perfusion for gross and microscopic studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure-function relationships that underlie epileptogenesis and PTE. PMID

  9. Extensor motoneurone properties are altered immediately before and during fictive locomotion in the adult decerebrate rat

    PubMed Central

    MacDonell, C W; Power, K E; Chopek, J W; Gardiner, K R; Gardiner, P F

    2015-01-01

    Key points This is the first report, in adult decerebrate rats, to examine intracellular hindlimb motoneurone properties during quiescence, fictive locomotion and a tonic period immediately before fictive locomotion that is characterized by increased peripheral nerve activity. It is shown for the first time during fictive locomotion that motoneurones become more responsive in the tonic period, suggesting that the motoneurone pool becomes primed before patterned motor output commences. Spike frequency adaptation exists in quiescence and during fictive locomotion during constant excitation with injected current but not during centrally driven fictive locomotion. Motoneurones within the extensor motor pool show changes in excitability even when they are not directly involved in locomotion. The data show increased responsiveness of motoneurones during locomotion via a lowered threshold for spike initiation and decreased rheobase. Abstract This study examined motoneurone properties during fictive locomotion in the adult rat for the first time. Fictive locomotion was induced via electrical stimulation of the mesencephalic locomotor region in decerebrate adult rats under neuromuscular blockade to compare basic and rhythmic motoneurone properties in antidromically identified extensor motoneurones during: (1) quiescence, before and after fictive locomotion; (2) the ‘tonic’ period immediately preceding locomotor-like activity, whereby the amplitude of peripheral flexor (peroneal) and extensor (tibial) nerves are increased but alternation has not yet occurred; and (3) locomotor-like episodes. Locomotion was identified by alternating flexor–extensor nerve activity, where the motoneurone either produced membrane oscillations consistent with a locomotor drive potential (LDP) or did not display membrane oscillation during alternating nerve activity. Cells producing LDPs were referred to as such, while those that did not were referred to as ‘idle’ motoneurones. LDP and

  10. PRENATAL COCAINE ELIMINATES THE SEX-DEPENDENT DIFFERENCES IN ACTIVATION OBSERVED IN ADULT RATS AFTER COCAINE CHALLENGE

    EPA Science Inventory

    In the adult rat, acute administration of cocaine results in enhanced expression of certain behaviors. his activation is often referred to as "stereotypy" because of its repetitive nature. epeated exposure to the same dose of cocaine does not result in tolerance or a diminution o...

  11. PULMONARY FUNCTION IN JUVENILE AND YOUNG ADULT RATS EXPOSED TO LOW-LEVEL NO2 WITH DIURNAL SPIKES

    EPA Science Inventory

    Pulmonary function was examined in juvenile and young adult Fischer-344 rats continuously exposed to NO2 (0.5, 1.0 or 2.0 ppm) for up to 6 weeks with twice daily 1 hr spikes equal to 3X the baseline concentration. The spike to baseline ratio was chosen to simulate morning and eve...

  12. EFFECTS OF SUBCHRONIC INHALATION OF LOW CONCENTRATIONS OF NITROGEN DIOXIDE. 1. THE PROXIMAL ALVEOLAR REGION OF JUVENILE AND ADULT RATS

    EPA Science Inventory

    Techniques were devised to isolate tissue from the epithelium of terminal airways and the alveoli proximal to the airways. One day old juveniles and six week old adult rats were exposed to either room air or 0.5 ppm NO2 for 23 hrs per day seven days per week. An additional group ...

  13. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  14. TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

    EPA Science Inventory

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

  15. ALKYLTIN INHIBITION OF ATPASE ACTIVITIES IN TISSUE HOMOGENATES AND SUBCELLULAR FRACTIONS FROM ADULT AND NEONATAL RATS (JOURNAL VERSION)

    EPA Science Inventory

    Inhibition of ATPase activities by triethyltin (TET), diethyltin (DET), monoethyltin (MET) and trimethyltin (TMT) was studied in homogenates of brain and liver from adult rats. MET did not produce significant inhibition. ATPase activities in brain and liver homogenates from TET-t...

  16. Effects of 6-hydroxydopamine lesioning of the medial prefrontal cortex on social interactions in adolescent and adult rats.

    PubMed

    Li, Chun-Rong; Huang, Guang-Biao; Sui, Zhi Yan; Han, Eui-Hyeog; Chung, Young-Chul

    2010-07-30

    Bilateral depletion of dopamine (DA) in the medial prefrontal cortex (mPFC) following local infusions of 6-hydroxydopamine (6-OHDA) was reported to affect mesolimbic DA neurotransmission and augment spontaneous and amphetamine-induced locomotion. However, the effects of 6-OHDA lesioning of the mPFC of adolescent rats have never been investigated. Given that dopaminergic neurons reach the peak of maturation during adolescence, we hypothesized that 6-OHDA lesioning of the mPFC during adolescence would have greater impact on subsequent behavioral parameters than would such lesioning during adulthood. The aim of this study was to investigate the effects of 6-OHDA lesioning of the mPFC on the open-field activities and novel investigative and socially interactive behaviors of adolescent and adult rats. Using a stereotaxic apparatus, 6-OHDA (8.0 microg) was injected bilaterally into the mPFC of adolescent and adult rats. After a 1-week recovery period, rats were placed in an open-field chamber, and spontaneous locomotion and other behaviors were monitored. Next, a novel toy was place in the center and behavioral responses were observed. One day later, socially interactive behaviors were measured by placing the lesioned rats into a cage with four unfamiliar rats matched for age. The tests of locomotor activity and novel investigative behaviors revealed no significant differences between the lesioned and sham groups of adolescent or adult rats. Grooming and socially interactive behaviors were significantly lower in the adolescent and adult lesioned groups than in each sham group. Interestingly, we observed more extensive impairment in socially interactive behaviors among the adolescent lesioned rats compared to the adult lesioned rats. The present study indicates that DA depletion in the mPFC causes significantly reduced grooming and socially interactive behaviors; this phenomenon may be comparable to the negative symptoms observed in schizophrenia. Further research is

  17. Abnormal secretion of reproductive hormones and antioxidant status involved in quinestrol-induced reproductive toxicity in adult male rat.

    PubMed

    Li, Jian; Wang, Hongwei; Zhang, Jiliang; Zhou, Bianhua; Si, Lifang; Wei, Lan; Li, Xiang

    2014-02-01

    This study aimed to evaluate the effects of quinestrol, a synthetic oestrogen homologue with reproductive toxicity, on the secretion of reproductive hormones and antioxidant status in adult male rat. Our results showed that quinestrol exposure significantly decreased the weight of the testis, epididymides, seminal vesicle, and prostate, as well as the sperm counts in the cauda epididymis of rats. Quinestrol significantly reduced the size of seminiferous tubules and the total number of spermatogenic cells. Serum testosterone, follitropin, and lutropin were also significantly reduced in a dose-related manner after quinestrol exposure. Meanwhile, the activity of superoxide dismutase, glutathione peroxidase, and total antioxide capacity significantly decreased, whereas the malondialdehyde and nitric oxide concentrations significantly increased in the testes. These findings revealed that endocrine disorders of reproductive hormones and oxidative stress may be involved in reproductive toxicity induced by quinestrol in adult male rats. PMID:24183492

  18. Perinatal undernutrition facilitates morphine sensitization and cross-sensitization to cocaine in adult rats: a behavioral and neurochemical study.

    PubMed

    Velazquez, E E; Valdomero, A; Orsingher, O A; Cuadra, G R

    2010-01-20

    The development of sensitization to the locomotor effects of morphine and cross-sensitization between morphine and cocaine were evaluated in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 30 days of age (D-rats), and compared with well-nourished animals (C-rats). Dose-response curves to morphine-induced locomotor activity (5, 7.5, 10 or 15 mg/kg, i.p., every other day for 5 days) revealed a shift to the left in D-rats compared to C-rats. This implies that D-rats showed behavioral sensitization to the lower dose of morphine used (5 mg/kg), which was ineffective in C-rats. Furthermore, when a cocaine challenge (10 mg/kg, i.p) was given 48 h after the last morphine administration, only D-rats exhibited cross-sensitization in morphine-pretreated animals (7.5 and 10 mg/kg). In order to correlate the differential response observed with the functioning of the mesocorticolimbic dopaminergic system, extracellular dopamine (DA) levels were measured in the nucleus accumbens (core and shell) and the dorsal caudate-putamen. A challenge with cocaine in morphine pre-exposed animals produced an increase in DA release, but only in the nucleus accumbens "core" of D-rats. Similar DA levels were found in the nucleus accumbens "shell" and in the dorsal caudate-putamen of both groups. Finally, these results demonstrate that D-rats had a lower threshold for developing both a progressive behavioral sensitization to morphine and a cross-sensitization to cocaine. In accordance with these behavioral findings, a higher responsiveness of the nucleus accumbens core, expressed by increased DA levels, both basal and after cocaine challenge, was observed in D-rats. PMID:19892003

  19. Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

    PubMed

    Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

    2012-12-01

    Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats. PMID:22832793

  20. Electroacupuncture upregulates ERK signaling pathways and promotes adult hippocampal neural progenitors proliferation in a rat model of depression

    PubMed Central

    2013-01-01

    Background In this study, we investigate the proliferation of adult neural stem cells (NSCs) in a chronic unpredictable stress (CUS) rat model of depression, the effects of electroacupunture (EA) on depressive-like symptoms and the corresponding signaling pathways. Methods SD rats were subjected to 4 weeks of CUS to induce depressive-like behaviors. EA was performed at the Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan) acupoints. Rats were injected with BrdU and the brains were cut into sections. Double-labeling with BrdU/Sox2 and p-ERK/Nestin was performed to demonstrate the in vivo proliferation of adult NSCs in hippocampus and ERK activation in NSCs. Hippocampal microdialysates of different groups were collected to observe the in vitro effects on NSCs. Results After 8 treatments, EA generated a clear antidepressant effect on the stressed rats and promoted the NSC proliferation. ERK activation might be involved in the antidepressant-like effects of EA treatment. Hippocampal microdialysates from EA-treated stressed rats influenced NSCs to form larger neural spheres and exhibit higher p-ERK level in vitro, compared to the untreated stressed rats. Meanwhile, the antidepressant-like effects of EA involved contribution from both acupoint specificity and electrical stimulus. Conclusions EA might interfere with the hippocampal microenvironment and enhance the activation of ERK signaling pathways. This could mediate, at least in part, the beneficial effects of EA on NSC proliferation and depressive-like behaviors. PMID:24165147

  1. Intermittent prenatal MDMA exposure alters physiological but not mood related parameters in adult rat offspring.

    PubMed

    Adori, Csaba; Zelena, Dóra; Tímár, Júlia; Gyarmati, Zsuzsa; Domokos, Agnes; Sobor, Melinda; Fürst, Zsuzsanna; Makara, Gábor; Bagdy, György

    2010-01-20

    The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior. PMID:19782105

  2. Comprehensive Analysis of Neonatal versus Adult Unilateral Decortication in a Mouse Model Using Behavioral, Neuroanatomical, and DNA Microarray Approaches

    PubMed Central

    Yoshikawa, Akira; Nakamachi, Tomoya; Shibato, Junko; Rakwal, Randeep; Shioda, Seiji

    2014-01-01

    Previously, studying the development, especially of corticospinal neurons, it was concluded that the main compensatory mechanism after unilateral brain injury in rat at the neonatal stage was due in part to non-lesioned ipsilateral corticospinal neurons that escaped selection by axonal elimination or neuronal apoptosis. However, previous results suggesting compensatory mechanism in neonate brain were not correlated with high functional recovery. Therefore, what is the difference among neonate and adult in the context of functional recovery and potential mechanism(s) therein? Here, we utilized a brain unilateral decortication mouse model and compared motor functional recovery mechanism post-neonatal brain hemisuction (NBH) with adult brain hemisuction (ABH). Three analyses were performed: (1) Quantitative behavioral analysis of forelimb movements using ladder walking test; (2) neuroanatomical retrograde tracing analysis of unlesioned side corticospinal neurons; and (3) differential global gene expressions profiling in unlesioned-side neocortex (rostral from bregma) in NBH and ABH on a 8 × 60 K mouse whole genome Agilent DNA chip. Behavioral data confirmed higher recovery ability in NBH over ABH is related to non-lesional frontal neocortex including rostral caudal forelimb area. A first inventory of differentially expressed genes genome-wide in the NBH and ABH mouse model is provided as a resource for the scientific community. PMID:25490135

  3. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one. PMID:25847268

  4. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

    SciTech Connect

    Krueger, Katharina Repges, Hendrik; Hippler, Joerg; Hartmann, Louise M.; Hirner, Alfred V.; Straub, Heidrun; Binding, Norbert; Musshoff, Ulrich

    2007-11-15

    In this study, the effects of pentavalent dimethylarsinic acid ((CH{sub 3}){sub 2}AsO(OH); DMA{sup V}) and trivalent dimethylarsinous acid ((CH{sub 3}){sub 2}As(OH); DMA{sup III}) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 {mu}mol/l. DMA{sup V} had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA{sup III} significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 {mu}mol/l DMA{sup III} in adult and 10 {mu}mol/l DMA{sup III} in young rats. Moreover, DMA{sup III} significantly affected the LTP-induction. Application of 10 {mu}mol/l DMA{sup III} resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA{sup III}. In slices of young rats, the depressant effects of DMA{sup III} were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA{sup V} on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential.

  5. A role for the prefrontal cortex in heroin-seeking after forced abstinence by adult male rats but not adolescents.

    PubMed

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-02-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. PMID:23072838

  6. A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

    PubMed Central

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-01-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir+ and Fos-ir− neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir+ neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. PMID:23072838

  7. Sex differences in anxiety-like behavior and locomotor activity following prenatal and postnatal methamphetamine exposure in adult rats.

    PubMed

    Hrubá, L; Schutová, B; Šlamberová, R

    2012-01-18

    The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behavior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure. PMID:21884713

  8. Preweaning cocaine exposure alters brain glucose metabolic rates following repeated amphetamine administration in the adult rat.

    PubMed

    Melnick, Susan M; Torres-Reveron, Annelyn; Dow-Edwards, Diana L

    2004-10-15

    Developmental cocaine exposure produces long-term alterations in function of many neuronal circuits. This study examined glucose metabolic rates following repeated amphetamine administration in adult male and female rats pretreated with cocaine during postnatal days (PND) 11-20. PND11-20 cocaine increased the response to amphetamine in many components of the motor system and the dorsal caudate-putamen, in particular, and decreased the metabolic response in the hypothalamus. While amphetamine alone produced widespread increases in metabolism, there were no cocaine-related effects in the mesolimbic, limbic or sensory structures. These data suggest that a brief cocaine exposure during development can alter ontogeny and result in abnormal neuronal responses to repeated psychostimulant administration in adulthood. PMID:15464226

  9. Neonatal stress from limited bedding elicits visceral hyperalgesia in adult rats.

    PubMed

    Guo, Yumei; Wang, Zhuo; Mayer, Emeran A; Holschneider, Daniel P

    2015-01-01

    Early life stress is a risk factor for developing functional pain disorders. The 'limited bedding' (LB) model elicits psychological stress in the dam and her pups by providing minimal nesting material following delivery. Little is known about the effects of LB on visceral pain. Rats (female, male) were exposed to LB on postnatal days 2-9. Electromyographic visceromotor responses were recorded at the age of 11-12 weeks during titrated colorectal distension. LB exposure resulted in significant visceral hyperalgesia in both sexes. Sex differences were demonstrated only in nonstressed controls, with females showing a greater visceromotor response. Our results prepare the way for use of the LB model in studying the development of visceral pain in adults with functional gastrointestinal disorders. PMID:25426824

  10. A Novel Model of Surgical Injury in Adult Rat Kidney: A “Pouch Model”

    PubMed Central

    Litbarg, Natalia O.; Vujicic, Snezana; Setty, Suman; Sethupathi, Periannan; Dunea, George; Arruda, Jose A.; Singh, Ashok K.

    2013-01-01

    Regenerative mechanisms after surgical injury have been studied in many organs but not in the kidney. Studying surgical injury may provide new insights into mechanisms of kidney regeneration. In rodent models, extrarenal tissues adhere to surgical kidney wound and interfere with healing. We hypothesized that this can be prevented by wrapping injured kidney in a plastic pouch. Adult rats tolerated 5/6 nephrectomy with pouch application well. Histological analysis demonstrates that application of the pouch effectively prevented formation of adhesions and induced characteristic wound healing manifested by formation of granulation tissue. Additionally, selected tubules of the wounded kidney extended into the granulation tissue forming branching tubular epithelial outgrowths (TEOs) without terminal differentiation. Tubular regeneration outside of renal parenchyma was not previously observed, and suggests previously unrecognized capacity for regeneration. Our model provides a novel approach to study kidney wound healing. PMID:24100472

  11. Acetylcholine determination of microdialysates of fetal neocortex grafts that induce recovery of learning.

    PubMed

    Miranda, M I; Bermúdez-Rattoni, F

    1998-03-01

    The microdialysis technique for acetylcholine (ACh) first became possible when sensitive and specific assays for ACh (pmol/sample range) were developed [G. Damsma, B.H.C. Westerink, P. de Boer, J.B. de Vries, A.S. Horn, Determination of basal acetylcholine release in freely moving rats by transstriatal dialysis coupled to on-line HPLC analysis: pharmacological aspects, Life Sci. 43 (1988) 1161-1168; G. Damsma, B.H.C. Westerink, A. Imperato, H. Rollema, J.B. de Vries, A. S. Horn, Automated brain dialysis of acetylcholine in freely moving rats: detection of basal acetylcholine, Life Sci. 41 (1987) 873-876; P.E. Potter, J.L. Meek, N.H. Neff, Acetylcholine and choline in neural tissue measured by HPLC with electrochemical detection, J. Neurochem. 41 (1983) 188-194; B.H.C. Westerink, G. Damsma, Determination of acetylcholine in microdialysates by HPLC and electrochemical detection, Neurosci. Protocols 20 (1993) 1-9.]. In the present protocol, the microdialysis technique was used to correlate ACh release with the recovery of the ability to acquire a conditioning taste aversion (CTA), by fetal brain grafts in insular cortex (IC) lesioned rats [M.I. Miranda, A.M. Lopez-Colome, F. Bermúdez Rattoni, Recovery of conditional taste aversion induced by fetal neocortex grafts. In vivo correlation of acetylcholine levels, Brain Res. 759 (1997) 141-148]. Three groups of IC lesioned rats showing disrupted CTA received cell suspension grafts of fetal tissue dissected from either the IC or occipital cortex (OC) of 16-day-old rat fetuses. One of the groups of IC-grafted animals was tested after 15 days post-graft; the other groups, IC- and OC-grafted animals, were tested after a recovery time of 45 days, as well as the groups of lesioned and unoperated animals used as control. After the CTA test, guide cannulas were stereotaxically implanted into the IC of all groups. Two days later, microdialysis was performed to determine the extracellular levels of ACh inside the graft. The

  12. Behavioral Differences Between Late Preweanling and Adult Female Sprague-Dawley Rat Exploration of Animate and Inanimate Stimuli and Food

    PubMed Central

    Smith, Kiersten S.; Morrell, Joan I.

    2010-01-01

    The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied stimuli, including inanimate objects systematically varied in size and interactive properties, biological stimuli, and food. Preweanlings were faster to initiate specific stimulus exploration and were more interactive with most specific stimuli than adults; the magnitude of these preweanling-adult quantitative differences ranged from fairly small to very large depending upon the stimulus. In contrast, preweanlings were adult-like in their interaction with food and prey. Preweanling response to some stimuli, for example to live pups, was qualitatively different from that of adults; the preweanling behavioral repertoire was characterized by pup-seeking while the adult response was characterized by pup-avoidance. The specific stimulus interactions of preweanlings were less impacted than those of adults by the time of day of testing and placement of a stimulus in an anxiety-provoking location. The impact of novelty was stimulus dependent. The differences in interactions of preweanlings versus adults with specific stimuli suggests that CNS systems underlying these behavior patterns are at different stages of immaturity at PND 18 such that there may be an array of developmental trajectories for various categories of specific stimuli. These data provide a basis for the use of the preweanling as a preclinical model for understanding and medicating human disorders during development that are characterized by dysfunctional interactions with specific stimuli. PMID:21056059

  13. Adolescent Intermittent Ethanol Exposure Is Associated with Increased Risky Choice and Decreased Dopaminergic and Cholinergic Neuron Markers in Adult Rats

    PubMed Central

    Boutros, Nathalie; Semenova, Svetlana; Liu, Wen; Crews, Fulton T.

    2015-01-01

    Background: Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats. Methods: Adolescent (postnatal day 28–53) rats were administered 5g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-days–on/2-days–off exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain. Results: All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice. Conclusions: The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences. PMID:25612895

  14. A family of transposable elements co-opted into developmental enhancers in the mouse neocortex

    PubMed Central

    Notwell, James H.; Chung, Tisha; Heavner, Whitney; Bejerano, Gill

    2015-01-01

    The neocortex is a mammalian-specific structure that is responsible for higher functions such as cognition, emotion, and perception. To gain insight into its evolution and the gene regulatory codes that pattern it, we studied the overlap of its active developmental enhancers with transposable element families and compared this overlap to uniformly shuffled enhancers. Here we show a striking enrichment of the MER130 repeat family among active enhancers in the mouse dorsal cerebral wall, which gives rise to the neocortex, at embryonic day 14.5 (E14.5). We show that MER130 instances preserve a common code of transcriptional regulatory logic, function as enhancers, and are adjacent to critical neocortical genes. MER130, a nonautonomous interspersed transposable element, originates in the tetrapod or possibly Sarcopterygii ancestor, which far predates the appearance of the neocortex. Our results show that MER130 elements were recruited, likely through their common regulatory logic, as neocortical enhancers. PMID:25806706

  15. A family of transposable elements co-opted into developmental enhancers in the mouse neocortex.

    PubMed

    Notwell, James H; Chung, Tisha; Heavner, Whitney; Bejerano, Gill

    2015-01-01

    The neocortex is a mammalian-specific structure that is responsible for higher functions such as cognition, emotion and perception. To gain insight into its evolution and the gene regulatory codes that pattern it, we studied the overlap of its active developmental enhancers with transposable element (TE) families and compared this overlap to uniformly shuffled enhancers. Here we show a striking enrichment of the MER130 repeat family among active enhancers in the mouse dorsal cerebral wall, which gives rise to the neocortex, at embryonic day 14.5. We show that MER130 instances preserve a common code of transcriptional regulatory logic, function as enhancers and are adjacent to critical neocortical genes. MER130, a nonautonomous interspersed TE, originates in the tetrapod or possibly Sarcopterygii ancestor, which far predates the appearance of the neocortex. Our results show that MER130 elements were recruited, likely through their common regulatory logic, as neocortical enhancers. PMID:25806706

  16. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats

    SciTech Connect

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-12-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 {mu}g/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor {beta} was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.

  17. Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats.

    PubMed

    Réus, Gislaine Z; Scaini, Giselli; Jeremias, Gabriela C; Furlanetto, Camila B; Morais, Meline O S; Mello-Santos, Lis Maira; Quevedo, João; Streck, Emilio L

    2014-10-01

    Methylphenidate (MPH) is commonly prescribed for children who have been diagnosed with attention deficit hyperactivity disorder (ADHD); however, the action mechanisms of methylphenidate have not been fully elucidated. Studies have shown a relationship between apoptosis signaling pathways and psychiatric disorders, as well as in therapeutic targets for such disorders. So, we investigated if chronic treatment with MPH at doses of 1, 2 and 10mg/kg could alter the levels of pro-apoptotic protein, Bax, anti-apoptotic protein, Bcl-2, caspase-3 and cytochrome c in the brain of young and adult Wistar rats. Our results showed that MPH at all doses increased Bax in the cortex; the Bcl-2 and caspase-3 were increased with MPH (1mg/kg) and were reduced with MPH (2 and 10mg/kg); the cytochrome c was reduced in the cortex after treatment with MPH at all doses; in the cerebellum there was an increase of Bax with MPH at all doses, however, there was a reduction of Bcl-2, caspase-3, and cytochrome c with MPH (2 and 10mg/kg); in the striatum the treatment with MPH (10mg/kg) decreased caspase-3 and cytochrome c; treatment with MPH (2 and 10mg/kg) increased Bax and decreased Bcl-2 in the hippocampus; and the caspase-3 and cytochrome c were reduced in the hippocampus with MPH (10mg/kg). In conclusion, our results suggest that MPH influences plasticity in the brain of young and adult rats; however, the effects were dependent of age and brain area, on the one hand activating the initial cascade of apoptosis, increasing Bax and reducing Bcl-2, but otherwise inhibiting apoptosis by reduction of caspase-3 and cytochrome c. PMID:25128604

  18. Sex Differences in Adult Cognitive Deficits after Adolescent Nicotine Exposure in Rats

    PubMed Central

    Pickens, Laura R. G.; Rowan, James D.; Bevins, Rick A.; Fountain, Stephen B.

    2013-01-01

    This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood. PMID:23673345

  19. Developmental Methoxychlor Exposure Affects Multiple Reproductive Parameters and Ovarian: Folliculogenesis and Gene Expression in Adult Rats

    PubMed Central

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-01-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 μg/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post-coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor β was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis. PMID:18848953

  20. Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

    PubMed

    Figueiredo, Mariana Sarto; da Conceição, Ellen Paula Santos; de Oliveira, Elaine; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar

    2015-10-14

    Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and adrenaline β2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11β-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11β-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during

  1. Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat.

    PubMed

    Cao, Qilin; Zhang, Yi Ping; Iannotti, Christopher; DeVries, William H; Xu, Xiao-Ming; Shields, Christopher B; Whittemore, Scott R

    2005-02-01

    A graded contusion spinal cord injury (SCI) was created in the adult rat spinal cord using the Infinite Horizons (IH) impactor to study the correlation between injury severity and anatomical, behavioral, and electrophysiological outcomes. Adult Fisher rats were equally divided into five groups and received contusion injuries at the ninth thoracic level (T9) with 100, 125, 150, 175, or 200 kdyn impact forces, respectively. Transcranial magnetic motor-evoked potentials (tcMMEPs) and BBB open-field locomotor analyses were performed weekly for 4 weeks postinjury. Our results demonstrated that hindlimb locomotor function decreased in accordance with an increase in injury severity. The locomotor deficits were proportional to the amount of damage to the ventral and lateral white matter (WM). Locomotor function was strongly correlated to the amount of spared WM, which contains the reticulospinal and propriospinal tracts. Normal tcMMEP latencies were recorded in control, all of 100-kdyn-injured and half of 125-kdyn-injured animals. Delayed latency responses were recorded in some of 125-kdyn-injured and all of 150-kdyn-injured animals. No tcMMEP responses were recorded in 175- and 200-kdyn-injured animals. Comparison of tcMMEP responses with areas of WM loss or demyelination identified the medial ventrolateral funiculus (VLF) as the location of the tcMMEP pathway. Immunohistochemical and electromicroscopic (EM) analyses showed the presence of demyelinated axons in WM tracts surrounding the lesion cavities at 28 days postinjury. These data support the notion that widespread WM damage in the ventral and lateral funiculi may be a major cause for locomotor deficits and lack of tcMMEP responses after SCI. PMID:15629760

  2. The turnover of myelin phospholipids in the adult and developing rat brain

    PubMed Central

    Jungalwala, F. B.; Dawson, R. M. C.

    1971-01-01

    1. Inorganic [32P]phosphate, [U-14C]glycerol and [2-14C]ethanolamine were injected into the lateral ventricles in the brains of adult rats, and the labelling of individual phospholipids was followed over 2–4 months in both a microsomal and a highly purified myelin fraction. 2. All the phospholipids in myelin became appreciably labelled, although initially the specific radioactivities of the microsomal phospholipids were somewhat higher. Eventually the specific radioactivities in microsomal and myelin phospholipids fell rapidly at a rate corresponding to the decline of radioactivity in the acid-soluble pools. 3. Equivalent experiments carried out in developing rats with [32P]phosphate administered at the start of myelination showed some persistence of phospholipid labelling in the myelin, but this could partly be attributed to the greater retention of 32P in the acid-soluble phosphorus pool and recycling. 4. It is concluded that a substantial part of the phospholipid molecules in adult myelin membranes is readily exchangeable, although a small pool of slowly exchangeable material also exists. 5. A slow incorporation into or loss of labelled precursor from myelin phospholipids does not necessarily give a good indication of the rate of renewal of the molecules in the membrane. As presumably such labelled molecules originate by exchange with those in another membrane site (not necessarily where synthesis occurs) it is only possible to calculate the turnover rate in the myelin membrane if the behaviour of the specific radioactivity with time of the phospholipid molecules in the immediate precursor pool is known. PMID:5124379

  3. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  4. Extensor motoneurone properties are altered immediately before and during fictive locomotion in the adult decerebrate rat.

    PubMed

    MacDonell, C W; Power, K E; Chopek, J W; Gardiner, K R; Gardiner, P F

    2015-05-15

    This study examined motoneurone properties during fictive locomotion in the adult rat for the first time. Fictive locomotion was induced via electrical stimulation of the mesencephalic locomotor region in decerebrate adult rats under neuromuscular blockade to compare basic and rhythmic motoneurone properties in antidromically identified extensor motoneurones during: (1) quiescence, before and after fictive locomotion; (2) the 'tonic' period immediately preceding locomotor-like activity, whereby the amplitude of peripheral flexor (peroneal) and extensor (tibial) nerves are increased but alternation has not yet occurred; and (3) locomotor-like episodes. Locomotion was identified by alternating flexor-extensor nerve activity, where the motoneurone either produced membrane oscillations consistent with a locomotor drive potential (LDP) or did not display membrane oscillation during alternating nerve activity. Cells producing LDPs were referred to as such, while those that did not were referred to as 'idle' motoneurones. LDP and idle motoneurones during locomotion had hyperpolarized spike threshold (Vth ; LDP: 3.8 mV; idle: 5.8 mV), decreased rheobase and an increased discharge rate (LDP: 64%; idle: 41%) during triangular ramp current injection even though the frequency-current slope was reduced by 70% and 55%, respectively. Modulation began in the tonic period immediately preceding locomotion, with a hyperpolarized Vth and reduced rheobase. Spike frequency adaptation did not occur in spiking LDPs or firing generated from sinusoidal current injection, but occurred during a sustained current pulse during locomotion. Input conductance showed no change. Results suggest motoneurone modulation occurs across the pool and is not restricted to motoneurones engaged in locomotion. PMID:25809835

  5. Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.

    PubMed Central

    Iñiguez, M A; Rodriguez-Peña, A; Ibarrola, N; Morreale de Escobar, G; Bernal, J

    1992-01-01

    The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain. Images PMID:1379612

  6. Hyparrhenia hirta: A potential protective agent against hematotoxicity and genotoxicity of sodium nitrate in adult rats.

    PubMed

    Bouaziz-Ketata, Hanen; Salah, Ghada Ben; Mahjoubi, Amira; Aidi, Zied; Kallel, Choumous; Kammoun, Hassen; Fakhfakh, Faiza; Zeghal, Najiba

    2015-11-01

    The present study was carried out to examine the adverse hematotoxic and genotoxic effects of water nitrate pollution on male adult rats and the use of hyparrhenia hirta methanolic extract in alleviating these effects. Sodium nitrate (NaNO3 ) was administered to adult rats by oral gavage at a dose of 400 mg kg(-1) bw daily for 50 days, while hyparrhenia hirta methanolic extract was given by drinking water at a dose of 1.5 mg mL(-1) (200 mg kg(-1) bw). The NaNO3 -treated group showed a significant decrease in red blood cell count, hemoglobin and hematocrit and a significant increase in total white blood cell, in neutrophil and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in treated groups compared to those of controls. Meanwhile, the results showed a marked reduction in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, along with an elevation in the level of lipid peroxidation and a reduction in the total glutathione content, indicating the induction of oxidative stress in the erythrocytes of NaNO3 -treated group. Interestingly, NaNO3 treatment showed a significant increase in the frequencies of total chromosomal aberrations, aberrant metaphases and micronucleus in bone-marrow cells. The oxidative stress induced by nitrate treatment might be the major cause for chromosomal rearrangements as free radicals leading to DNA damage. Hyparrhenia hirta methanolic extract appeared to be effective against hematotoxic and genotoxic changes induced by nitrate, as evidenced by the improvement of the markers cited above. PMID:24740966

  7. Inhibition of Adult Rat Retinal Ganglion Cells by D1-type Dopamine Receptor Activation

    PubMed Central

    Hayashida, Yuki; Rodríguez, Carolina Varela; Ogata, Genki; Partida, Gloria J.; Oi, Hanako; Stradleigh, Tyler W.; Lee, Sherwin C.; Colado, Anselmo Felipe; Ishida, Andrew T.

    2011-01-01

    The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D1a-receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D1-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats. These ligands curtailed repetitive spiking during constant current injections, and reduced the number and rate of rise of spikes elicited by fluctuating current injections without significantly altering the timing of the remaining spikes. Consistent with mediation by D1-type receptors, SCH-23390 reversed the effects of dopamine on spikes. Contrary to a recent report, spike inhibition by dopamine was not precluded by blocking Ih. Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na+ current (INa) amplitude and tetrodotoxin, at doses that reduced INa as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D1-type dopamine receptor activation can alter mammalian retinal ganglion cell excitability, and demonstrate that dopamine can modulate spikes in these cells by a mechanism different from the pre- and postsynaptic means proposed by previous studies. To our knowledge, our results also provide the first evidence that dopamine receptor activation can reduce excitability without altering the temporal precision of spike firing. PMID:19940196

  8. Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats.

    PubMed

    Ko, Meng-Chang; Hung, Yu-Hui; Ho, Pei-Yin; Yang, Yi-Ling; Lu, Kwok-Tung

    2014-12-01

    Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life. PMID:24945924

  9. Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers.

    PubMed

    He, Z P; Tan, W Q; Tang, Y F; Zhang, H J; Feng, M F

    2004-04-01

    Oval cells, putative hepatic stem cells, could potentially provide a novel solution to the severe shortage of donor livers, because of their ability to proliferate and differentiate into functional hepatocytes. We have previously demonstrated that oval cells can be induced to differentiate into cells with morphologic, phenotypic, and functional characteristics of mature hepatocytes. In this study, we have established a new model combining ethionine treatment with partial hepatectomy to activate oval cells, then developed a procedure utilizing selective enzymatic digestion and density gradient centrifugation to isolate and purify such cells from heterogeneous liver cell population. We identified oval cells by their morphological characteristics and phenotypic properties, thereby providing definitive evidence of the presence of hepatic stem-like cells in adult rat livers. Viewed by transmission electron microscopy, they were small cells with ovoid nuclei, a high nucleus/cytoplasm ratio and few organelles, including mitochondria and endoplasmic reticulum. Flow cytometric assay showed that these cells highly expressed OV-6, cytokeratin-19 (CK-19) and albumin. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis displayed that the freshly isolated cells co-expressed albumin, cytokeratin-7 (CK-7) and CK-19 mRNA, indicating that they were essentially bipotential hepatic stem-like cells. Furthermore, we set up a culture system containing growth factors and a fibroblast feeder layer, to provide nourishment to these cells. Thus, we were able to culture them in vitro for more than 3 months, with the number of cells doubling 100 times. Gene expressions of albumin, CK-7 and CK-19 in the cells derived from the expanding colonies at day 95 were confirmed by RT-PCR analysis. These data suggested that the hepatic oval cells derived from adult rat livers possess a high potential to proliferate in vitro with a large increase in number, while maintaining the bipotential

  10. Effect of ethanol in utero on higher nervous activity and protein and lipid metabolism in the rat brain

    SciTech Connect

    Zabbudovskii, A.L.; Zhulin, V.V.

    1985-10-01

    The authors study parameters of protein phosphorylation and glycoprotein and phospholipid synthesis in the neocortex and hippocampus of adult rats and compare the findings with the results of an investigation of formation and preservation of defensive conditioned reflexes. The pattern of changes in these metabolic parameters are studied in response to stress. For the biochemical tests, the animals were lightly anesthetized with ether and injected with a mixture of (P 32)-orthophosphate and (H 3)-fucose. Phospholipids were identified with molybdate reagent and radioactivity of the protein digest and lipids was measured in Bray's scintillator. The study shows that the use of stress brought metabolic differences between the brain of the experimental and control rats more clearly to light.

  11. Prenatal stress induces vulnerability to nicotine addiction and alters D2 receptors' expression in the nucleus accumbens in adult rats.

    PubMed

    Said, N; Lakehayli, S; El Khachibi, M; El Ouahli, M; Nadifi, S; Hakkou, F; Tazi, A

    2015-09-24

    Prenatal stress (PS) can induce several long-lasting behavioral and molecular abnormalities in rats. It can also be considered as a risk factor for many psychiatric diseases like schizophrenia, depression or PTSD and predispose to addiction. In this study, we investigated the effect of prenatal stress on the reinforcing properties of nicotine in the CPP paradigm. Then, we examined the mRNA expression of the D2 dopaminergic receptors using the quantitative real-time PCR technique in the nucleus accumbens (NAcc). We found that prenatally stressed rats exhibited a greater place preference for the nicotine-paired compartment than the control rats. Moreover, we observed an overexpression of the DRD2 gene in adult offspring stressed in utero and a downregulation in the PS NIC group (PS rats treated with nicotine) compared with their control counterparts (C NIC). These data suggest that maternal stress can permanently alter the offspring's addictive behavior and D2 receptors' expression. PMID:26192093

  12. Calcium antagonist flunarizine hydrochloride affects striatal D2 dopamine receptors in the young adult and aged rat brain.

    PubMed

    Asanuma, M; Ogawa, N; Haba, K; Hirata, H; Mori, A

    1991-01-01

    The calcium (Ca) antagonist flunarizine hydrochloride (FNZ) has been reported to induce parkinsonism, especially in the elderly. The effects of FNZ on dopamine receptors in rat striatal membranes, especially in aged rats, were studied using radiolabeled receptor assay. Similar displacing potencies in [(3)H]spiperone bindings were exhibited for FNZ and the Ca antagonists verapamil and nicardipine. FNZ was found to directly and competitively effect D2 receptors (D2-Rs) as an antagonist, without effecting D1 receptors. Furthermore, the washing of preoccupied membranes revealed that FNZ has a long-acting potent effect on D2-Rs. The comparative study of FNZ and sulpiride in young-adult and aged rats showed that the effect of FNZ on D2-Rs was more marked in aged rats. These results might be related to FNZ-induced parkinsonism and its high incidence in the elderly. PMID:15374420

  13. Fenugreek potent activity against nitrate-induced diabetes in young and adult male rats.

    PubMed

    El-Wakf, Azza M; Hassan, Hanaa A; Mahmoud, Ashraf Z; Habza, Marwa N

    2015-05-01

    Nitrate has described as an endocrine disruptor that promotes onset of diabetes. This study was undertaken to evaluate diabetic effect of high nitrate intake in young and adult male rats and its amelioration by fenugreek administration. The study revealed significant increase in serum glucose and blood glycosylated hemoglobin (HbA1c%), while serum insulin and liver glycogen were decreased among nitrate exposed animals, in particular the young group. A significant reduction in the body weight gain and serum thyroid hormones (T4 & T3) was also recorded. Further reduction in serum levels of urea and creatinine, as well as total protein in serum, liver and pancreas was demonstrated, with elevation in their levels in the urine of all nitrate exposed groups. Meanwhile, the activity of serum transaminases (ALT and AST) was increased, with decline in their activity in the liver tissue. In addition, an elevation in serum total bilirubin, tissues (liver and pancreas) nitric oxide and lipid profile, as well as liver activity of glucose-6-phosphatase was recorded. Fenugreek administration to nitrate exposed rats was found to be effective in alleviating hyperglycemia and other biochemical changes characterizing nitrate-induced diabetes. So, fenugreek can be considered to possess potent activity against onset of nitrate induced-diabetes. PMID:24615531

  14. Anterograde labeling of ventrolateral funiculus pathways with spinal enlargement connections in the adult rat spinal cord

    PubMed Central

    Reed, William R.; Shum-Siu, Alice; Whelan, Ashley; Onifer, Stephen M.; Magnuson, David S.K.

    2009-01-01

    The ventrolateral funiculus in the spinal cord has been identified as containing important ascending and descending pathways related to locomotion and interlimb coordination. The purpose of this descriptive study was to investigate the patterns of axon termination of long ascending and descending ventrolateral pathways within the cervical and lumbar enlargements of the adult rat spinal cord. To accomplish this, we made discrete unilateral injections of the tracer biotinylated dextran-amine (BDA) into the ventrolateral white matter at T9. Although some BDA-labeled axons with varicosities were found bilaterally at all cervical levels, particularly dense BDA-labeling was observed in laminae VIII and IX ipsilaterally at the C6 and C8 levels. In the same animals, dense terminal labeling was found in the lumbar enlargement in medial lamina VII and ventromedial laminae VIII and IX contralaterally. This labeling was most apparent in the more rostral lumbar segments. These observations continue the characterization of inter-enlargement (long propriospinal) pathways, illustrating a substantial and largely reciprocal inter-enlargement network with large numbers of both ascending and descending ventrolateral commissural neurons. These pathways are anatomically well-suited to the task of interlimb coordination and to participate in the remarkable recovery of locomotor function seen in the rat following thoracic spinal cord injuries that spare as little as 20% of the total white matter cross sectional area. PMID:19766612

  15. Metabolic alterations in liver and testes of adult and newborn rats following cadmium administration

    SciTech Connect

    Agarwal, A.K.

    1988-04-01

    A large number of studies have been conducted to understand the effect of cadmium on cellular intermediary metabolism. Although, most of the metal is stored in liver and kidney, the organ affected most in acute toxicity is testis. Increased lipid peroxidation and decreased mitochondrial respiration along with other cellular enzyme activities have been reported to take place due to cadmium administration. The present experiment was designed to study the effect of acute cadmium administration on the activities of some of the tissue enzyme systems that provide the reducing equivalent NADPH. The levels of NADH and NADPH were also measured. All the measurements were conducted in two tissues: liver and testes. The effect of simultaneous administration of zinc on cadmium induced changes was also determined. Newborn animals have been found to be resistant to many effects of cadmium. The present studies were also conducted in newborn rat liver and testes. The purpose of the study is to compare the effects of cadmium on adult and new born rats.

  16. Neurobehavioral assessment following e-cigarette refill liquid exposure in adult rats.

    PubMed

    Golli, Narges El; Dallagi, Yosra; Rahali, Dalila; Rejeb, Ines; Fazaa, Saloua El

    2016-07-01

    The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28 μl/kg of body weight of e-liquid with/without a dose of 0.5 mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short-term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela's inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out. PMID:27401341

  17. Lack of Reproductive Toxicity in Adult Male Rats Exposed to Interferon-Alpha.

    PubMed

    Rosa, Josiane de Lima; Cavariani, Marilia Martins; Borges, Cibele dos Santos; Leite, Gabriel Adan Araújo; Anselmo-Franci, Janete Aparecida; Kempinas, Wilma De Grava

    2015-01-01

    Interferon-alpha (IFN- α), a type I IFN, is a protein with antiviral, antiproliferative, and immunoregulatory activities, widely used in the treatment of several types of cancers as well as hepatitis B and C. Decrease of libido and erectile dysfunction are commonly reported by male patients during treatment of chronic hepatitis C with IFN- α . However, IFN therapy-associated underlying factors attributed to sexual dysfunction are still not well defined. Currently, there are few studies investigating the effects of IFN on male reproductive system functions. Given that, the aim of the present investigation was to examine effects of subchronic exposure to IFN- α (5 × 10(4) U/kg and 10 × 10(4) U/kg, 30 d) on serum hormones, sperm parameters, fertility, and testicular and epididymal hystopathology and morphometry in adult male Wistar rats. None of the evaluated parameters was markedly altered by IFN- α . Thus, our results suggest that exposure to IFN- α , in this experimental design, did not adversely affect sperm quality and fertile capacity of male rats. PMID:26488366

  18. Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats

    PubMed Central

    Li, Sheng-Guang; Wang, Jin-Yan; Luo, Fei

    2012-01-01

    Background Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent pain-related behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. Methodology/Principal Findings In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. Conclusions/Significance These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight the importance of treatment of chronic pain at an early stage. PMID:22574223

  19. Efficient estimation of the total number of acini in adult rat lung

    PubMed Central

    Barré, Sébastien F.; Haberthür, David; Stampanoni, Marco; Schittny, Johannes C.

    2014-01-01

    Abstract Pulmonary airways are subdivided into conducting and gas‐exchanging airways. An acinus is defined as the small tree of gas‐exchanging airways, which is fed by the most distal purely conducting airway. Until now a dissector of five consecutive sections or airway casts were used to count acini. We developed a faster method to estimate the number of acini in young adult rats. Right middle lung lobes were critical point dried or paraffin embedded after heavy metal staining and imaged by X‐ray micro‐CT or synchrotron radiation‐based X‐rays tomographic microscopy. The entrances of the acini were counted in three‐dimensional (3D) stacks of images by scrolling through them and using morphological criteria (airway wall thickness and appearance of alveoli). Segmentation stopper were placed at the acinar entrances for 3D visualizations of the conducting airways. We observed that acinar airways start at various generations and that one transitional bronchiole may serve more than one acinus. A mean of 5612 (±547) acini per lung and a mean airspace volume of 0.907 (±0.108) μL per acinus were estimated. In 60‐day‐old rats neither the number of acini nor the mean acinar volume did correlate with the body weight or the lung volume. PMID:24997068

  20. Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study.

    PubMed

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Jurijević, Branka Šošić; Balind, Snežana Raus; Brajković, Gordana; Perčinić-Popovska, Florina; Milošević, Verica

    2016-05-01

    Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically. Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats. Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary. PMID:27017477

  1. Constraint-induced movement therapy enhanced neurogenesis and behavioral recovery after stroke in adult rats.

    PubMed

    Zhao, Chuansheng; Wang, Jun; Zhao, Shanshan; Nie, Yingxue

    2009-08-01

    Constraint-induced movement therapy (CIMT) has been extensively used for stroke rehabilitation. CIMT encourages use of the impaired limb along with restraint of the ipsilesional limb in daily life, and may promote behavioral recovery and induce structural changes in brain after stroke. The aim of this study was to investigate whether CIMT enhances neurogenesis in rat brain after stroke that was generated by middle cerebral artery occlusion. Adult rats were divided into sham group, ischemia group and ischemia treated with CIMT group. Rats of CIMT group were treated with a plaster cast to restrain the healthy forelimb for 14 days beginning 1 week after ischemia. The proliferation of neuronal cells labeled with bromodeoxyuridine (BrdU) and behavioral recovery were analyzed at day 29 after ischemia. We also measured the tissue level of stromal cell-derived factor 1 (SDF-1) by ELISA. SDF-1 might be involved in the regulation of neurogenesis following stroke. In the subventricular zone of the animals treated with CIMT, there was a significant increase in the number of BrdU-positive cells (135 +/- 18, P < 0.05), compared with ischemia group (87 +/- 12) or sham group (18 +/- 3.6). Likewise, in the dentate gyrus, animals treated with CIMT showed a significant increase in BrdU-positive cells (296 +/- 26, P < 0.05) compared with ischemia group (225 +/- 18) or sham group (162 +/- 11). CIMT treatment after stroke significantly improved behavioral performances and increased the SDF-1 protein levels in the cortex and dentate gyrus. In conclusion, CIMT treatment enhances neurogenesis and functional recovery after stroke. PMID:19638734

  2. Adrenal steroidogenesis disruption caused by HDL/cholesterol suppression in diethylstilbestrol-treated adult male rat.

    PubMed

    Haeno, Satoko; Maeda, Naoyuki; Yamaguchi, Kousuke; Sato, Michiko; Uto, Aika; Yokota, Hiroshi

    2016-04-01

    The synthetic estrogen diethylstilbestrol is used to prevent miscarriages and as a therapeutic treatment for prostate cancer, but it has been reported to have adverse effects on endocrine homeostasis. However, the toxicity mechanism is poorly understood. Recently, we reported that diethylstilbestrol impairs adrenal steroidogenesis via cholesterol insufficiency in adult male rats. In the present study, we found that the adrenal cholesterol level was significantly reduced without of the decrease in other precursors in the adrenal steroidogenesis 24 h after a single dose of diethylstilbestrol (0.33 μg/g body mass). The serum HDL/cholesterol level was also reduced only 12 h after the diethylstilbestrol exposure. The level of Apo E, which is indispensable for HDL/cholesterol maturation, was decreased in both the HDL and VLDL/LDL fractions, whereas the level of Apo A1, which is an essential constituent of HDL, was not altered in the HDL fraction. Because the liver is a major source of Apo E and Apo A1, the secretion rates of these proteins were examined using a liver perfusion experiment. The secretion rate of Apo A1 from the liver was consistent between DES-treated and control rats, but that of Apo E was comparatively suppressed in the DES-treated rats. The disruption of adrenal steroidogenesis by diethylstilbestrol was caused by a decrease in serum HDL/cholesterol, which is the main source of adrenal steroidogenesis, due to the inhibition of Apo E secretion from the liver. PMID:26349937

  3. Map transfer from the thalamus to the neocortex: inputs from the barrel field.

    PubMed

    Lokmane, Ludmilla; Garel, Sonia

    2014-11-01

    Sensory perception relies on the formation of stereotyped maps inside the brain. This feature is particularly well illustrated in the mammalian neocortex, which is subdivided into distinct cortical sensory areas that comprise topological maps, such as the somatosensory homunculus in humans or the barrel field of the large whiskers in rodents. How somatosensory maps are formed and relayed into the neocortex remain essential questions in developmental neuroscience. Here, we will present our current knowledge on whisker map transfer in the mouse model, with the goal of linking embryonic and postnatal studies into a comprehensive framework. PMID:25020201

  4. [Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

    PubMed

    Voronina, T A; Guzevatykh, L S; Trofimov, S S

    2005-01-01

    Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups. PMID:15934357

  5. The effects of early-life predator stress on anxiety- and depression-like behaviors of adult rats.

    PubMed

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  6. The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

    PubMed Central

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  7. Long-term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock.

    PubMed

    Tyler, K; Moriceau, S; Sullivan, R M; Greenwood-van Meerveld, B

    2007-09-01

    Our goal was to examine the relationship between early life trauma and the development of visceral hypersensitivity in later life in irritable bowel syndrome (IBS). Rat pups underwent neonatal conditioning: (i) paired odour-shock, where odour is a predictable shock signal, (ii) unpaired odour-shock, where odour is an unpredictable shock signal or (iii) control odour-only with odour presentations and handling without shock. At maturity, colorectal sensitivity was measured as a visceromotor behavioural response. In adulthood, colorectal distension (CRD) induced a pressure-dependent increase in the number of abdominal muscle contractions all three experimental groups. However, compared to animals that had received control odour-only presentations in infancy, there was an attenuated response to CRD in animals previously exposed to neonatal predictable shock pups and an exaggerated response in the animals previously exposed to neonatal unpredictable shock. Adult responses to CRD were altered by infant experience with shock trauma. However, depending on the context of that early life trauma, there are major differences between the long-term effects of that early life trauma on colonic sensitivity compared to controls. These results strengthen the link between early life trauma and adult IBS, and suggest that unpredictable trauma is a critical factor for later life disorders. PMID:17727395

  8. Responsiveness to cocaine challenge in adult rats following prenatal exposure to cocaine.

    PubMed

    Heyser, C J; Rajachandran, L; Spear, N E; Spear, L P

    1994-09-01

    Adult rats that were gestationally exposed to cocaine and control offspring were examined for their sensitivity to challenge doses of cocaine. Offspring were derived from Sprague-Dawley dams that had received subcutaneous injections of 40 mg/kg per 3 cc cocaine hydrochloride daily on gestational days 8-20, pair-fed dams that were injected with saline, and nontreated control dams. In order to investigate the sensitivity to challenge doses of cocaine, offspring were assessed in adulthood for locomotor activity, cocaine drug discrimination, and the time course of cocaine in brain tissue following acute cocaine challenge. Adult offspring prenatally exposed to cocaine were observed to exhibit a reduced sensitivity to the discriminative stimulus effects of cocaine as evidenced by a significant shift to the right in the dose-response curve of cocaine discrimination. No prenatal treatment effects were observed in terms of the temporal patterns of cocaine discrimination or with regard to brain levels of cocaine. In addition, baseline locomotor activity and locomotor responses to challenge doses of cocaine were comparable across the prenatal treatment groups. Thus, prenatal cocaine exposure reduced sensitivity of offspring to the discriminative stimulus properties of cocaine without altering either the distribution of cocaine to the brain or the sensitivity of the offspring to the locomotor stimulant effects of cocaine. PMID:7862930

  9. 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

  10. Treprostinil potentiates the positive inotropic effect of catecholamines in adult rat ventricular cardiomyocytes

    PubMed Central

    Fontana, M; Olschewski, H; Olschewski, A; Schlüter, K-D

    2007-01-01

    Background and purpose: Prostanoids have been shown to improve exercise tolerance, hemodynamics and quality of life in patients with pulmonary arterial hypertension (PAH). We investigated whether treprostinil exerts direct contractile effects on cardiomyocytes that may explain partly the beneficial effects of these drugs. Experimental approach: Ventricular cardiomyocytes from adult rats were paced at a constant frequency of 0.5 to 2.0 Hz and cell shortening was monitored via a cell edge detection system. Twitch amplitudes, expressed as percent cell shortening of the diastolic cell length, and maximal contraction velocity, relaxation velocity, time to peak of contraction and time to reach 50% of relaxation were analyzed. Key results: Treprostinil (0.15 – 15 ng ml−1) slightly increased contractile dynamics of cardiomyocytes at clinically relevant concentrations. However, the drug significantly improved cell shortening of cardiomyocytes in the presence of isoprenaline, a β-adrenoceptor agonist. Treprostinil exerted this effect at all beating frequencies under investigation. Treprostinil mimicked this potentiating effect in a Langendorff preparation as well. The potentiating effect of treprostinil on isoprenaline-dependent cell shortening was no longer seen after phosphodiesterase inhibition. Long-term cultivation of cardiomyocytes with treprostinil did not modify load free cell shortening of these cells, but reduces the duration of contraction. Conclusions and implications: We conclude that the clinically used prostanoid treprostinil potentiates the positive inotropic effects of catecholamines in adult ventricular cardiomyocytes. This newly described effect may contribute to the beneficial clinical effects of prostanoids in patients with PAH. PMID:17533419

  11. Adult rat bone marrow stromal cells express genes associated with dopamine neurons

    SciTech Connect

    Kramer, Brian C.; Woodbury, Dale . E-mail: WOODBURYDL@AOL.COM; Black, Ira B.

    2006-05-19

    An intensive search is underway to identify candidates to replace the cells that degenerate in Parkinson's disease (PD). To date, no suitable substitute has been found. We have recently found that adult rat bone marrow stromal cells (MSCs) can be induced to assume a neuronal phenotype in vitro. These findings may have particular relevance to the treatment of PD. We now report that adult MSCs express multiple dopaminergic genes, suggesting that they are potential candidates for cell therapy. Using RT-PCR, we have examined families of genes that are associated with the development and/or survival of dopaminergic neurons. MSCs transcribe a variety of dopaminergic genes including patched and smoothened (components of the Shh receptor), Gli-1 (downstream mediator of Shh), and Otx-1, a gene associated with formation of the mesencephalon during development. Furthermore, Shh treatment elicits a 1.5-fold increase in DNA synthesis in cultured MSCs, suggesting the presence of a functional Shh receptor complex. We have also found that MSCs transcribe and translate Nurr-1, a nuclear receptor essential for the development of dopamine neurons. In addition, MSCs express a variety of growth factor receptors including the glycosyl-phosphatidylinositol-anchored ligand-binding subunit of the GDNF receptor, GFR{alpha}1, as well as fibroblast growth factor receptors one and four. The expression of genes that are associated with the development and survival of dopamine neurons suggests a potential role for these cells in the treatment of Parkinson's disease.

  12. Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

    PubMed

    Huang, Luping Z; Liu, Xuhong; Griffith, William H; Winzer-Serhan, Ursula H

    2007-12-01

    Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences. PMID:18085887

  13. Prenatal ethanol exposure affects temperature responses of adult rats to pentobarbital and diazepam alone and in combination with ethanol.

    PubMed

    Taylor, A N; Branch, B J; Randolph, D; Hill, M A; Kokka, N

    1987-06-01

    Long-term effects of prenatal alcohol exposure on body temperature responses to pentobarbital and diazepam and to either drug in combination with ethanol were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet during the last 2 weeks of gestation. Adult offspring of pair-fed and chow-fed dams served as nutritional and normal controls, respectively. Pentobarbital (6.25-25.0 mg/kg) and diazepam (2.5-10.0 mg/kg) produced significantly greater dose-related hypothermic responses in females than males. Following either pentobarbital or diazepam administration female prenatally ethanol-exposed (E) rats responded with a greater fall in body temperature than the controls. Significantly greater hypothermia occurred in both male and female E rats than in controls when ethanol (1.5 g/kg) was administered together with pentobarbital or diazepam. However, the drug combinations did not produce additive effects on body temperature in any prenatal treatment group. Pentobarbital produced acute cross-tolerance to ethanol while diazepam potentiated ethanol's effect. These studies confirm and extend our previous findings of enhanced hypothermic responses to ethanol in adult rats exposed to ethanol in utero and indicate that maternal alcohol consumption produces long-term effects on the central thermoregulatory systems of offspring. PMID:3307489

  14. Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord

    PubMed Central

    Yan, Jun; Xu, Leyan; Welsh, Annie M; Hatfield, Glen; Hazel, Thomas; Johe, Karl; Koliatsos, Vassilis E

    2007-01-01

    Background Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC) transplants have shown either poor differentiation or a preferential choice of glial lineages. Methods and Findings In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. Conclusions NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major challenges remain

  15. Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

    PubMed Central

    Chan, Jackie K. W.; Fanucchi, Michelle V.; Anderson, Donald S.; Abid, Aamir D.; Wallis, Christopher D.; Dickinson, Dale A.; Kumfer, Benjamin M.; Kennedy, Ian M.; Wexler, Anthony S.; Van Winkle, Laura S.

    2011-01-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth. PMID:21914721

  16. Characterization of Amino Acid Profile and Enzymatic Activity in Adult Rat Astrocyte Cultures.

    PubMed

    Souza, Débora Guerini; Bellaver, Bruna; Hansel, Gisele; Arús, Bernardo Assein; Bellaver, Gabriela; Longoni, Aline; Kolling, Janaina; Wyse, Angela T S; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-07-01

    Astrocytes are multitasking players in brain complexity, possessing several receptors and mechanisms to detect, participate and modulate neuronal communication. The functionality of astrocytes has been mainly unraveled through the study of primary astrocyte cultures, and recently our research group characterized a model of astrocyte cultures derived from adult Wistar rats. We, herein, aim to characterize other basal functions of these cells to explore the potential of this model for studying the adult brain. To characterize the astrocytic phenotype, we determined the presence of GFAP, GLAST and GLT 1 proteins in cells by immunofluorescence. Next, we determined the concentrations of thirteen amino acids, ATP, ADP, adenosine and calcium in astrocyte cultures, as well as the activities of Na(+)/K(+)-ATPase and acetylcholine esterase. Furthermore, we assessed the presence of the GABA transporter 1 (GAT 1) and cannabinoid receptor 1 (CB 1) in the astrocytes. Cells demonstrated the presence of glutamine, consistent with their role in the glutamate-glutamine cycle, as well as glutamate and D-serine, amino acids classically known to act as gliotransmitters. ATP was produced and released by the cells and ADP was consumed. Calcium levels were in agreement with those reported in the literature, as were the enzymatic activities measured. The presence of GAT 1 was detected, but the presence of CB 1 was not, suggesting a decreased neuroprotective capacity in adult astrocytes under in vitro conditions. Taken together, our results show cellular functionality regarding the astrocytic role in gliotransmission and neurotransmitter management since they are able to produce and release gliotransmitters and to modulate the cholinergic and GABAergic systems. PMID:26915106

  17. Auditory behaviour and brainstem histochemistry in adult rats with characterized ear damage after neonatal ossicle ablation or cochlear disruption.

    PubMed

    Paterson, J A; Hosea, E W

    1993-02-26

    Binaural and monaural ossicle ablation in neonate rats before the time of onset of auditory input resulted in hearing deficits as detected by behavioural responses to sound stimuli in these rats as young adults. Cochlear disruption at the same neonatal age similarly resulted in the absence of startle reflexes in many of the rats. When the middle and inner ears of the rats were analysed postmortem in serial sections, it was observed that most ears after neonatal ossicle ablation contained only small remnants of the malleus-incus unit, separated from the stapes; in other ears an apparent continuity of ossicles had been restored. The rats with blind-ending ear canals and ossicle atrophy were those that had shown little response to sound stimuli. In the cochlear-disrupted rats, those with modiolar damage and loss of most spiral ganglion cells had shown substantial impairment of sound perception, even in some rats with only monaural modiolar loss. The chronic conduction deficit caused by neonatal ossicle removal did not result in detectable differences in relative cytochrome oxidase activity in the dorsal cochlear nuclei and central nucleus of the inferior colliculus. For monaurally ossicle-ablated rats, quantitation of the average intensity of enzyme reaction product in sections of dorsal or ventral cochlear nuclei, or central nucleus, did not reveal a difference between operated and non-operated sides. However, in binaurally ossicle-ablated rats, the relative enzyme activity in the anteroventral cochlear nuclei was reduced in comparison to this nucleus in control rats. The volume of the anteroventral cochlear nucleus in rats that had had neonatal binaural cochlear disruption was reduced relative to the volume in control rats or in rats that had had binaural ossicle ablation (P < 0.001); the latter procedure did not result in a statistically significant difference from controls in AVCN volume. In cochlear-operated rats with monaural modiolar damage, the AVCN

  18. Enriched Environment Altered Aberrant Hippocampal Neurogenesis and Improved Long-Term Consequences After Temporal Lobe Epilepsy in Adult Rats.

    PubMed

    Zhang, Xiaoqian; Liu, Tingting; Zhou, Zhike; Mu, Xiaopeng; Song, Chengguang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

    2015-06-01

    Abnormal hippocampal neurogenesis is thought to contribute to cognitive impairments in chronic temporal lobe epilepsy (TLE). Stromal cell-derived factor-1 (SDF-1) and its specific receptor CXCR4 play important roles in neurogenesis. We investigated whether enriched environment (EE) might be beneficial for TLE. Adult rats were randomly assigned as control rats, rats subjected to status epilepticus (SE), or post-SE rats treated with EE for 30 days. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze. Western blot was used to measure the expression of SDF-1 and CXCR4 in the hippocampus. In the present study, we found the TLE model resulted in aberrant neurogenesis such as reduced proliferation, intensified dendritic development of newborn neurons, as well as spontaneous seizures and cognitive impairments. More importantly, EE treatment significantly increased the cell proliferation and survival, extended the apical dendrites, and delayed the attenuation of the expression of SDF-1 and CXCR4, accompanied by decreased long-term seizure activity and improved cognitive impairments in adult rats after TLE. These results provided morphological evidence that EE might be beneficial for treating TLE. PMID:25946980

  19. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats

    PubMed Central

    Pistilli, Emidio E.

    2008-01-01

    In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle. PMID:18555009

  20. The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

    PubMed

    Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

    2015-09-14

    Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. PMID:26238258

  1. Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

    PubMed Central

    Aubele, T.; Kaufman, R.; Montalment, F.; Kritzer, M.F.

    2008-01-01

    Recent studies in adult male rats have shown that gonadal hormones influence performance on certain working memory and other types of cognitive tasks that are sensitive to lesions of the medial and/or orbital prefrontal cortices. This study asked whether gonadal hormone modulation of prefrontal cortical function in males also extends to the perirhinal division of the rat prefrontal cortex. Specifically, sham-operated control, gonadectomized, and gonadectomized rats supplemented with testosterone propionate or estradiol were tested on a spontaneous novel object recognition task, a paradigm where performance has been shown to be impaired by perirhinal cortical lesions. Using analyses of variance, regression analyses and post-hoc testing to evaluate group differences, it was found that during both the sample and test trials of the task all four groups spent similar absolute and proportional amounts of time ambulating, rearing, stationary, and exploring the two objects present. All groups also explored each of the two identical objects present during sample trials equally. However, during the test trials, only the control and gonadectomized rats given testosterone showed the expected increase in exploration of the novel objects presented, whereas the gonadectomized and gonadectomized, estradiol-supplemental groups continued to explore the novel and familiar objects equally. That regression analyses also identified significant correlations between low bulbospongiosus muscle weight and impaired novel vs. familiar object discrimination further indicates that gonadectomy in adult male rats adversely affects spontaneous novel object recognition in an androgen-sensitive, estrogen-insensitive manner. PMID:18511051

  2. Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats

    PubMed Central

    Khimsuksri, Sawita; Wyss, J. Michael; Thaeomor, Atcharaporn; Paphangkorakit, Jarin; Jirakulsomchok, Dusit; Roysommuti, Sanya

    2016-01-01

    Perinatal taurine excess or deficit influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed normal rat chow with 3% β-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Their male offspring were fed normal rat chow and tap water throughout the experiment. At 8–10 weeks of age, blood chemistry, arterial pressure, heart rate and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low (0.3–0.5 Hz) and high frequency (0.5–4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups, while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve and arterial pressure power spectral densities in the 0.3–4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very low frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in

  3. GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat.

    PubMed

    Ayala-Sarmiento, Alberto E; Estudillo, Enrique; Pérez-Sánchez, Gilberto; Sierra-Sánchez, Arturo; González-Mariscal, Lorenza; Martínez-Fong, Daniel; Segovia, José

    2016-09-01

    Growth arrest specific 1 (GAS1) is a GPI-anchored protein that inhibits proliferation when overexpressed in tumors but during development it promotes proliferation and survival of different organs and tissues. This dual ability is caused by its capacity to interact both by inhibiting the signaling induced by the glial cell line-derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. GAS1 is expressed as membrane bound in different organs and as a secreted form by glomerular mesangial cells. In the developing central nervous system, GAS1 is found in neural progenitors; however, it continues to be expressed in the adult brain. Here, we demonstrate that soluble GAS1 is present in the cerebrospinal fluid (CSF) and it is expressed in the choroid plexus (CP) of the adult rat, the main producer of CSF. Additionally, we confirm the presence of GAS1 in blood plasma and liver of the adult rat, the principal source of blood plasma proteins. The pattern of expression of GAS1 is perivascular in both the CP and the liver. In vitro studies show that the fibroblast cell line NIH/3T3 expresses one form of GAS1 and releases two soluble forms into the supernatant. Briefly, in the present work, we show the presence of GAS1 in adult rat body fluids focusing in the CSF and the CP, and suggest that secreted GAS1 exists as two different isoforms. PMID:27225491

  4. Temperament moderates the influence of periadolescent social experience on behavior and adrenocortical activity in adult male rats

    PubMed Central

    Caruso, M.J.; McClintock, M.K.; Cavigelli, S.A.

    2014-01-01

    Adolescence is a period of significant behavioral and physiological maturation, particularly related to stress responses. Animal studies that have tested the influence of adolescent social experiences on stress-related behavioral and physiological development have led to complex results. We used a rodent model of neophobia to test the hypothesis that the influence of adolescent social experience on adult behavior and adrenocortical function is modulated by preadolescent temperament. Exploratory activity was assessed in 53 male Sprague-Dawley rats to classify temperament and then they were housed in one of three conditions during postnatal days (PND) 28-46: (1) with familiar kin, (2) with novel social partners, or (3) individually with no social partners. Effects on adult adrenocortical function were evaluated from fecal samples collected while rats were individually-housed and exposed to a 1-hour novel social challenge during PND 110-114. Adolescent-housing with novel or no social partners led to reduced adult glucocorticoid production compared to adolescent-housing with familiar littermates. Additionally, highly-exploratory pre-weanling rats that were housed with novel social partners during adolescence exhibited increased exploratory behavior and a more rapid return to basal glucocorticoid production in adulthood compared to those housed with familiar or no social partners during adolescence and compared to low-exploratory rats exposed to novel social partners. In sum, relatively short-term adolescent social experiences can cause transient changes in temperament and potentially longer-term changes in recovery of glucocorticoid production in response to adult social challenges. Furthermore, early temperament may modulate the influence of adolescent experiences on adult behavioral and adrenocortical function. PMID:25066485

  5. Peripheral inflammation facilitates Abeta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord.

    PubMed

    Baba, H; Doubell, T P; Woolf, C J

    1999-01-15

    Whole-cell patch-clamp recordings were made from substantia gelatinosa (SG) neurons in thick adult rat transverse spinal cord slices with attached dorsal roots to study changes in fast synaptic transmission induced by peripheral inflammation. In slices from naive rats, primary afferent stimulation at Abeta fiber intensity elicited polysynaptic EPSCs in only 14 of 57 (25%) SG neurons. In contrast, Abeta fiber stimulation evoked polysynaptic EPSCs in 39 of 62 (63%) SG neurons recorded in slices from rats inflamed by an intraplantar injection of complete Freund's adjuvant (CFA) 48 hr earlier (p < 0.001). Although the peripheral inflammation had no significant effect on the threshold and conduction velocities of Abeta, Adelta, and C fibers recorded in dorsal roots, the mean threshold intensity for eliciting EPSCs was significantly lower in cells recorded from rats with inflammation (naive: 33.2 +/- 15.1 microA, n = 57; inflamed: 22.8 +/- 11.3 microA, n = 62, p < 0.001), and the mean latency of EPSCs elicited by Abeta fiber stimulation in CFA-treated rats was significantly shorter than that recorded from naive rats (3.3 +/- 1.8 msec, n = 36 vs 6.0 +/- 3.5 msec, n = 12; p = 0.010). Abeta fiber stimulation evoked polysynaptic IPSCs in 4 of 25 (16%) cells recorded from naive rat preparations and 14 of 26 (54%) SG neurons from CFA-treated rats (p < 0.001). The mean threshold intensity for IPSCs was also significantly lower in CFA-treated rats (naive: 32.5 +/- 15.7 microA, n = 25; inflamed: 21. 9 +/- 9.9 microA, n = 26, p = 0.013). The facilitation of Abeta fiber-mediated input into the substantia gelatinosa after peripheral inflammation may contribute to altered sensory processing. PMID:9880605

  6. Some histological effects of chronic administration of chloroquine on the medial geniculate body of adult wistar rat.

    PubMed

    Adjene, J O; Caxton-Martins, A E

    2006-06-01

    Some histological effects of chronic administration of chloroquine commonly used for prophylaxis or treatment of malaria. rheumatoid arthritis and lupus erythematosus on the medial geniculate body (MGB) of adult wistar rats was carefully studied. The rats of both sexes (n= 18), average weight of 184g were randomly assigned into treatment (n= 10) and control (n=7) groups. The rats in the treatment group received 2mg/kg body weight of chloroquine base dissolved in distilled water daily for fourteen days through the orogastric tube administration while the control rats received equal volume of distilled water daily through the same route. The rats were fed with rat pellets purchased from Topfeed Ltd. Sapele. Delta State. Nigeria and given water liberally and were then sacrificed on day fifteen of the experiment. The MGB were carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H & E and thionin methods. The histological findings after H & E methods indicated that the treated sections of the MGB showed faintly reduced nuclei size, with the presence of many autophagic vacuoles and degenerative neurons when compared to the control sections. On the other hand. the thionin method indicated that the treated sections showed sparsely distributed neurons, which stain less intensely when compared with the control. The nissl substance in some of the neurons appeared degenerative while some hypertrophied with some vacuolations. These findings indicated that chronic administration of chloroquine has a deleterious effect on the neurons and nissl substance of the MGB. Chloroquine may probably have adverse effects on auditory sensibilities by its deleterious effects on the nerve cells and nissl substances of the MGB of the adult wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out. PMID:17209307

  7. Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove TaskS⃞

    PubMed Central

    Zarcone, Troy J.; Davis, Paul F.; Ozias, Marlies K.; Fowler, Stephen C.

    2011-01-01

    Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylphenidate (2.5 and 5.0 mg/kg s.c.) were examined in periadolescent [postnatal days (P) 35 and 42] and young adult (P70), male Long-Evans rats using a three-period locomotor activity paradigm that affords inferences about exploration, habituation, and attention to a novel stimulus (an “alcove”) in a familiar environment in a single test session. In the first test period, P35 and P42 rats were more active than P70 rats, and methylphenidate increased locomotion in a dose-related manner. The introduction of a novel spatial stimulus in the third test period revealed a significant interaction of dose and age such that P70 rats exhibited dose-related increases in distance traveled, but P35 rats did not. Furthermore, methylphenidate dose-relatedly disrupted the rats' tendency to spend increasing amounts of time in the alcove across the test period at P70 but not at P35. Brain and serum methylphenidate concentrations were significantly lower at P35 than at P70, with intermediate levels at P42. Developmental differences in dopaminergic neurochemistry were also observed, including increased dopamine content in the caudate-putamen, nucleus accumbens, and frontal cortex and decreased densities of D1-like receptors in the frontal cortex in P70 than in P42 rats. These results raise the possibility that children and adults may respond differently when treated with this drug, particularly in situations involving response to novelty and that these effects involve developmental differences in pharmacokinetics and dopaminergic neurochemistry. PMID:21205916

  8. Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex

    PubMed Central

    Mora-Bermúdez, Felipe; Taverna, Elena; Haffner, Christiane; Fu, Jun; Anastassiadis, Konstantinos; Stewart, A. Francis; Huttner, Wieland B.

    2015-01-01

    The evolutionary expansion of the neocortex in mammals has been linked to enlargement of the subventricular zone (SVZ) and increased proliferative capacity of basal progenitors (BPs), notably basal radial glia (bRG). The transcription factor Pax6 is known to be highly expressed in primate, but not mouse, BPs. Here, we demonstrate that sustaining Pax6 expression selectively in BP-genic apical radial glia (aRG) and their BP progeny of embryonic mouse neocortex suffices to induce primate-like progenitor behaviour. Specifically, we conditionally expressed Pax6 by in utero electroporation using a novel, Tis21–CreERT2 mouse line. This expression altered aRG cleavage plane orientation to promote bRG generation, increased cell-cycle re-entry of BPs, and ultimately increased upper-layer neuron production. Upper-layer neuron production was also increased in double-transgenic mouse embryos with sustained Pax6 expression in the neurogenic lineage. Strikingly, increased BPs existed not only in the SVZ but also in the intermediate zone of the neocortex of these double-transgenic mouse embryos. In mutant mouse embryos lacking functional Pax6, the proportion of bRG among BPs was reduced. Our data identify specific Pax6 effects in BPs and imply that sustaining this Pax6 function in BPs could be a key aspect of SVZ enlargement and, consequently, the evolutionary expansion of the neocortex. PMID:26252244

  9. Effect of TiO2 nanoparticles on emotional behavior and biochemical parameters in adult Wistar rats.

    PubMed

    Amara, Salem; Khemissi, Wahid; Mrad, Imen; Rihane, Naima; Ben Slama, Imen; Mir, Lassaad E; Jeljeli, Mustapha; Ben Rhouma, Khemais; Abdelmelek, Hafedh; Sakly, Mohsen

    2013-06-01

    The rapidly developing field of nanotechnology is becoming a potential source for human exposure to nanoparticles. Titanium dioxide (TiO2) nanoparticles have been widely produced in industrial processes for several years. The aim of this study was to investigate the effects of TiO2 nanoparticles on plasmatic biochemical parameters and the emotional behavior in adult Wistar rats. Rats were treated by intraperitoneal injection of TiO2 nanoparticles (20-30 nm) at a dose of 25 mg/kg. For toxicity evaluation of nanoparticles sample, body weight, organ coefficient, blood biochemistry panel assay (AST, ALT, LDH, uric acid, creatinine, and glucose content) and emotional behavior parameters were determined. Sub-acute TiO2 nanoparticles treatment decreased the body weight, but increased the relative brain weight. Biochemical assessment in plasma samples showed that TiO2 nanoparticles injection increased uric acid concentration and AST activity in rats. However, the same treatment decreased the creatinine level, but had no effect on glucose concentration, ALT and LDH activity. The emotional behavior of control and treated rats was tested in elevated plus-maze. Interestingly, our results showed that TiO2-treated rats spent more time in the secured closed arms and entered the anxiogenic open arms less frequently than control. Our results suggest that TiO2 nanoparticles intoxication could altered biochemical parameters related to changes in organ function and leads to emotional behavior impairment of rats. PMID:23682022

  10. Altered dendritic arborization of amygdala neurons in young adult rats orally intubated with Clitorea ternatea aqueous root extract.

    PubMed

    Rai, Kiranmai S; Murthy, K Dilip; Rao, Muddanna S; Karanth, K Sudhakar

    2005-07-01

    Young adult (60 day old) Wistar rats of either sex were orally intubated with 50 mg/kg body weight and 100 mg/kg body weight of aqueous root extract of Clitoria ternatea (CTR) for 30 days, along with age-matched saline controls. These rats were then subjected to passive avoidance tests and the results from these studies showed a significant increase in passive avoidance learning and retention. Subsequent to the passive avoidance tests, these rats were killed by decapitation. The amygdala was processed for Golgi staining and the stained neurons were traced using a camera lucida and analysed. The results showed a significant increase in dendritic intersections, branching points and dendritic processes arising from the soma of amygdaloid neurons in CTR treated rats especially in the 100 mg/kg group of rats, compared with age-matched saline controls. This improved dendritic arborization of amygdaloid neurons correlates with the increased passive avoidance learning and memory in the CTR treated rats as reported earlier. The results suggest that Clitoria ternatea aqueous root extract enhances memory by increasing the functional growth of neurons of the amygdala. PMID:16161034

  11. Prolongation of GFP-expressed skin graft after intrathymic injection of GFP positive splenocytes in adult rat

    NASA Astrophysics Data System (ADS)

    Hakamata, Yoji; Igarashi, Yuka; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    GFP is a fluorescent product of the jellyfish Aequorea victoria and has been used for a variety of biological experiments as a reporter molecule. While GFP possesses advantages for the non-invasive imaging of viable cells, GFP-positive cells are still considered potential xeno-antigens. It is difficult to observe the precise fate of transplanted cells/organs in recipients without immunological control. The aim of this study was to determine whether intrathymic injection of GFP to recipients and the depletion of peripheral lymphocytes could lead to donor-specific unresponsiveness to GFP-expressed cell. LEW rats were administered intraperitoneally with 0.2 ml of anti-rat lymphocyte serum (ALS) 1 day prior to intrathymic injection of donor splenocytes or adeno-GFP vector. Donor cells and vector were non-invasively inoculated into the thymus under high frequency ultrasound imaging using an echo-guide. All animals subsequently received a 7 days GFP-expressed skin graft from the same genetic background GFP LEW transgenic rat. Skin graft survival was greater in rats injected with donor splenocytes (23.6+/-9.1) compared with adeno-GFP (13.0+/-3.7) or untreated control rats (9.5+/-1.0). Intrathymic injection of donor antigen into adult rats can induce donor-specific unresponsiveness. Donor cells can be observed for a long-term in recipients with normal immunity using this strategy.

  12. Repeated-dose liver and gastrointestinal tract micronucleus assays with CI Solvent Yellow 14 (Sudan I) using young adult rats.

    PubMed

    Matsumura, Shoji; Ikeda, Naohiro; Hamada, Shuichi; Ohyama, Wakako; Wako, Yumi; Kawasako, Kazufumi; Kasamatsu, Toshio; Nishiyama, Naohiro

    2015-03-01

    The in vivo genotoxicity of CI Solvent Yellow 14 (Sudan I) was examined using repeated-dose liver and gastrointestinal tract micronucleus (MN) assays in young adult rats. Sudan I is a mono-azo dye based on aniline and 1-amino-2-hydroxynaphthalene. This dye was demonstrated as a rat liver carcinogen in a National Toxicology Program (NTP) bioassay, and genotoxicity was noted in a rat bone marrow micronucleus (BMMN) assay. In the present study, Sudan I was administered orally to rats for 14-days, and the MN frequency in the liver, stomach, colon, and bone marrow were analyzed. The frequency of micronucleated hepatocytes (MNHEPs) was not significantly increased by the administration of the Sudan I. Gastrointestinal tract MNs were also not induced. However, in the BMMN assay, a significant increase in micronucleated immature erythrocytes (MNIMEs) was observed in a dose-dependent manner. While Sudan I has been reported to lack hepatic genotoxicity, it has also exhibited tumor-promoting activities. These results are consistent with the lack of induction of MN in the hepatocytes. The lack of MN induction in cells of the gastrointestinal tract was also logical because azo-compounds are reported to be unlikely to induce DNA damage in the rat gut. The repeated-dose rat liver and gastrointestinal tract MN assays have the potential to be used in the evaluation of the genotoxicity of a chemical in each organ in accordance with its mode of action. PMID:25892626

  13. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  14. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats.

    PubMed

    Oshiro, W M; Beasley, T E; McDaniel, K L; Evansky, P A; Martin, S A; Moser, V C; Gilbert, M E; Bushnell, P J

    2015-01-01

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoline alone (E0) and gasoline with 15% or 85% ethanol (E15 and E85, respectively). Rat dams were exposed for 6.5h daily to the vapors at concentrations of 0, 3000, 6000, or 9000 ppm in inhalation chambers from gestational day (GD) 9 through 20. Cage controls (offspring of non-exposed dams that remained in the animal facility during these exposures) were also assessed in the E0 experiment, but showed no consistent differences from the offspring of air-exposed controls. Offspring were tested as adults with trace fear conditioning, Morris water maze, or appetitive operant responding. With fear conditioning, no significant effects were observed on cue or context learning. In the water maze, there were no differences in place learning or escaping to a visible platform. However, during the reference memory probe (no platform) male rats exposed prenatally to E85 vapor (6000 and 9000 ppm) failed to show a bias for the target quadrant. Across studies, females (treated and some controls) were less consistent in this measure. Males showed no differences during match-to-place learning (platform moved each day) in any experiment and females showed only transient differences in latency and path length in the E0 experiment. Similarly, no differences were observed in delayed match-to-sample operant performance of E0 males or females; thus this test was not used to evaluate effects of E15 or E85 vapors. During choice reaction time assessments (only males were tested) decision and movement times were unimpaired by any prenatal exposure, while anticipatory responses were increased by vapors of E0 (9000 ppm) and E15 (6000 and 9000 ppm), and the latter group also showed reduced accuracy. E85 vapors did not disrupt

  15. The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats.

    PubMed

    Escárcega-González, Carlos Enrique; Reynoso-Andeola, Irma Guadalupe; Jaramillo-Juárez, Fernando; Martínez-Ruvalcaba, Haydée; Posadas Del Rio, Francisco A

    2016-01-01

    The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200-300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student's t-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity of γ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0-5, 5-24, 24-48, and 48-72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5-24, 24-48, and 48-72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats. PMID:27042354

  16. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism. PMID:26583437

  17. Muscarinic acetylcholine receptor modulation of mu (mu) opioid receptors in adult rat sphenopalatine ganglion neurons.

    PubMed

    Margas, Wojciech; Mahmoud, Saifeldin; Ruiz-Velasco, Victor

    2010-01-01

    The sphenopalatine ganglion (SPG) neurons represent the parasympathetic branch of the autonomic nervous system involved in controlling cerebral blood flow. In the present study, we examined the coupling mechanism between mu (mu) opioid receptors (MOR) and muscarinic acetylcholine receptors (mAChR) with Ca(2+) channels in acutely dissociated adult rat SPG neurons. Successful MOR activation was recorded in approximately 40-45% of SPG neurons employing the whole cell variant of the patch-clamp technique. In addition, immunofluorescence assays indicated that MOR are not expressed in all SPG neurons while M(2) mAChR staining was evident in all neurons. The concentration-response relationships generated with morphine and [d-Ala2-N-Me-Phe4-Glycol5]-enkephalin (DAMGO) showed IC(50) values of 15.2 and 56.1 nM and maximal Ca(2+) current inhibition of 26.0 and 38.7%, respectively. Activation of MOR or M(2) mAChR with morphine or oxotremorine-methiodide (Oxo-M), respectively, resulted in voltage-dependent inhibition of Ca(2+) currents via coupling with Galpha(i/o) protein subunits. The acute prolonged exposure (10 min) of neurons to morphine or Oxo-M led to the homologous desensitization of MOR and M(2) mAChR, respectively. The prolonged stimulation of M(2) mAChR with Oxo-M resulted in heterologous desensitization of morphine-mediated Ca(2+) current inhibition, and was sensitive to the M(2) mAChR blocker methoctramine. On the other hand, when the neurons were exposed to morphine or DAMGO for 10 min, heterologous desensitization of M(2) mAChR was not observed. These results suggest that in rat SPG neurons activation of M(2) mAChR likely modulates opioid transmission in the brain vasculature to adequately maintain cerebral blood flow. PMID:19889856

  18. Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats

    NASA Technical Reports Server (NTRS)

    Tash, Joseph S.; Johnson, Donald C.; Enders, George C.

    2002-01-01

    The International Space Station will allow extended habitation in space and long-term exposure to microgravity (microG). A concern is the impact of long-term microG exposure on the ability of species to reproduce. The model often used to simulate microG is rat hindlimb suspension (HLS), where the hindlimbs are elevated above the cage floor with a tail harness. Experiments described here are the first to examine the effect of long-term HLS on testicular function in adult male rats. Free-roaming (controls), animals with only the tail harnessed but hindlimbs in contact with the cage floor (TO), and HLS animals were tested for 6 wk. Cryptorchidism was prevented in TO and HLS animals by partial constriction of the inguinal canal with sutures. All parameters were compared at the end of the 6-wk experiment. Testicular weights and spermatogenesis were significantly reduced by HLS, such that no spermatogenic cells beyond round spermatids were present and epididymides were devoid of mature sperm. In many tubules, loss of all germ cells, except a few spermatogonia, resulting in histopathology similar to the Sertoli cell, was observed. Spermatogenesis appeared unaffected in control and TO animals. Sertoli and Leydig cell appearance, testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and epididymal and seminal vesicle weight were unchanged by HLS. Cortisone was not elevated by HLS; thus stress may not be a factor. These results demonstrate that spermatogenesis is severely inhibited by long-term HLS, whereas testicular androgen production is not. These results have significant implications regarding serious effects of long-term exposure to microG on the reproductive capability of scrotal mammals, including humans.

  19. The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats

    PubMed Central

    Reynoso-Andeola, Irma Guadalupe; Jaramillo-Juárez, Fernando; Martínez-Ruvalcaba, Haydée; Posadas del Rio, Francisco A.

    2016-01-01

    The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200–300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student's t-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity of γ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0–5, 5–24, 24–48, and 48–72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5–24, 24–48, and 48–72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats. PMID:27042354

  20. Spinal Interneurons and Forelimb Plasticity after Incomplete Cervical Spinal Cord Injury in Adult Rats

    PubMed Central

    Rombola, Angela M.; Rousseau, Celeste A.; Mercier, Lynne M.; Fitzpatrick, Garrett M.; Reier, Paul J.; Fuller, David D.; Lane, Michael A.

    2015-01-01

    Abstract Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer – pseudorabies virus – was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration. PMID:25625912

  1. Effects of triadimefon on extracellular dopamine, DOPAC, HVA and 5-HIAA in adult rat striatum.

    PubMed

    Gagnaire, François; Micillino, Jean-Claude

    2006-01-16

    Triadimefon has been shown to inhibit monoamine uptake, bind to the dopamine (DA) transporter, and stimulate dopamine efflux in rat brain tissue, in vitro. To determine whether these changes also occur in the intact animal and to study the reversibility of the effects observed, we used in vivo microdialysis to determine changes in the concentrations of DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in the striatal dialysates from free moving adult rats after exposure to triadimefon 50, 100 and 200mg/kg, i.p. Triadimefon induced a gradual dose- and time-dependent accumulation of extracellular DA accompanied by a small increase in the HVA and 5-HIAA concentrations. These changes were still present 24h after treatment in the group treated with 200mg/kg and had vanished 48 h after treatment. In contrast to the DA efflux induced by S(+)-amphetamine (2mg/kg, i.p.), that induced by triadimefon was totally inhibited by the infusion of 10(-5)M tetrodotoxin (TTX), a voltage-gated Na(+) channel blocker, thus showing that the increase in extracellular DA induced by triadimefon was an action potential-dependent mechanism. GBR 12909 (10mg/kg, i.p.), a dopamine uptake inhibitor, induced a gradual increase in striatal dopamine similar to that induced by triadimefon, whereas the effects on the acid metabolites were not exactly the same. The present results indicate that triadimefon acts in vivo as a DA transporter inhibitor and could also act on the serotoninergic system. PMID:16246478

  2. Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

    PubMed Central

    Gilbert, Mary E.; Sui, Li

    2008-01-01

    Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

  3. Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain.

    PubMed

    Lenkei, Z; Palkovits, M; Corvol, P; Llorens-Cortes, C

    1998-02-01

    Angiotensin II and angiotensin III in the brain exert their various effects by acting on two pharmacologically well-defined receptors, the type-1 (AT1) and the type-2 (AT2) receptors. Receptor binding autoradiography has revealed the dominant presence of AT1 in brain nuclei involved in cardiovascular, body fluid and neuroendocrine control. The cloning of the AT1 complementary DNA has revealed the existence of two receptor subtypes in rodents, AT1A and AT1B. Using specific riboprobes for in situ hybridization, we have previously shown that the AT1A messenger RNA is predominantly expressed in the rat forebrain; in contrast the AT1B subtype predominates in the anterior pituitary. Using a similar technical approach, the aim of the present study was to establish the precise anatomical localization of cells synthetising the AT1A receptor in the adult rat brain. High AT1A messenger RNA expression was found in the vascular organ of the lamina terminalis, the median preoptic nucleus, the subfornical organ, the hypothalamic periventricular nucleus, the parvocellular parts of the paraventricular nucleus, the nucleus of the solitary tract and the area postrema, in agreement with previous autoradiographic studies, describing a high density of AT1 binding sites in these nuclei. In addition, AT1A messenger RNA expression was detected in several brain areas, where no AT1 binding was reported previously. Thus, we identify strong expression of AT1A messenger RNA expression in scattered cells of the lateral parts of the preoptic region, the lateral hypothalamus and several brainstem nuclei. In none of these structures was the AT1B messenger RNA detectable at the microscopic level. In conclusion, it is suggested that angiotensins may exert their central effects on body fluid and cardiovascular homeostasis mainly via the AT1A receptor subtype. PMID:9483539

  4. The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats.

    PubMed

    Karbalaei, Narges; Ghasemi, Asghar; Hedayati, Mehdi; Godini, Aliashraf; Zahediasl, Saleh

    2014-04-01

    Previous studies have recently shown that maternal hypothyroidism leads to impaired glucose metabolism and reduced insulin secretion in adult offspring in rats. The aim of this study was to locate the defect in the insulin secretion pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid (FH) group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An intravenous glucose tolerance test was carried out on 5-month-old male offspring. In in vitro studies, the effects of various secretagogues and inhibitors acting at different levels of the insulin secretion cascade were investigated, and insulin content, insulin secretion and glucokinase activity of the islets were compared. Although insulin content of the FH islets did not differ from that of control islets, insulin secretion from FH islets was reduced when it was challenged by glucose or arginine. Compared with control islets, activities of both hexokinase and glucokinase were also significantly decreased in the FH islets. Although, in both groups, increasing glibenclamide and nifedipine concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased insulin secretion, respectively, the percentage of changes in secretion of FH islets was significantly lower compared with control islets. The response of FH islets to high extracellular potassium concentration and diazoxide was also significantly lower than that of the control islets. These findings demonstrate that impaired insulin secretion in the FH group is probably related to alterations in different steps of the insulin secretion pathway and not in the insulin pool of β-cells. PMID:24097159

  5. Fetal iron deficiency alters the proteome of adult rat hippocampal synaptosomes

    PubMed Central

    Dakoji, Srikanth; Reise, Kathryn H.; Storey, Kathleen K.; Georgieff, Michael K.

    2013-01-01

    Fetal and neonatal iron deficiency results in cognitive impairments in adulthood despite prompt postnatal iron replenishment. To systematically determine whether abnormal expression and localization of proteins that regulate adult synaptic efficacy are involved, we used a quantitative proteomic approach (isobaric tags for relative and absolute quantitation, iTRAQ) and pathway analysis to identify dysregulated proteins in hippocampal synapses of fetal iron deficiency model. Rat pups were made iron deficient (ID) from gestational day 2 through postnatal day (P) 7 by providing pregnant and nursing dams an ID diet (4 ppm Fe) after which they were rescued with an iron-sufficient diet (200 ppm Fe). This paradigm resulted in a 40% loss of brain iron at P15 with complete recovery by P56. Synaptosomes were prepared from hippocampi of the formerly iron-deficient (FID) and always iron-sufficient controls rats at P65 using a sucrose gradient method. Six replicates per group that underwent iTRAQ labeling and LC-MS/MS analysis for protein identification and comparison elucidated 331 differentially expressed proteins. Western analysis was used to confirm findings for selected proteins in the glutamate receptor signaling pathway, which regulates hippocampal synaptic plasticity, a cellular process critical for learning and memory. Bioinformatics were performed using knowledge-based Interactive Pathway Analysis. FID synaptosomes show altered expression of synaptic proteins-mediated cellular signalings, supporting persistent impacts of fetal iron deficiency on synaptic efficacy, which likely cause the cognitive dysfunction and neurobehavioral abnormalities. Importantly, the findings uncover previously unsuspected pathways, including neuronal nitric oxide synthase signaling, identifying additional mechanisms that may contribute to the long-term biobehavioral deficits. PMID:24089371

  6. Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

    SciTech Connect

    Krueger, Katharina Straub, Heidrun; Hirner, Alfred V.; Hippler, Joerg; Binding, Norbert; Musshoff, Ulrich

    2009-04-01

    Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krueger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Mu{beta}hoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krueger, K., Straub, H., Binding, N., Mu{beta}hoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krueger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Mu{beta}hoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA{sup V}) and monomethylarsonous acid (MMA{sup III}) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA{sup V} had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA{sup III} strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 {mu}mol/l (adult rats) and 25 {mu}mol/l (young rats) and LTP amplitudes at concentrations of 25 {mu}mol/l (adult rats) and 10 {mu}mol/l (young rats), respectively. In contrast, application of 1 {mu}mol/l MMA{sup III} led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at

  7. Perinatal choline treatment modifies the effects of a visuo-spatial attractive cue upon spatial memory in naive adult rats.

    PubMed

    Brandner, Catherine

    2002-02-22

    The improvement in memory functions by choline supplementation is hypothesized to be due to increased synthesis and release of acetylcholine in the brain. We have found previously that combined pre- and postnatal choline supplementation results in long-lasting facilitation of spatial memory in juvenile rats when training was conducted in presence of a local salient cue. The present work aims to analyze the effects of peri- and postnatal choline supplementation on spatial abilities of naive adult rats. Treated rats were trained in various cued procedures of the Morris navigation task of 5 months of age. The treatment had a specific effect of reducing the escape latency of the rats when the platform was at a fixed location in space and indicated by a suspended cue. This effect was associated with an improved spatial memory when the cue and the platform were removed. In this condition, the control rats showed impaired spatial discrimination following the removal of the target cue, most likely due to an overshadowing of the distant environmental cues. This impairment was not observed in the treated rats. Further training with the suspended cue at unpredictable places in the pool revealed longer escape latencies in the control than in the treated rats suggesting that this procedure induced a selective perturbation of the normal but not of the treated rats. A special probe trial with the cue at an irrelevant location and no escape platform revealed a significant bias of the control rats towards the cue, but in treated rats towards the uncued spatial escape position. This behavioral dissociation suggests that a salient cue associated with the target induces an alternative "non spatial" guidance strategy in normal rats, with the risk of overshadowing attention towards more distant spatial cues. As a consequence, the improved escape in the presence of the cue in the treated rats is associated with a stronger memory of the spatial position following disappearance of the cue

  8. Alzheimer's disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla).

    PubMed

    Perez, Sylvia E; Raghanti, Mary Ann; Hof, Patrick R; Kramer, Lynn; Ikonomovic, Milos D; Lacor, Pascale N; Erwin, Joseph M; Sherwood, Chet C; Mufson, Elliott J

    2013-12-15

    The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid beta protein (Aβ) plaques and neurofibrillary tangles (NFT). Aβ pathology is a common feature in the aged nonhuman primate brain, whereas NFT are found almost exclusively in humans. Few studies have examined AD-related pathology in great apes, which are the closest phylogenetic relatives of humans. In the present study, we examined Aβ and tau-like lesions in the neocortex and hippocampus of aged male and female western lowland gorillas using immunohistochemistry and histochemistry. Analysis revealed an age-related increase in Aβ-immunoreactive plaques and vasculature in the gorilla brain. Aβ plaques were more abundant in the neocortex and hippocampus of females, whereas Aβ-positive blood vessels were more widespread in male gorillas. Plaques were also Aβ40-, Aβ42-, and Aβ oligomer-immunoreactive, but only weakly thioflavine S- or 6-CN-PiB-positive in both sexes, indicative of the less fibrillar (diffuse) nature of Aβ plaques in gorillas. Although phosphorylated neurofilament immunostaining revealed a few dystrophic neurites and neurons, choline acetyltransferase-immunoreactive fibers were not dystrophic. Neurons stained for the tau marker Alz50 were found in the neocortex and hippocampus of gorillas at all ages. Occasional Alz50-, MC1-, and AT8-immunoreactive astrocyte and oligodendrocyte coiled bodies and neuritic clusters were seen in the neocortex and hippocampus of the oldest gorillas. This study demonstrates the spontaneous presence of both Aβ plaques and tau-like lesions in the neocortex and hippocampus in old male and female western lowland gorillas, placing this species at relevance in the context of AD research. PMID:23881733

  9. Locomotor activity changes in female adolescent and adult rats during repeated treatment with a cannabinoid or club drug.

    PubMed

    Wiley, Jenny L; Evans, Rhys L; Grainger, Darren B; Nicholson, Katherine L

    2011-01-01

    Adolescents and young adults of both sexes are the primary consumers of "club" drugs; yet, most of the mechanistic preclinical research in this area has been performed in adult male rodents. The purpose of this study was to evaluate the acute and repeated effects of drugs that are commonly abused by adolescents in female adolescent and adult rats in a rodent model of behavioral sensitization. During two five-day periods separated by a two-day break, rats were injected daily with saline or with one of the following drugs: cocaine (7 or 15 mg/kg), ketamine (3 or 10 mg/kg), 3,4-methylenedioxymethamphetamine (MDMA) (3, 10, or 30 mg/kg), or Δ(9)-tetrahydrocannabinol (THC) (0.03, 0.1, 0.3 or 1 mg/kg) and their locomotor activity was measured. Cocaine increased activity across days in both age groups. Whereas ketamine produced progressive increases in activity with repeated administration in rats of both ages, MDMA increased, and then decreased, activity in the chronic dosing regimen in female adolescents only. Tolerance to the initial stimulatory effects of low doses of THC was observed at both ages. The results with THC are similar to those obtained for male rats tested under identical conditions in a previous study; however, in contrast with the present results in females, male adolescent rats in the previous study failed to develop behavioral sensitization to ketamine. Together, these results suggest that age and sex strongly influence the progressive adaptive changes that occur with repeated administration of some, but not all, of these commonly abused substances. PMID:22180350

  10. Effects of hypothyroidism upon the granular layer of the dentate gyrus in male and female adult rats: a morphometric study.

    PubMed

    Madeira, M D; Cadete-Leite, A; Andrade, J P; Paula-Barbosa, M M

    1991-12-01

    The effects of hypothyroidism upon the structure of the central nervous system of adult rats are poorly understood in spite of evidence that the mature brain is vulnerable to this condition. Existing developmental studies show that the morphological changes induced by thyroid hormone deficiency are related to alterations in neurogenesis. We studied the granular layer of the dentate gyrus under different experimental conditions of hypothyroidism, because in rodents the neurogenesis of the granule cells continues during adulthood. The following groups of rats were analysed: 1) control; 2) hypothyroid from day 0 until day 180 (hypothyroid group); 3) hypothyroid until day 30 and henceforth maintained euthyroid (recovery group); and 4) hypothyroid since day 30 (adult hypothyroid group). Groups of 6 male rats and 6 female rats were analysed separately. The volume of the dentate gyrus granular layer and the numerical density of its neurons were evaluated, so we were able to estimate the total number of granule cells. Because in the experimental groups the volume of the granular layer and the numerical density of its neurons were reduced, the total number of granule cells was decreased. In the hypothyroid and recovery groups the alterations were identical and more striking than in the adult hypothyroid groups. The total number of granule cells displayed sexual differences in all groups studied except in the hypothyroid groups. The present results support the view that thyroid hormone deficiency interferes with the process of cell acquisition by reducing neuronal proliferation and that it also leads to increased cell death. These events underlie the irreversible morphological changes observed in the brain of hypothyroid rats, either during development or at maturity. The referred structural alterations are probably related to the functional deficits observed in this condition. PMID:1797872

  11. Rehabilitation of masticatory function improves the alveolar bone architecture of the mandible in adult rats.

    PubMed

    Mavropoulos, Anestis; Odman, Anna; Ammann, Patrick; Kiliaridis, Stavros

    2010-09-01

    hypofunctional group (p<0.05). Both alveolar height and width were significantly correlated with all micro-tomographic parameters under study. The rehabilitation of masticatory function led to a significant improvement of alveolar bone architecture in adult rats, although the negative effects of hypofunction were not totally reversed during the period under study. PMID:20601301

  12. Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring

    PubMed Central

    Wilson, Christina A.; Terry, Alvin V.

    2013-01-01

    Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the α7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

  13. Fetal programming of colon cancer in adult rats: correlations with altered neonatal trajectory, circulating IGF-I and IGFPBs, and testosterone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lifelong consumption of soy protein isolate (SPI) reduces the incidence of azoxymethane (AOM)-induced colon tumors in adult male Sprague-Dawley rats. We determined if a maternal SPI diet during pregnancy could protect against colon cancer in progeny. Four groups of male rats were used: a lifetime ...

  14. Leptin-dependent neurotoxicity via induction of apoptosis in adult rat neurogenic cells

    PubMed Central

    Segura, Stéphanie; Efthimiadi, Laurie; Porcher, Christophe; Courtes, Sandrine; Coronas, Valérie; Krantic, Slavica; Moyse, Emmanuel

    2015-01-01

    Adipocyte-derived hormone leptin has been recently implicated in the control of neuronal plasticity. To explore whether modulation of adult neurogenesis may contribute to leptin control of neuronal plasticity, we used the neurosphere assay of neural stem cells derived from the adult rat subventricular zone (SVZ). Endogenous expression of specific leptin receptor (ObRb) transcripts, as revealed by RT-PCR, is associated with activation of both ERK and STAT-3 pathways via phosphorylation of the critical ERK/STAT-3 amino acid residues upon addition of leptin to neurospheres. Furthermore, leptin triggered withdrawal of neural stem cells from the cell cycle as monitored by Ki67 labeling. This effect was blocked by pharmacological inhibition of ERK activation thus demonstrating that ERK mediates leptin effects on neural stem cell expansion. Leptin-dependent withdrawal of neural stem cells from the cell cycle was associated with increased apoptosis, as detected by TUNEL, which was preceded by cyclin D1 induction. Cyclin D1 was indeed extensively colocalized with TUNEL-positive, apoptotic nuclei. Cyclin-D1 silencing by specific shRNA prevented leptin-induced decrease of the cell number per neurosphere thus pointing to the causal relationship between leptin actions on apoptosis and cyclin D1 induction. Leptin target cells in SVZ neurospheres were identified by double TUNEL/phenotypic marker immunocytofluorescence as differentiating neurons mostly. The inhibition of neural stem cell expansion via ERK/cyclin D1-triggered apoptosis defines novel biological action of leptin which may be involved in adiposity-dependent neurotoxicity. PMID:26441523

  15. Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

    PubMed

    Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders. PMID:26383033

  16. All-Trans Retinoic Acid Induces Expression of a Novel Intergenic Long Noncoding RNA in Adult rat Primary Hippocampal Neurons.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-02-01

    Around 90% of the mammalian genome undergoes pervasive transcription into various types of small and long regulatory noncoding RNAs, whereas only ∼ 1.5% codes for proteins. Long noncoding RNAs (lncRNAs) constitute diverse classes of sense- and antisense transcripts that are abundantly expressed in the mammalian central nervous system (CNS) in cell type- and developmental stage-specific manners. They are implicated in brain development, differentiation, neuronal plasticity, and other cognitive functions. Mammalian brain requires the vitamin A metabolite all-trans retinoic acid (atRA) for its normal development, differentiation, and cell-fate determination. However, its role in adult brain function is less understood. Here, we report atRA-mediated transcriptional upregulation of endogenous expression of a novel long intergenic noncoding RNA-rat brain expressed (LINC-RBE) in cultured primary hippocampal neurons from adult rat. We have previously reported LINC-RBE as an intergenic, simple repeat sequence containing lncRNA highly expressed in the rat brain. This is a first-time report of involvement of atRA in transcriptional upregulation of lncRNA expression in rat hippocampal neurons. Therefore, it may be involved in regulation of brain function and disease. PMID:26572536

  17. Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury.

    PubMed

    Li, Dongpeng; Ma, Shanshan; Guo, Dewei; Cheng, Tian; Li, Hongwei; Tian, Yi; Li, Jianbin; Guan, Fangxia; Yang, Bo; Wang, Jian

    2016-10-01

    Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague-Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID:26886755

  18. Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat.

    PubMed

    Ibrahim, Marwa A A; Elbakry, Reda H; Bayomy, Naglaa A

    2016-02-01

    Bisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki-67, activated caspase-3 and estrogen receptor alpha (ER-α). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki-67 and caspase-3, but a non-significant increase in ER-α expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer. PMID:26877094

  19. Microarray analysis of thyroid hormone-induced changes in mRNA expression in the adult rat brain.

    PubMed

    Haas, Michael J; Mreyoud, Amjad; Fishman, Miriam; Mooradian, Arshag D

    2004-07-15

    To determine which genes in the adult rat brain are regulated by thyroid hormone (TH), we used microarrays to examine the effect of hyperthyroidism on neuron-specific gene expression. Four-month-old male Fisher 344 rats were rendered hyperthyroid by intraperitoneal injection of 3,5,3'-L-triiodothyronine (T3, 15 microg/100 g body weight) for 10 consecutive days. To minimize interindividual variability, pooled cerebral tissue RNA from four-control and five-hyperthyroid rats was hybridized in duplicates to the Affymetrix (Santa Clara, CA) U34N rat neurobiology microarray, which contains probes for 1224 neural-specific genes. Changes in gene expression were considered significant only if they were observed in both pair-wise comparisons as well as by Northern blot analysis. Hyperthyroidism was associated with modest changes in the expression of only 11 genes. The expression of the phosphodiesterase Enpp2, myelin oligodendrocyte glycoprotein (Mog), microtubule-associated protein 2 (MAP2), growth hormone (GH), Ca(2+)/calmodulin-dependent protein kinase beta-subunit (Camk2b), neuron-specific protein PEP-19 (Pcp4), a sodium-dependent neurotransmitter, and the myelin-associated glycoprotein (S-MAG) was significantly increased. Three genes were suppressed by hyperthyroidism, including the activity and neurotransmitter-induced early genes-1 and -7 (ANIA-1 and ANIA-7) and the guanine nucleotide-binding protein one (Gnb1). The present study underscores the paucity of TH responsive genes in adult cerebral tissue. PMID:15234464

  20. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring.

    PubMed

    O'Loan, Jonathan; Eyles, Darryl W; Kesby, James; Ko, Pauline; McGrath, John J; Burne, Thomas H J

    2007-04-01

    Developmental vitamin D (DVD) deficiency alters brain development and behaviour in the rat. The aim of this study was to vary levels of vitamin D deficiency during gestation and examine the effects on developmental milestones and behaviour in adult offspring. By manipulating the withdrawal and reintroduction of vitamin D in the diet of female Sprague-Dawley