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Sample records for adult rat central

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    PubMed

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding. PMID:26486933

  7. CENTRAL AND SYMPATHO-ADRENAL RESPONSES TO INSULIN IN ADULT AND NEONATAL RATS (JOURNAL VERSION)

    EPA Science Inventory

    In the mature rat, subcutaneous administration of insulin (0.02 IU/g body wt.) produced hypoglycemia and a profound activation of the sympatho-adrenal pathway, as indicated by a marked depletion of adrenal catecholamines. Cellular glucopenia caused by administration of 2-deoxyglu...

  8. Penetration of Treosulfan and its Active Monoepoxide Transformation Product into Central Nervous System of Juvenile and Young Adult Rats.

    PubMed

    Romański, Michał; Baumgart, Joachim; Böhm, Sonja; Główka, Franciszek K

    2015-12-01

    Treosulfan (TREO) is currently investigated as an alternative treatment of busulfan in conditioning before hematopoietic stem cell transplantation. The knowledge of the blood-brain barrier penetration of the drug is still scarce. In this paper, penetration of TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into the CNS was studied in juvenile (JR) and young adult rats (YAR) for the first time. CD rats of both sexes (n = 96) received an intravenous dose of TREO 500 mg/kg b.wt. Concentrations of TREO, S,S-EBDM, and S,S-DEB in rat plasma, brain, and cerebrospinal fluid (CSF, in YAR only) were determined by validated bioanalytical methods. Pharmacokinetic calculations were performed in WinNonlin using a noncompartmental analysis and statistical evaluation was done in Statistica software. In male JR, female JR, male YAR, and female YAR, the brain/plasma area under the curve (AUC) ratio for unbound TREO was 0.14, 0.17, 0.10, and 0.07 and for unbound S,S-EBDM, it was 0.52, 0.48, 0.28, and 0.22, respectively. The CSF/plasma AUC ratio in male and female YAR was 0.12 and 0.11 for TREO and 0.66 and 0.64 for S,S-EBDM, respectively. Elimination rate constants of TREO and S,S-EBDM in all the matrices were sex-independent with a tendency to be lower in the JR. No quantifiable levels of S,S-DEB were found in the studied samples. TREO and S,S-EBDM demonstrated poor and sex-independent penetration into CNS. However, the brain exposure was greater in juvenile rats, so very young children might potentially be more susceptible to high-dose TREO-related CNS exposure than young adults. PMID:26428246

  9. Central NPY-Y5 receptors activation plays a major role in fasting-induced pituitary-thyroid axis suppression in adult rat.

    PubMed

    Costa-e-Sousa, Ricardo Henrique; Souza, Luana Lopes; Calviño, Camila; Cabanelas, Adriana; Almeida, Norma Aparecida Santos; Oliveira, Karen Jesus; Pazos-Moura, Carmen Cabanelas

    2011-11-10

    Neuropeptide Y (NPY) inhibits TRH neurons in fed state, and hypothalamic NPY higher expression during fasting has been proposed to be involved in fasting-induced suppression of the hypothalamus-pituitary-thyroid (HPT) axis. We investigated the role of central Y5 receptors in the control of thyrotropin (TSH) and thyroid hormone (TH) secretion. Fed and fasting rats received twice daily central injections (3rd ventricle) of Y5 receptor antagonist (CGP71683; 15nmol/rat) for 72h. Fasted rats also received a single central injection of CGP71683 (15nmol/rat) at the end of 72h of fasting. In fed rats, Y5 receptor blockade reduced total food intake by 32% and body mass by almost 10% (p<0.01), corroborating the role of this receptor in food intake control. 72h-fasted rats exhibited a 4-fold increase in serum TSH (p<0.001), 1h after a single injection of Y5 antagonist. Also with multiple injections during 72h of fasting, Y5 blockade resulted in activation of thyroid axis, as demonstrated by a 3-times rise in serum T4 (p<0.001), accompanied by unchanged TSH and T3. In fed rats, the chronic central administration of CGP71683 resulted in reduced total serum T4 without changes in free T4 and TSH. Serum leptin and PYY were not altered by the NPY central blockade in both fed and fasted rats, suggesting no role of these hormones in the alterations observed. Therefore, the inhibition of central Y5 neurotransmission resulted in activation of thyroid axis during fasting suggesting that NPY-Y5 receptors contribute to fasting-induced TSH and TH suppression. PMID:21771616

  10. Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats.

    PubMed

    Hsieh, Chih-Sung; Li, Shih-Wen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Su, Chung-Hao; Huang, Li-Tung

    2016-08-01

    Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain. PMID:27272689

  11. CENTRAL 5-ALPHA REDUCTION OF TESTOSTERONE IS REQUIRED FOR TESTOSTERONE’S INHIBITION OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS RESPONSE TO RESTRAINT STRESS IN ADULT MALE RATS

    PubMed Central

    Handa, Robert J.; Kudwa, Andrea E.; Donner, Nina C.; McGivern, Robert F.; Brown, Roger

    2013-01-01

    In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a precise regulatory mechanism that is influenced by circulating gonadal and adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement returns the response to that of the intact male. Testosterone (T) actions in regulating HPA activity may be through aromatization to estradiol, or by 5α-reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if the latter pathway is involved, we assessed the function of the HPA axis response to restraint stress following hormone treatments, or after peripheral or central treatment with the 5α-reductase inhibitor, finasteride. Initially, we examined the timecourse whereby gonadectomy alters the CORT response to restraint stress. Enhanced CORT responses were evident within 48hrs following gonadectomy. Correspondingly, treatment of intact male rats with the 5α-reductase inhibitor, finasteride, for 48 hrs, enhanced the CORT and ACTH response to restraint stress. Peripheral injections of gonadectomized male rats with DHT or T for 48 hrs reduced the ACTH and CORT response to restraint stress. The effects of T, but not DHT, could be blocked by the third ventricle administration of finasteride prior to stress application. These data indicate that the actions of T in modulating HPA axis activity involve 5α-reductase within the central nervous system. These results further our understanding of how T acts to modulate the neuroendocrine stress responses and indicate that 5α reduction to DHT is a necessary step for T action. PMID:23880372

  12. Central 5-alpha reduction of testosterone is required for testosterone's inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress in adult male rats.

    PubMed

    Handa, Robert J; Kudwa, Andrea E; Donner, Nina C; McGivern, Robert F; Brown, Roger

    2013-09-01

    In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a precise regulatory mechanism that is influenced by circulating gonadal and adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement returns the response to that of the intact male. Testosterone (T) actions in regulating HPA activity may be through aromatization to estradiol, or by 5α-reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if the latter pathway is involved, we assessed the function of the HPA axis response to restraint stress following hormone treatments, or after peripheral or central treatment with the 5α-reductase inhibitor, finasteride. Initially, we examined the timecourse whereby gonadectomy alters the CORT response to restraint stress. Enhanced CORT responses were evident within 48 h following gonadectomy. Correspondingly, treatment of intact male rats with the 5α-reductase inhibitor, finasteride, for 48 h, enhanced the CORT and ACTH response to restraint stress. Peripheral injections of gonadectomized male rats with DHT or T for 48 h reduced the ACTH and CORT response to restraint stress. The effects of T, but not DHT, could be blocked by the third ventricle administration of finasteride prior to stress application. These data indicate that the actions of T in modulating HPA axis activity involve 5α-reductase within the central nervous system. These results further our understanding of how T acts to modulate the neuroendocrine stress responses and indicate that 5α reduction to DHT is a necessary step for T action. PMID:23880372

  13. Long-term effects of early adolescent stress: dysregulation of hypothalamic-pituitary-adrenal axis and central corticotropin releasing factor receptor 1 expression in adult male rats.

    PubMed

    Li, Chuting; Liu, Yuan; Yin, Shiping; Lu, Cuiyan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2015-07-15

    Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. Studies have found that exposure to early stressful events is a risk factor for developing PTSD. However, a limited number of studies have explored the effects of traumatic stress in early adolescence on behavior, hypothalamic-pituitary-adrenal (HPA) axis function, central corticotropin releasing factor receptor 1 (CRFR1) expression and the relative vulnerability of PTSD in adulthood. The current study aims to explore these issues using inescapable electric foot shock to induce a PTSD model in early adolescent rats. Meanwhile, running on a treadmill for six weeks and administration of the antagonist with 3.2mg/kg/day of CP-154, 526 for 14 consecutive days were used as therapeutic measures. Presently, the stress (S) group showed more anxiety and depression in the open field (OF) test and elevated plus maze (EPM) test, memory damage in the Y maze test, decreased basal CORT level, increased DEX negative feedback inhibition and exacerbated and longer-lasting reaction to CRH challenge in the DEX/CRH test compared with the control group. Central CRFR1 expression was also changed in the S group, as evidenced by the increased CRFR1 expression in the hypothalamus, amygdala and the prefrontal cortex (PFC). However, treadmill exercise alleviated early adolescent stress-induced behavior abnormalities and improved the functional state of the HPA axis, performing a more powerful effect than the CRFR1 antagonist CP-154, 526. Additionally, this study revealed that the alteration of central CRFR1 expression might play an important role in etiology of PTSD in adulthood. PMID:25882722

  14. Central auditory conduction time in the rat.

    PubMed

    Shaw, N A

    1990-01-01

    Central conduction time is the time for an afferent volley to traverse the central pathways of a sensory system. In the present study, central auditory conduction time (CACT) was calculated for the rat, the first such formal measurement in any animal. Brainstem auditory evoked potentials (BAEPs) were recorded simultaneously with the primary response of the auditory cortex (P1). The latency of wave II of the BAEP, which arises in the cochlear nucleus, was subtracted from that of P1. This yielded a mean CACT of 6.6 ms. The results confirm a previous theoretical estimate that CACT in the rat is at least twice as long as central somatosensory conduction time. PMID:2311700

  15. Monoclonal antibodies to a rat nestin fusion protein recognize a 220-kDa polypeptide in subsets of fetal and adult human central nervous system neurons and in primitive neuroectodermal tumor cells.

    PubMed Central

    Tohyama, T.; Lee, V. M.; Rorke, L. B.; Marvin, M.; McKay, R. D.; Trojanowski, J. Q.

    1993-01-01

    Nestin is the major intermediate filament protein of embryonic central nervous system (CNS) progenitor cells. To identify proteins involved in early stages of lineage commitment in the developing human CNS we generated monoclonal antibodies to a TrpE-rat nestin fusion protein. This resulted in a monoclonal antibody (designated NST11) that did not recognize authentic human nestin, but did recognize a novel neuron-specific human polypeptide expressed in a subset of embryonic and adult CNS neurons as well as in medulloblastomas. NST11 immunoreactivity was abundant in developing spinal cord motor neurons, but was extinguished in these neurons by 17 weeks gestation. NST11 also labeled Purkinje cells at 17 weeks gestation, but Purkinje cells continued to express the NST11 antigen throughout gestation as well as in the adult cerebellum, and NST11 immunoreactivity was more abundant in Purkinje cells than in any other human CNS neurons. No NST11 immunoreactivity was detected in cells of the adult human peripheral nervous system or in a variety of adult non-neural human tissues. Further, NST11 almost exclusively stained cerebellar medulloblastomas. In Western blots of immature and mature human cerebral and cerebellar extracts, NST11 did not bind human nestin, but did detect an immunoband with a molecular weight of 220 kd. A similar immunoband was detected in medulloblastoma-derived cell lines with a neuron-like phenotype. These findings suggest that the NST11 monoclonal antibody recognizes a novel protein expressed by a subpopulation of immature and mature human CNS neurons, medulloblastomas, and medulloblastoma-derived cell lines. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7686344

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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...

  1. Overview of Central Auditory Processing Deficits in Older Adults.

    PubMed

    Atcherson, Samuel R; Nagaraj, Naveen K; Kennett, Sarah E W; Levisee, Meredith

    2015-08-01

    Although there are many reported age-related declines in the human body, the notion that a central auditory processing deficit exists in older adults has not always been clear. Hearing loss and both structural and functional central nervous system changes with advancing age are contributors to how we listen, hear, and process auditory information. Even older adults with normal or near normal hearing sensitivity may exhibit age-related central auditory processing deficits as measured behaviorally and/or electrophysiologically. The purpose of this article is to provide an overview of assessment and rehabilitative approaches for central auditory processing deficits in older adults. It is hoped that the outcome of the information presented here will help clinicians with older adult patients who do not exhibit the typical auditory processing behaviors exhibited by others at the same age and with comparable hearing sensitivity all in the absence of other health-related conditions. PMID:27516715

  2. Overview of Central Auditory Processing Deficits in Older Adults

    PubMed Central

    Atcherson, Samuel R.; Nagaraj, Naveen K.; Kennett, Sarah E.W.; Levisee, Meredith

    2015-01-01

    Although there are many reported age-related declines in the human body, the notion that a central auditory processing deficit exists in older adults has not always been clear. Hearing loss and both structural and functional central nervous system changes with advancing age are contributors to how we listen, hear, and process auditory information. Even older adults with normal or near normal hearing sensitivity may exhibit age-related central auditory processing deficits as measured behaviorally and/or electrophysiologically. The purpose of this article is to provide an overview of assessment and rehabilitative approaches for central auditory processing deficits in older adults. It is hoped that the outcome of the information presented here will help clinicians with older adult patients who do not exhibit the typical auditory processing behaviors exhibited by others at the same age and with comparable hearing sensitivity all in the absence of other health-related conditions. PMID:27516715

  3. 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,...

  4. Effects of aging on peripheral and central auditory processing in rats.

    PubMed

    Costa, Margarida; Lepore, Franco; Prévost, François; Guillemot, Jean-Paul

    2016-08-01

    Hearing loss is a hallmark sign in the elderly population. Decline in auditory perception provokes deficits in the ability to localize sound sources and reduces speech perception, particularly in noise. In addition to a loss of peripheral hearing sensitivity, changes in more complex central structures have also been demonstrated. Related to these, this study examines the auditory directional maps in the deep layers of the superior colliculus of the rat. Hence, anesthetized Sprague-Dawley adult (10 months) and aged (22 months) rats underwent distortion product of otoacoustic emissions (DPOAEs) to assess cochlear function. Then, auditory brainstem responses (ABRs) were assessed, followed by extracellular single-unit recordings to determine age-related effects on central auditory functions. DPOAE amplitude levels were decreased in aged rats although they were still present between 3.0 and 24.0 kHz. ABR level thresholds in aged rats were significantly elevated at an early (cochlear nucleus - wave II) stage in the auditory brainstem. In the superior colliculus, thresholds were increased and the tuning widths of the directional receptive fields were significantly wider. Moreover, no systematic directional spatial arrangement was present among the neurons of the aged rats, implying that the topographical organization of the auditory directional map was abolished. These results suggest that the deterioration of the auditory directional spatial map can, to some extent, be attributable to age-related dysfunction at more central, perceptual stages of auditory processing. PMID:27306460

  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. 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...

  7. Central action of phenylethylamine in rats.

    PubMed

    Jagiełło-Wójtowicz, E

    1981-01-01

    Phenylethylamine (PEA), 10, 50 and 100 microgram/rat ivc depressed the spontaneous and explorative motor activities, did not affect the body temperature and potentiated the action of hypnotics. The PEA-induced depression of motor activity was antagonized by spiperone, phenoxybenzamine, propranolol and, slightly, by alpha-MT. In rats with total chemical destruction of catecholamine neurons and in rats with selective lesion of dopamine neurons, PEA increased motor activity. Similar effect was observed after administration of reserpine, reserpine together with 6-hydroxydopamine and yohimbine. PEA potentiated the amphetamine and apomorphine stereotypy but inhibited amphetamine hypermotility: in the latter experiment slight periodical stereotyped head movements were observed. PEA did not affect haloperidol and fluphenazine induced catalepsy. It did not change the immobility period in the behavioral despair test. In doses of 0 . 1, 1 and 10 mg/kg iv it potentiated flexor reflex of the hind paw of the spinal rat. Phentolamine (10 mg/kg iv) and propranolol (5 mg/kg iv) slightly potentiated the stimulatory effect of PEA. In doses of 50 and 100 microgram ivc PEA did not affect the level and utilization of noradrenaline, and did not change the level of dopamine but depressed its utilization in the cerebral cortex, striatum and hippocampus. PMID:7196039

  8. Central Sensitization and MAPKs are Involved in Occlusal Interference-Induced Facial Pain in Rats

    PubMed Central

    Cao, Ye; Li, Kai; Fu, Kai-Yuan; Xie, Qiu-Fei; Chiang, Chen-Yu; Sessle, Barry J.

    2013-01-01

    We previously developed a rat dental occlusal interference model of facial pain that was produced by bonding a crown onto the right maxillary first molar and was reflected in sustained facial hypersensitivity that was suggestive of the involvement of central sensitization mechanisms. The aim of the present study was to investigate potential central mechanisms involved in the occlusal interference-induced facial hypersensitivity. A combination of behavioral, immunohistochemical, Western blot and electrophysiological recording procedures was used in 98 male adult Sprague-Dawley rats that either received the occlusal interference or were sham-operated or naive rats. Immunohistochemically labeled astrocytes and microglia in trigeminal subnucleus caudalis (Vc) showed morphological changes indicative of astrocyte and microglial activation after the occlusal interference. Prolonged upregulation of p38 MAPK and ERK was also documented in Vc after placement of the occlusal interference, and was expressed in both neurons and glial cells at time points when rats showed peak mechanical facial hypersensitivity. The i.t. administration of the p38 MAPK inhibitor SB203580 to the medulla significantly inhibited the occlusal interference-induced hypersensitivity, and the ERK inhibitor PD98059 produced an even stronger effect. Central sensitization of functionally identified Vc nociceptive neurons following placement of the occlusal interference was also documented by extracellular electrophysiological recordings, and i.t. administration of PD98059 could reverse the neuronal central sensitization. These novel findings suggest that central mechanisms including central sensitization of trigeminal nociceptive neurons and non-neuronal processes involving MAPKs play significant roles in the production of occlusal interference-induced facial pain. Perspective Central mechanisms including trigeminal nociceptive neuronal sensitization, non-neuronal processes involving glial activation and

  9. 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

  10. Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats.

    PubMed

    Cordeiro, L M S; Guimarães, J B; Wanner, S P; La Guardia, R B; Miranda, R M; Marubayashi, U; Soares, D D

    2014-02-01

    Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p-CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p-CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 μM) and underwent a submaximal exercise test until fatigue. Icv TRP-treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p-CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p-CPA administration accelerated cutaneous heat dissipation when compared with saline-pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p-CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise. PMID:22540893

  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. Central cholinergic control of vasopressin release in conscious rats

    SciTech Connect

    Iitake, K.; Share, L.; Ouchi, Y.; Crofton, J.T.; Brooks, D.P.

    1986-08-01

    Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 g icv), but not by the nicotinic blocker, hexamethonium (10 g icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and they very small elevation in the plasma vasopressin concentration induced by nicotine (10 g icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat.

  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

    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 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

  16. 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

  17. 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...

  18. Centrally administered glucagon stimulates sympathetic nerve activity in rat.

    PubMed

    Krzeski, R; Czyzyk-Krzeska, M F; Trzebski, A; Millhorn, D E

    1989-12-18

    The effect of pancreatic glucagon given intravenously, intracerebroventricularly and microinjected into the nucleus of the solitary tract on sympathetic activity in the cervical trunk and adrenal nerve was examined in rat. In each case glucagon caused a relatively long-lasting substantial increase in discharge of both nerves. This finding shows that glucagon can act centrally to stimulate sympathetic activity. The most probable site for the sympathoexcitatory effect of glucagon is the nucleus of the solitary tract. PMID:2598031

  19. Central myelin gene expression during postnatal development in rats exposed to nicotine gestationally.

    PubMed

    Cao, Junran; Dwyer, Jennifer B; Gautier, Nicole M; Leslie, Frances M; Li, Ming D

    2013-10-11

    Abnormal myelin gene expression in the central nervous system (CNS) is associated with many mental illnesses, including psychiatric disorders and drug addiction. We have previously shown that prenatal exposure to nicotine, the major psychoactive component in cigarette smoke, alters myelin gene expression in the CNS of adolescent rats. To examine whether this effect is specific for adolescents, we examined myelin gene expression in the CNS of juveniles and adults. Pregnant Sprague-Dawley rats were treated with nicotine (3 mg/kg/day; GN) or saline (GS) via osmotic mini pumps from gestational days 4-18. Both male and female offspring were sacrificed at postnatal day P20-21 (juveniles), P35-36 (adolescents), or P59-60 (adults). Three limbic brain regions, the prefrontal cortex (PFC), caudate putamen (CPu), and nucleus accumbens (NAc), were dissected. The expression of genes encoding major myelin components was evaluated using quantitative RT-PCR. We found that GN altered myelin gene expression in juveniles with brain region and sex differences. The pattern of alteration was different from that observed in adolescents. Although these genes were expressed normally in male adults, we observed decreased expression in GN-treated female adults, especially in the CPu. Thus, GN altered myelin gene expression throughout postnatal development and adulthood. The effect on adolescents was quite different from that at other ages, which correlated with the unique symptoms of many psychiatric disorders during adolescence. PMID:23962570

  20. 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

  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. 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

  3. 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

  4. 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

  5. Propylene oxide causes central-peripheral distal axonopathy in rats

    SciTech Connect

    Ohnishi, A.; Yamamoto, T.; Murai, Y.; Hayashida, Y.; Hori, H.; Tanaka, I.

    1988-09-01

    In Wistar rats subjected daily to a 6-hr exposure of propylene oxide (PO) at a concentration of 1,500 ppm (5 times a wk for 7 wk), ataxia developed in the hindlegs. Myelinated fibers in hindleg nerves and in the fasciculus gracilis showed axonal degeneration, sparing the nerve cell body of the first sacral dorsal root ganglion and myelinated fibers of the first sacral dorsal and ventral roots. These pathologic findings are compatible with central-peripheral distal axonopathy. This is apparently the first animal model of PO neuropathy to be verified histologically.

  6. Modeling the Nonlinear Motion of the Rat Central Airways.

    PubMed

    Ibrahim, G; Rona, A; Hainsworth, S V

    2016-01-01

    Advances in volumetric medical imaging techniques allowed the subject-specific modeling of the bronchial flow through the first few generations of the central airways using computational fluid dynamics (CFD). However, a reliable CFD prediction of the bronchial flow requires modeling of the inhomogeneous deformation of the central airways during breathing. This paper addresses this issue by introducing two models of the central airways motion. The first model utilizes a node-to-node mapping between the discretized geometries of the central airways generated from a number of successive computed tomography (CT) images acquired dynamically (without breath hold) over the breathing cycle of two Sprague-Dawley rats. The second model uses a node-to-node mapping between only two discretized airway geometries generated from the CT images acquired at end-exhale and at end-inhale along with the ventilator measurement of the lung volume change. The advantage of this second model is that it uses just one pair of CT images, which more readily complies with the radiation dosage restrictions for humans. Three-dimensional computer aided design geometries of the central airways generated from the dynamic-CT images were used as benchmarks to validate the output from the two models at sampled time-points over the breathing cycle. The central airway geometries deformed by the first model showed good agreement to the benchmark geometries within a tolerance of 4%. The central airway geometry deformed by the second model better approximated the benchmark geometries than previous approaches that used a linear or harmonic motion model. PMID:26592166

  7. 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

  8. 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.

  9. Central nervous system vasculitis in adults and children.

    PubMed

    Twilt, Marinka; Benseler, Susanne M

    2016-01-01

    Primary angiitis of the central nervous system (PACNS) is an inflammatory brain disease targeting the cerebral blood vessels, leading to a wide spectrum of signs and symptoms, including neurologic deficits, cognitive dysfunction, and psychiatric symptoms. The inflammation could be reversible if diagnosed and treated early. The diagnosis requires the careful consideration and rapid evaluation of systemic underlying conditions and disease mimics. The differential diagnosis is distinctly different for angiography-positive and -negative PACNS subtypes and differs depending on age, so there is childhood PACNS or adult PACNS. Distinct disease subtypes have been described, with characteristic disease course, neuroimaging findings, and histopathologic features. Novel and traditional biomarkers, including von Willebrand factor antigen and cytokine levels, can help diagnose, and define subtype and disease activity. Treatment of PACNS should be tailored to the disease subtypes and clinical symptoms. Beyond immunosuppression it should include medications to control symptoms in order to support and enhance the child's or adult's ability to actively participate in rehabilitation. The mortality of PACNS has decreased; studies determining the morbidity and its determinants are urgently needed. PMID:27112683

  10. 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

  11. 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

  12. Evaluation of Central Auditory Discrimination Abilities in Older Adults

    PubMed Central

    Freigang, Claudia; Schmidt, Lucas; Wagner, Jan; Eckardt, Rahel; Steinhagen-Thiessen, Elisabeth; Ernst, Arne; Rübsamen, Rudolf

    2011-01-01

    The present study focuses on auditory discrimination abilities in older adults aged 65–89 years. We applied the “Leipzig inventory for patient psychoacoustic” (LIPP), a psychoacoustic test battery specifically designed to identify deficits in central auditory processing. These tests quantify the just noticeable differences (JND) for the three basic acoustic parameters (i.e., frequency, intensity, and signal duration). Three different test modes [monaural, dichotic signal/noise (s/n) and interaural] were used, stimulus level was 35 dB sensation level. The tests are designed as three-alternative forced-choice procedure with a maximum-likelihood procedure estimating p = 0.5 correct response value. These procedures have proven to be highly efficient and provide a reliable outcome. The measurements yielded significant age-dependent deteriorations in the ability to discriminate single acoustic features pointing to progressive impairments in central auditory processing. The degree of deterioration was correlated to the different acoustic features and to the test modes. Most prominent, interaural frequency and signal duration discrimination at low test frequencies was elevated which indicates a deterioration of time- and phase-dependent processing at brain stem and cortical levels. LIPP proves to be an effective tool to identify basic pathophysiological mechanisms and the source of a specific impairment in auditory processing of the elderly. PMID:21577251

  13. 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

  14. 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

  15. 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

  16. 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

  17. Residential Pesticide Usage in Older Adults Residing in Central California

    PubMed Central

    Armes, Mary N.; Liew, Zeyan; Wang, Anthony; Wu, Xiangmei; Bennett, Deborah H.; Hertz-Picciotto, Irva; Ritz, Beate

    2011-01-01

    Information on residential pesticide usage and behaviors that may influence pesticide exposure was collected in three population-based studies of older adults residing in the three Central California counties of Fresno, Kern, and Tulare. We present data from participants in the Study of Use of Products and Exposure Related Behaviors (SUPERB) study (N = 153) and from community controls ascertained in two Parkinson’s disease studies, the Parkinson’s Environment and Gene (PEG) study (N = 359) and The Center for Gene-Environment Studies in Parkinson’s Disease (CGEP; N = 297). All participants were interviewed by telephone to obtain information on recent and lifetime indoor and outdoor residential pesticide use. Interviews ascertained type of product used, frequency of use, and behaviors that may influence exposure to pesticides during and after application. Well over half of all participants reported ever using indoor and outdoor pesticides; yet frequency of pesticide use was relatively low, and appeared to increase slightly with age. Few participants engaged in behaviors to protect themselves or family members and limit exposure to pesticides during and after treatment, such as ventilating and cleaning treated areas, or using protective equipment during application. Our findings on frequency of use over lifetime and exposure related behaviors will inform future efforts to develop population pesticide exposure models and risk assessment. PMID:21909294

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. 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...

  3. 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

  4. 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

  5. Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats.

    PubMed

    D'Agostino, Dominic P; Pilla, Raffaele; Held, Heather E; Landon, Carol S; Puchowicz, Michelle; Brunengraber, Henri; Ari, Csilla; Arnold, Patrick; Dean, Jay B

    2013-05-15

    Central nervous system oxygen toxicity (CNS-OT) seizures occur with little or no warning, and no effective mitigation strategy has been identified. Ketogenic diets (KD) elevate blood ketones and have successfully treated drug-resistant epilepsy. We hypothesized that a ketone ester given orally as R,S-1,3-butanediol acetoacetate diester (BD-AcAc(2)) would delay CNS-OT seizures in rats breathing hyperbaric oxygen (HBO(2)). Adult male rats (n = 60) were implanted with radiotelemetry units to measure electroencephalogram (EEG). One week postsurgery, rats were administered a single oral dose of BD-AcAc(2), 1,3-butanediol (BD), or water 30 min before being placed into a hyperbaric chamber and pressurized to 5 atmospheres absolute (ATA) O2. Latency to seizure (LS) was measured from the time maximum pressure was reached until the onset of increased EEG activity and tonic-clonic contractions. Blood was drawn at room pressure from an arterial catheter in an additional 18 animals that were administered the same compounds, and levels of glucose, pH, Po(2), Pco(2), β-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone were analyzed. BD-AcAc(2) caused a rapid (30 min) and sustained (>4 h) elevation of BHB (>3 mM) and AcAc (>3 mM), which exceeded values reported with a KD or starvation. BD-AcAc(2) increased LS by 574 ± 116% compared with control (water) and was due to the effect of AcAc and acetone but not BHB. BD produced ketosis in rats by elevating BHB (>5 mM), but AcAc and acetone remained low or undetectable. BD did not increase LS. In conclusion, acute oral administration of BD-AcAc(2) produced sustained ketosis and significantly delayed CNS-OT seizures by elevating AcAc and acetone. PMID:23552496

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Female rats are more susceptible to central nervous system oxygen toxicity than male rats

    PubMed Central

    Held, Heather E.; Pilla, Raffaele; Ciarlone, Geoffrey E.; Landon, Carol S.; Dean, Jay B.

    2014-01-01

    Abstract Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS‐OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS‐OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio‐telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (−42, −49, and −57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (−60, −86, and −73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (−0.4 ± 1.5 g) or FB (−1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS‐OT than males. PMID:24771690

  14. Female rats are more susceptible to central nervous system oxygen toxicity than male rats.

    PubMed

    Held, Heather E; Pilla, Raffaele; Ciarlone, Geoffrey E; Landon, Carol S; Dean, Jay B

    2014-01-01

    Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males. PMID:24771690

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

    PubMed Central

    Quagliotto, E.; Casali, K.R.; Dal Lago, P.; Rasia-Filho, A.A.

    2014-01-01

    The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP50, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV. PMID:25424367

  1. Theory of Mind and Central Coherence in Adults with High-Functioning Autism or Asperger Syndrome

    ERIC Educational Resources Information Center

    Beaumont, Renae; Newcombe, Peter

    2006-01-01

    The study investigated theory of mind and central coherence abilities in adults with high-functioning autism (HFA) or Asperger syndrome (AS) using naturalistic tasks. Twenty adults with HFA/AS correctly answered significantly fewer theory of mind questions than 20 controls on a forced-choice response task. On a narrative task, there were no…

  2. 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

  3. 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

  4. 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...

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. 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

  11. 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

  12. Comparison of Ultrasonography-Guided Central Venous Catheterization Between Adult and Pediatric Populations

    SciTech Connect

    Tercan, Fahri Oguzkurt, Levent; Ozkan, Ugur; Eker, Hatice Evren

    2008-05-15

    The purpose of this study was to compare the technical success and complication rates of ultrasonography-guided central venous catheterization between adult and pediatric patients which have not been reported previously. In a 4-year period, 859 ultrasonography-guided central vein catheterizations in 688 adult patients and 247 catheterizations in 156 pediatric patients were retrospectively evaluated. Mean age was 56.3 years (range, 18 to 95 years) for adults and 3.3 years (range, 0.1 to 16.3 years) for children. The preferred catheterization site was internal jugular vein in 97% of adults and 85% of children. The technical success rate, mean number of punctures, and rate of single wall puncture were 99.4%, 1.04 (range, 1-3), and 83% for adults and 90.3%, 1.25 (range, 1-5), and 49% for children, respectively. All the differences were statistically significant (p < 0.05). Complication rates were 2.3% and 2.4% for adults and children, respectively (p > 0.05). Major complications such as pneumothorax and hemothorax were not seen in any group. In conclusion, ultrasonography-guided central venous catheterization has a high technical success rate, lower puncture attempt rate, and higher single wall puncture rate in adults compared to children. Complication rates are comparable in the two groups.

  13. Comparison of ultrasonography-guided central venous catheterization between adult and pediatric populations.

    PubMed

    Tercan, Fahri; Oguzkurt, Levent; Ozkan, Ugur; Eker, Hatice Evren

    2008-01-01

    The purpose of this study was to compare the technical success and complication rates of ultrasonography-guided central venous catheterization between adult and pediatric patients which have not been reported previously. In a 4-year period, 859 ultrasonography-guided central vein catheterizations in 688 adult patients and 247 catheterizations in 156 pediatric patients were retrospectively evaluated. Mean age was 56.3 years (range, 18 to 95 years) for adults and 3.3 years (range, 0.1 to 16.3 years) for children. The preferred catheterization site was internal jugular vein in 97% of adults and 85% of children. The technical success rate, mean number of punctures, and rate of single wall puncture were 99.4%, 1.04 (range, 1-3), and 83% for adults and 90.3%, 1.25 (range, 1-5), and 49% for children, respectively. All the differences were statistically significant (p < 0.05). Complication rates were 2.3% and 2.4% for adults and children, respectively (p > 0.05). Major complications such as pneumothorax and hemothorax were not seen in any group. In conclusion, ultrasonography-guided central venous catheterization has a high technical success rate, lower puncture attempt rate, and higher single wall puncture rate in adults compared to children. Complication rates are comparable in the two groups. PMID:18330631

  14. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  15. 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

  16. 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

  17. Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats.

    PubMed

    Lian, Yuling; Zhao, Fangui; Wang, Wenjun

    2016-08-01

    Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats. PMID:27233601

  18. 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

  19. 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

  20. Contrasting regional Fos expression in adolescent and young adult rats following acute administration of the antidepressant paroxetine.

    PubMed

    Karanges, Emily A; Ramos, Linnet; Dampney, Bruno; Suraev, Anastasia S; Li, Kong M; McGregor, Iain S; Hunt, Glenn E

    2016-03-01

    Adolescents and adults may respond differently to antidepressants, with poorer efficacy and greater probability of adverse effects in adolescents. The mechanisms underlying this differential response are largely unknown, but likely relate to an interaction between the neural effects of antidepressants and brain development. We used Fos immunohistochemistry to examine regional differences in adolescent (postnatal day (PND) 28) and young adult (PND 56) male, Wistar rats given a single injection of the selective serotonin reuptake inhibitor paroxetine (10mg/kg). Paroxetine induced widespread Fos expression in both adolescent and young adult rats. Commonly affected areas include the bed nucleus of the stria terminalis (dorsolateral), medial preoptic area, paraventricular hypothalamic and thalamic nuclei and central nucleus of the amygdala. Fos expression was generally lower in adolescents with significantly greater Fos expression observed in young adults in the prelimbic cortex, supraoptic nucleus, basolateral amygdala, lateral parabrachial and Kölliker-Fuse nuclei. However, a small subset of regions showed greater adolescent Fos expression including the nucleus accumbens shell, lateral habenula and dorsal raphe. Paroxetine increased plasma corticosterone concentrations in young adults, but not adolescents. Plasma paroxetine levels were not significantly different between the age groups. These results indicate a different c-Fos signature of acute paroxetine in adolescent rats, with greater activation in key mesolimbic and serotonergic regions, but a more subdued cortical, brainstem and hypothalamic response. This suggests that the atypical response of adolescents to paroxetine may be related to a blunted neuroendocrine response, combined with insufficient top-down regulation of limbic regions involved in reward and impulsivity. PMID:26876759

  1. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats

    PubMed Central

    Zhang, Zhenwen; Fang, Penghua; He, Biao; Guo, Lili; Runesson, Johan; Langel, Ülo; Shi, Mingyi; Zhu, Yan; Bo, Ping

    2016-01-01

    Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB)/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats. PMID:27127795

  2. Decreased stress responsivity of central and peripheral catecholaminergic systems in aged 344/N Fischer rats.

    PubMed Central

    Cizza, G; Pacak, K; Kvetnansky, R; Palkovits, M; Goldstein, D S; Brady, L S; Fukuhara, K; Bergamini, E; Kopin, I J; Blackman, M R

    1995-01-01

    We investigated the effects of stress on central and peripheral sympatho-adrenal and sympatho-neural functions in healthy, intact young (3-4 mo) and aged (24 mo) male Fischer 344/N rats. Extracellular fluid (ECF) levels of the catecholamines norepinephrine (NE), dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and dihydroxyphenylacetic acid (DOPAC) were obtained by microdialysis in the paraventricular nucleus (PVN) of the hypothalamus at baseline and during immobilization (IMMO). The baseline levels of these substances were similar in both age groups, and their concentrations increased significantly in response to IMMO. The IMMO-induced increases of NE and MHPG, however, were significantly smaller in old than in young rats. Plasma levels of the catecholamines NE, DHPG, MHPG, DOPAC, dihydroxyphenylalanine (DOPA), epinephrine (EPI), dopamine (DA), and HVA were also determined in young and old rats during IMMO. Basal levels of these substances were significantly higher in old than in young rats. The magnitude of the IMMO-induced increases in the majority of these compounds however, was significantly smaller in old than in young rats. We conclude that, at the basal state, aging in the Fischer rat is associated with normal PVN ECF, but high plasma catecholamine levels; at stress state, however, old rats have substantially lesser activation of their central and peripheral catecholaminergic systems than young rats. Images PMID:7883970

  3. 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

  4. 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

  5. Cervical Pre-Phrenic Interneurons in the Normal and Lesioned Spinal Cord of the Adult Rat

    PubMed Central

    Lane, Michael A.; White, Todd E.; Coutts, Marcella A.; Jones, Alex L.; Sandhu, Milapjit S.; Bloom, David C.; Bolser, Donald C.; Yates, Bill J.; Fuller, David D.; Reier, Paul J.

    2008-01-01

    While monosynaptic bulbospinal projections to phrenic motoneurons have been extensively described, little is known about the organization of phrenic premotor neurons in the adult rat spinal cord. As interneurons may play an important role in normal breathing and recovery following spinal cord injury, the present study has used anterograde and transneuronal retrograde tracing to study their distribution and synaptic relations. Exclusive unilateral, first-order labeling of the phrenic motoneuron pool with pseudorabies virus demonstrated a substantial number of second-order, bilaterally-distributed cervical interneurons predominantly in the dorsal horn and around the central canal. Combined transneuronal and anterograde tracing revealed ventral respiratory column projections to pre-phrenic interneurons suggesting some propriospinal relays exist between medullary neurons and the phrenic nucleus. Dual-labeling studies with pseudorabies virus recombinants also showed pre-phrenic interneurons integrated with either contralateral phrenic or intercostal motoneuron pools. The stability of interneuronal pseudorabies virus labeling patterns following lateral cervical hemisection was then addressed. Except for fewer infected contralateral interneurons at the level of the central canal, the number and distribution of phrenic-associated interneurons was not significantly altered two weeks post-hemisection (i.e. when the earliest post-injury recovery of phrenic activity has been reported). These results demonstrate a heterogeneous population of phrenic-related interneurons. Their connectivity and relative stability after cervical hemisection raises speculation for potentially diverse roles in modulating phrenic function normally and post-injury. PMID:18924146

  6. The role of centrally injected nesfatin-1 on cardiovascular regulation in normotensive and hypotensive rats.

    PubMed

    Yilmaz, Mustafa Sertac; Altinbas, Burcin; Guvenc, Gokcen; Erkan, Leman Gizem; Avsar, Ozge; Savci, Vahide; Kucuksen, Duygu Udum; Arican, Ilker; Yalcin, Murat

    2015-12-01

    This study investigated the cardiovascular effects of nesfatin-1 in normotensive rats and animals subjected to hypotensive hemorrhage. Hemorrhagic hypotension was induced by withdrawal 2 mL blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP) and heart rate (HR). Intracerebroventricularly (i.c.v.) administered nesfatin-1 (100 pmol) increased MAP in both normotensive and hemorrhaged rats. Nesfatin-1 also caused bradycardia in normotensive and tachycardia in hemorrhaged rats. Centrally injected nesfatin-1 (100 pmol, i.c.v.) also increased plasma catecholamine, vasopressin and renin concentrations in control animals and potentiated the rise in all three cardiovascular mediators produced by hemorrhage. These findings indicate that centrally administered nesfatin-1 causes a pressor response in conscious normotensive and hemorrhaged rats and suggest that enhanced sympathetic activity and elevated vasopressin and renin concentrations mediate the cardiovascular effects of the peptide. PMID:26254710

  7. 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

  8. Preventive Effect of Central Administration of Venlafaxine on Morphine Physical Dependence, Nociception, and Blood Cortisol Level in Rat

    PubMed Central

    Motaghinejad, Majid; Ebrahimzadeh, Andia; Shabab, Behnaz

    2014-01-01

    Background: Chronic abuse of opiates induces dependency, but the neurobiological mechanisms of this event remain unclear. The aim of this study was to evaluate the effects of intracerebroventricular of venlafaxine on the morphine dependence and pain perception. Methods: A total of 80 adult male rats were divided into two major groups: (1) 40 of them was divided into groups of positive control (morphine dependent) negative control (received saline) and morphine dependent groups under treatment by central administration of venlafaxine at various dosages (25, 50, or 100 μg), after drug treatment total withdrawal index (TWI), latency time of withdrawal syndrome expression and blood cortisol as marker of anxiety were measured and compared with positive control and negative control. (2) Forty rats were grouped in control; indometacin treated (5 mg/kg) and grouped which received central administration of venlafaxine at three doses (25, 50, or 100 μg) and then pain perception and expression was assessed in the writhing test (acetic acid induced abdominal constriction), tail flick, and hot plate test. Results: Central administration of three doses (25, 50, or 100 μg,) of venlafaxine attenuates TWI to 47 ± 1.2, 38 ± 1.5, and 23 ± 1.1 and decrease blood cortisol level to 14 ± 1, 13.75 ± 0.5, and 12.5 ± 0.8, this decreases was significant in comparison with the positive control group (P < 0.05). Central administration of venlafaxine at mentioned doses significantly attenuates pain response with 37%, 24%, and 20% inhibition in writhing test, 69%, 34%, and 23% inhibition in hot plate test, and 29%, 23%, and 15% inhibition in tail flick test in comparison with control group (P < 0.05). Conclusions: This study suggested that central administration of venlafaxine attenuated morphine withdrawal index and can be effective in modulation of pain that was induced by morphine dependency. PMID:25538838

  9. Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury

    PubMed Central

    2009-01-01

    Background Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period. Results We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia (DRG), 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour. The results show a set of genes, differentially regulated in the adult DRG, that are principally involved in immune system modulation. A functional consequence of this different immune response to injury is that resident macrophages cluster around the large A sensory neuron bodies in the adult DRG seven days post injury, whereas the macrophages in young DRG remain scattered evenly throughout the ganglion, as in controls. Conclusions The results show, for the first time, a major difference in the neuroimmune response to nerve injury in the dorsal root ganglion of young and adult rats. Differential analysis reveals a new set of immune related genes in the ganglia, that are differentially regulated in adult neuropathic pain, and that are consistent with the selective activation of macrophages around adult, but not young large A sensory neurons post injury. These

  10. 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

  11. 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

  12. 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

  13. 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

  14. College and Adult Reading XI: The Eleventh Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    This yearbook contains selected papers presented at the twenty-third and twenty-fourth annual meetings of the North Central Reading Association, held in October of 1981 and 1982. Papers in the yearbook include: "History of Adult Reading Programs" (Clarence Anderson); "About Creativity and Study Skills" (Mark E. Thompson); "Recent Changes in…

  15. 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

  16. Gender-dependent behavioural impairment and brain metabolites in young adult rats after short term exposure to lead acetate.

    PubMed

    Mansouri, M T; Naghizadeh, B; López-Larrubia, P; Cauli, O

    2012-04-01

    We investigated the behavioural effects of short-term lead (Pb) exposure in adult rats producing blood Pb concentration (<10 μg/dL) below those associated with neurological impairment in occupationally exposed individuals. In order to assess gender differences, we performed parallel behavioural experiments in male and female rats. Exposure to Pb acetate (50 mg/L in drinking water) for 30-45 days induced behavioural alterations consisting in hyperactivity in a novel environment and impairment of spatial memory. These effects were observed only in male rats. Object recognition, motor coordination were unaffected by Pb exposure. Magnetic resonance spectroscopy allows in vivo assessment of main brain metabolites (glutamate/glutamine, creatine, myoinositol, N-acetylaspartate and choline) whose changes have been demonstrated in several central nervous system pathologies. Exposure to Pb did not affect metabolite profile in the striatum and increase myoinositol signal in the hippocampus of male rats. The increase in myoinositol in hippocampus suggests early Pb-induced alteration in glial metabolism in this brain region and may represent a potential marker of early brain dysfunction during Pb exposure. PMID:22285975

  17. 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

  18. Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in the Central Nervous System of Rats.

    PubMed

    Shi, Xing-Xing; Yin, Bai-Shuang; Yang, Peng; Chen, Hao; Li, Xin; Su, Li-Xue; Fan, Hong-Gang; Wang, Hong-Bin

    2016-01-01

    Xylazine is a potent analgesic extensively used in veterinary and animal experimentation. Evidence exists that the analgesic effect can be inhibited using adenosine 5'-monophosphate activated protein kinase (AMPK) inhibitors. Considering this idea, the aim of this study was to investigate whether the AMPK signaling pathway is involved in the central analgesic mechanism of xylazine in the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus and brainstem were collected for determination of liver kinase B1 (LKB1) and AMPKα mRNA expression using quantitative real-time polymerase chain reaction (qPCR), and phosphorylated LKB1 and AMPKα levels using western blot. The results of our study showed that compared with the control group, xylazine induced significant increases in AMPK activity in the cerebral cortex, hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01). Increased AMPK activities were accompanied with increased phosphorylation levels of LKB1 in corresponding regions of rats. The protein levels of phosphorylated LKB1 and AMPKα in these regions returned or tended to return to control group levels. However, in the brainstem, phosphorylated LKB1 and AMPKα protein levels were decreased by xylazine compared with the control (P < 0.05). In conclusion, our data indicates that xylazine alters the activities of LKB1 and AMPK in the central nervous system of rats, which suggests that xylazine affects the regulatory signaling pathway of the analgesic mechanism in the rat brain. PMID:27049320

  19. 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.

  20. 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

  1. Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats.

    PubMed

    Martínez, V; Taché, Y

    2001-03-01

    The CRF receptor subtype mediating the colonic and gastric motor responses to central CRF was investigated in conscious rats. CRF (0.6 microg/rat) injected intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated defecation (pellet/60 min: 4.1+/-1.0 and 8.7+/-0.7 respectively vs. 0.3+/-0.3 in i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-R1) antagonist, NBI-27914 (50-100 microg/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100 microg/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 microg/rat, i.c.v.) inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI-27914 injected i.c.v. at 100 microg/rat. Intracisternal (i.c.) injection of astressin (10 microg/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 microg) had no effect. These results indicate a differential role of central CRF receptor subtypes in the colonic stimulatory and gastric inhibitory motor responses to central CRF and that the CRF component of stress-related activation of colonic expulsion is primarily mediated by CRF-R1. PMID:11222989

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 5α-Reduced Neurosteroids Sex-Dependently Reverse Central Prenatal Programming of Neuroendocrine Stress Responses in Rats

    PubMed Central

    Donadio, Marcio V.; Yao, Song T.; Greenwood, Mike; Seckl, Jonathan R.; Murphy, David; Russell, John A.

    2015-01-01

    Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3β-androstanediol (3β-diol; 5α-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the “programmed” hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1β (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3β-diol normalized HPA axis responses to IL-1β in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5α-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5α-reductase and 3α-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1β. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5α-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner. PMID:25589761

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Gabapentin reverses central pain sensitization following a collagenase-induced intrathalamic hemorrhage in rats

    PubMed Central

    Castel, Aude; Vachon, Pascal

    2014-01-01

    Purpose The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP), amitriptyline (AMI), and carbamazepine (CARBA) for the treatment of a rodent central neuropathic pain model. Methods Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively) or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug). Results A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05). AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant. Conclusion Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA. PMID:24368890

  19. Effects of central administration of morphine on renal function in conscious rats.

    PubMed

    Danesh, S; Walker, L A

    1988-02-01

    Systemic administration of morphine in rats produces an anti-natriuretic effect that is at least partially dependent on renal nerves. The present studies were carried out in order to assess the renal response to central administration of morphine. Male Sprague-Dawley rats were surgically prepared with arterial, venous and bladder cannulas. In addition, a guide cannula was placed into the lateral ventrical and secured to the surface of the skull. Experiments were carried out at least 3 days after surgery. Renal clearance measurements were 30 min each. After a basal period, morphine sulfate (4 micrograms/4 microliters) or vehicle was injected into the lateral cerebral ventricle. Two clearance measurements were obtained, followed by central administration of naloxone HCl (4 micrograms/4 microliters) or vehicle and two more clearance periods. Morphine administration had no effect on blood pressure or heart rate but caused a sharp reduction in sodium excretion (3200 +/- 958 vs 970 +/- 158 nEq/100 g/min in period 5; P less than .05). This response was reversed by the addition of naloxone (3280 +/- 583 nEq/100 g/min in period 5; P less than .05). Furthermore, morphine had no effect on renal plasma flow and glomerular filtration rate. Naloxone increased the renal plasma flow and glomerular filtration rate in morphine-treated rats, whereas it had no effect in controls. It is concluded that central administration of morphine in conscious rats enhances renal tubular sodium reabsorption by an opiate receptor-dependent mechanism. PMID:3346840

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. National Economic Development Status May Affect the Association between Central Adiposity and Cognition in Older Adults

    PubMed Central

    Maharani, Asri; Tampubolon, Gindo

    2016-01-01

    Background Obesity is becoming a global problem, rather than one found only in developed countries. Although recent studies have suggested a detrimental effect of obesity on cognition, studies of the relationship between obesity and cognition among older adults have been limited to developed countries. We aimed to examine the associations between central obesity, as measured by waist circumference, and cognition level in adults aged 50 years and older in England and Indonesia. Methods We used linear regression models to analyse these associations and multiple imputation to manage missing data. The 2006 English Longitudinal Study of Ageing Wave 3 is the source of data from England, while data from Indonesia is sourced from the 2007 Indonesian Family Life Survey Wave 4. Findings Centrally obese respondents had lower cognition levels than non-centrally obese respondents in England. In contrast, central adiposity had a statistically significant positive association with cognition in Indonesia. Higher levels of education and higher economic status were associated with higher cognitive ability, while age was associated with lower cognition in both countries. Elevated C-reactive protein (CRP) concentrations and smoking behaviour, both linked to higher risk of obesity, were negatively associated with cognitive ability among older adults in England, but they had no statistically significant association with cognition among Indonesians. Interpretation The contradictory findings on obesity and cognition in England and Indonesia not only create a puzzle, but they may also have different policy implications in these countries. Reducing the prevalence of obesity may be the main focus in England and other developed countries to maintain older adults’ cognition. However, Indonesia and other developing countries should place more emphasis on education, in addition to continued efforts to tackle the double burden of malnutrition, in order to prevent cognitive impairment among

  6. 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

  7. 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

  8. 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

  9. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.

    PubMed

    Marques, Sueli; Zeisel, Amit; Codeluppi, Simone; van Bruggen, David; Mendanha Falcão, Ana; Xiao, Lin; Li, Huiliang; Häring, Martin; Hochgerner, Hannah; Romanov, Roman A; Gyllborg, Daniel; Muñoz-Manchado, Ana B; La Manno, Gioele; Lönnerberg, Peter; Floriddia, Elisa M; Rezayee, Fatemah; Ernfors, Patrik; Arenas, Ernest; Hjerling-Leffler, Jens; Harkany, Tibor; Richardson, William D; Linnarsson, Sten; Castelo-Branco, Gonçalo

    2016-06-10

    Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS. PMID:27284195

  10. 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...

  11. 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...

  12. 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…

  13. 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 ...

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. Using DNA barcoding to link cystacanths and adults of the acanthocephalan Polymorphus brevis in central Mexico.

    PubMed

    Alcántar-Escalera, F J; García-Varela, M; Vázquez-Domínguez, E; Pérez-Ponce de León, G

    2013-11-01

    In parasitic organisms, particularly helminths, the usage of the mitochondrial cytochrome c oxidase subunit I gene as the standard DNA barcoding region for species identification and discovery has been very limited. Here, we present an integrated study, based on both DNA barcoding and morphological analyses, for acanthocephalans belonging to the genus Polymorphus, whose larvae (cystacanths) are commonly found in the mesentery of freshwater fishes, while adults are found in the intestine of fish-eating birds. The alpha taxonomy of parasitic helminths is based on adult morphological traits, and because of that larval forms cannot be identified to species level based on morphology alone. DNA barcoding offers an alternative tool for linking larval stages of parasitic organisms to known adults. We sequenced cystacanths collected from freshwater fishes in localities across central Mexico and adults obtained from fish-eating birds, to determine whether they were conspecific. To corroborate the molecular results, we conducted a morphometric analysis with 'Proboscis profiler', which is a software tool developed to detect heterogeneity in morphologically similar acanthocephalans based on the multivariate statistical analysis of proboscis hook dimensions. Both sources of information indicate that cystacanths infecting freshwater fishes in central Mexico belong to a single species, Polymorphus brevis. PMID:23480472

  20. 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

  1. Effects of a ferment soy product on the adipocyte area reduction and dyslipidemia control in hypercholesterolemic adult male rats

    PubMed Central

    Cheik, Nadia Carla; Rossi, Elizeu Antônio; Guerra, Ricardo Luís Fernandes; Tenório, Neuli Maria; Oller do Nascimento, Cláudia Maria; Viana, Fabiana Pavan; Manzoni, Marla Simone Jovenasso; Carlos, Iracilda Zeponni; Leão da Silva, Patrícia; Vendramini, Regina Célia; Dâmaso, Ana Raimunda

    2008-01-01

    Background Available data on the effects of a fermented soy product enriched with Enterococcus faecium and Lactobacillus Jugurti on circulating lipids and adiposity are not completely settled. This study aimed to observe the effects of a fermented soy product enriched with Enterococcus faecium and Lactobacillus Jugurti on central obesity and dyslipidemia control in Wistar adult male rats. Methods Over a period of 8 weeks, animals had "ad libitum" food intake and water consumption as well as body weight and food consumption was monitored. The animals were assigned to four different experimental groups: Control Group (C); Control + Fermented Product Group (CPF); Hypercholesterolemic diet group (H); and Hypercholesterolemic + Fermented Product Group (HPF). The HPF and CPF groups received an intragastric administration of 1 ml of fermented product daily. After the experimental period the animals were killed by decapitation, blood was collected to measure cholesterol, triglycerides and HDL-cholesterol plasma concentration. Adipocyte circumference, lipolysis and lipogenis rates were measures using epididymal and retroperitoneal white adipose tissues. Results The results demonstrated that 1 ml/day/rat of the fermented soy product promoted important benefits such as reduced cholesterolemia in hypercholesterolemic diet group and the adipocyte circumference in both control and hypercholesterolemic diet group. Conclusion The fermented soy product enriched with Enterococcus faecium and Lactobacillus Jugurti decreased circulating lipids levels and reduced adipocyte area in rats. PMID:19087298

  2. Adolescent chronic stress causes hypothalamo-pituitary-adrenocortical hypo-responsiveness and depression-like behavior in adult female rats.

    PubMed

    Wulsin, Aynara C; Wick-Carlson, Dayna; Packard, Benjamin A; Morano, Rachel; Herman, James P

    2016-03-01

    Adolescence is a period of substantial neuroplasticity in stress regulatory neurocircuits. Chronic stress exposure during this period leads to long-lasting changes in neuroendocrine function and emotional behaviors, suggesting adolescence may be a critical period for development of stress vulnerability. This study investigated the effects of exposure to 14 days of chronic variable stress (CVS) in late-adolescent (pnd 45-58) female rats on neuroendocrine function, neuropeptide mRNA expression and depressive-like behavior in adolescence (pnd 59) and in adulthood (pnd 101). Adult females exposed to CVS in adolescence have a blunted hypothalamo-pituitary-adrenocortical (HPA) axis in response to a novel stressor and increased immobility in the forced swim test. Blunted HPA axis responses were accompanied by reduced vasopressin mRNA expression in the paraventricular nucleus of the hypothalamus (PVN), suggesting decreased central drive. Adolescent females tested immediately after CVS did not exhibit differences in stress reactivity or immobility in the forced swim test, despite evidence for enhanced central HPA axis drive (increased CRH mRNA expression in PVN). Overall, our study demonstrates that exposure to chronic stress in adolescence is sufficient to induce lasting changes in neuroendocrine drive and behavior, potentially altering the developmental trajectory of stress circuits as female rats age into adulthood. PMID:26751968

  3. Adolescent chronic stress causes hypothalamo-pituitary-adrenocortical hypo-responsiveness and depression-like behavior in adult female rats

    PubMed Central

    Wulsin, Aynara C.; Wick-Carlson, Dayna; Packard, Benjamin A.; Morano, Rachel; Herman, James P.

    2016-01-01

    Adolescence is a period of substantial neuroplasticity in stress regulatory neurocircuits. Chronic stress exposure during this period leads to long-lasting changes in neuroendocrine function and emotional behaviors, suggesting adolescence may be a critical period for development of stress vulnerability. This study investigated the effects of exposure to 14 days of chronic variable stress (CVS) in late-adolescent (pnd 45–58) female rats on neuroendocrine function, neuropeptide mRNA expression and depressive-like behavior in adolescence (pnd 59) and in adulthood (pnd 101). Adult females exposed to CVS in adolescence have a blunted hypothalamo-pituitary-adrenocortical (HPA) axis in response to a novel stressor and increased immobility in the forced swim test. Blunted HPA axis responses were accompanied by reduced vasopressin mRNA expression in the paraventricular nucleus of the hypothalamus (PVN), suggesting decreased central drive. Adolescent females tested immediately after CVS did not exhibit differences in stress reactivity or immobility in the forced swim test, despite evidence for enhanced central HPA axis drive (increased CRH mRNA expression in PVN). Overall, our study demonstrates that exposure to chronic stress in adolescence is sufficient to induce lasting changes in neuroendocrine drive and behavior, potentially altering the developmental trajectory of stress circuits as female rats age into adulthood. PMID:26751968

  4. 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

  5. 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…

  6. 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

  7. 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

  8. 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

  9. 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

  10. Influence of clitoria ternatea extracts on memory and central cholinergic activity in rats.

    PubMed

    Taranalli, A D; Cheeramkuzhy, T C

    2000-01-01

    Clitoria ternatea , commonly known as Shankpushpi, is widely used in the traditional Indian system of medicine as a brain tonic and is believed to promote memory and intelligence. We examined the effectiveness of alcoholic extracts of aerial and root parts of C. ternatea at 300 and 500 mg/kg doses orally in rats in attenuating electroshock-induced amnesia. Extracts at 300 mg/kg dose produced significant memory retention, and the root parts were found to be more effective. In order to delineate the possible mechanism through which C. ternatea elicits the anti-amnesic effects, we studied its influence on central cholinergic activity by estimating the acetylcholine content of the whole brain and acetylcholinesterase activity at different regions of the rat brain, viz., cerebral cortex, midbrain, medulla oblongata and cerebellum. Our results suggest that C. ternatea extracts increase rat brain acetylcholine content and acetyl cholinesterase a ctivity in a similar fashion to the standard cerebro protective drug Pyritinol. PMID:21214440

  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. Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in the Central Nervous System of Rats

    PubMed Central

    Shi, Xing-Xing; Yin, Bai-Shuang; Yang, Peng; Chen, Hao; Li, Xin; Su, Li-Xue; Fan, Hong-Gang; Wang, Hong-Bin

    2016-01-01

    Xylazine is a potent analgesic extensively used in veterinary and animal experimentation. Evidence exists that the analgesic effect can be inhibited using adenosine 5’-monophosphate activated protein kinase (AMPK) inhibitors. Considering this idea, the aim of this study was to investigate whether the AMPK signaling pathway is involved in the central analgesic mechanism of xylazine in the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus and brainstem were collected for determination of liver kinase B1 (LKB1) and AMPKα mRNA expression using quantitative real-time polymerase chain reaction (qPCR), and phosphorylated LKB1 and AMPKα levels using western blot. The results of our study showed that compared with the control group, xylazine induced significant increases in AMPK activity in the cerebral cortex, hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01). Increased AMPK activities were accompanied with increased phosphorylation levels of LKB1 in corresponding regions of rats. The protein levels of phosphorylated LKB1 and AMPKα in these regions returned or tended to return to control group levels. However, in the brainstem, phosphorylated LKB1 and AMPKα protein levels were decreased by xylazine compared with the control (P < 0.05). In conclusion, our data indicates that xylazine alters the activities of LKB1 and AMPK in the central nervous system of rats, which suggests that xylazine affects the regulatory signaling pathway of the analgesic mechanism in the rat brain. PMID:27049320

  14. 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.

  15. 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.

  16. 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

  17. Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats.

    PubMed

    Altinbas, Burcin; Yilmaz, Mustafa S; Savci, Vahide; Jochem, Jerzy; Yalcin, Murat

    2015-01-01

    Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats. PMID:25468497

  18. 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

  19. Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

    NASA Technical Reports Server (NTRS)

    Moffitt, J. A.; Schadt, J. C.; Hasser, E. M.

    1999-01-01

    The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

  20. 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

  1. Increasing trends in central obesity among Chinese adults with normal body mass index, 1993–2009

    PubMed Central

    2013-01-01

    Background Central obesity is thought to be more pathogenic than overall obesity and studies have shown that the association between waist circumference (WC) and mortality was strongest in those with a normal body mass index (BMI). The objective of our study was to determine secular trends in the prevalence of central obesity (WC ≥ 90 cm for men and ≥ 80 cm for women) among Chinese adults with normal BMI from 1993 to 2009 and to examine the impact of performance of combined BMI and WC on the prevalence of obesity in Chinese adults. Methods We used data from the China Health and Nutrition Survey (CHNS) conducted from 1993 to 2009. From which we included a total of 52023 participants aged ≥ 18 years. Results The age-standardized prevalence of central obesity among Chinese adults with BMI < 25 kg/m2 increased from 11.9% in 1993 to 21.1% in 2009 (P for linear trend <0.001). The upward trends were noted in both genders, all ages, rural/urban settings, and education groups (all P for linear trend <0.001), with greater increments in men, participants aged 18–64 years, and rural residents (P for interaction terms survey × sex, survey × age, and survey × rural/urban settings were 0.042, 0.003, and < 0.001, respectively). Trends in the prevalence of central obesity were similar when a more stringent BMI < 23 kg/m2 cut point (Asian cut point) was applied. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. More than 65% individuals with obesity would be missed if solely BMI was measured. Conclusions We observed an upward trend in the prevalence of central obesity among participants with normal BMI irrespective of sex, age, rural/urban settings, and education level. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. Approximately two thirds of the individuals with obesity would be missed if WC was not measured. It is, therefore, urgent to emphasize the importance of

  2. 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

  3. 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

  4. Neonatal finasteride administration alters hippocampal α4 and δ GABAAR subunits expression and behavioural responses to progesterone in adult rats.

    PubMed

    Modol, Laura; Casas, Caty; Navarro, Xavier; Llidó, Anna; Vallée, Monique; Pallarès, Marc; Darbra, Sònia

    2014-02-01

    Allopregnanolone is a neurosteroid that has been reported to fluctuate during early developmental stages. Previous experiments reported the importance of neonatal endogenous allopregnanolone levels for the maturation of the central nervous system and particularly for the hippocampus. Changes in neonatal allopregnanolone levels have been related to altered adult behaviour and with psychopathological susceptibility, including anxiety disorders, schizophrenia and drug abuse. However, the mechanism underlying these changes remains to be elucidated. In the present study we assessed changes in hippocampal expression of α4 and δ GABAA receptor (GABAAR) subunits as a consequence of neonatal finasteride (a 5-α reductase inhibitor) administration during early development (PD6 to PD15) in male rats. We observed that the treatment altered the temporal window of the natural peak in the expression of these subunits during development. Additionally, the level of these subunits were higher than in non-handled and control animals in the adult hippocampus. We observed that in adulthood, neonatal finasteride-treated animals presented an anxiogenic-like profile in response to progesterone administration which was absent in the rest of the groups. In conclusion, these results corroborate the relevance of neonatal maintenance of neurosteroid levels for behavioural anxiety responses in the adult, and point to some of the mechanisms involved in this alterations. PMID:24011224

  5. 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.

  6. Lesions of the central nucleus of the amygdala decrease taste threshold for sodium chloride in rats.

    PubMed

    Li, Jinrong; Yan, Jianqun; Chen, Ke; Lu, Bo; Wang, Qian; Yan, Wei; Zhao, Xiaolin

    2012-10-01

    Previous studies reported that NaCl intake was down-regulated in rats with bilateral lesions of the central nucleus of the amygdala (CeA). In line with the evidence from anatomical and physiological studies, such an inhibition could be the result of altered taste threshold for NaCl, one of the important factors in assessing taste functions. To assess the effect of CeA on the taste threshold for NaCl, a conditioned taste aversion (CTA) to a suprathreshold concentration of NaCl (0.1M) in rats with bilateral lesions of CeA or sham lesions was first established. And then, two-bottle choice tests between water and a series of concentrations of NaCl were conducted. The taste threshold for NaCl is defined as the lowest concentration at which there is a reliable difference scores between conditioned and control subjects. Rats with CeA lesions acquired a taste aversion for 0.1M NaCl when it was paired with LiCl and still retained the aversion after the two-bottle choice test. The results of the two-bottle choice test showed that the taste threshold for NaCl was 0.0006M in rats with CeA lesions, whereas in rats with sham lesions the threshold was 0.005M, which was identical to that of normal rats. The conditioned results confirm the claim that CeA is not essential in the profile of conditioned taste aversion. Our findings demonstrate that lesions of the CeA increased the sensitivity to NaCl taste in rats, indicating that the CeA may be involved in encoding the intensity of salty gustation elicited by NaCl. PMID:22796484

  7. Muscle Strength, Physical Activity, and Functional Limitations in Older Adults with Central Obesity

    PubMed Central

    Germain, Cassandra M.; Batsis, John A.; Vasquez, Elizabeth; McQuoid, Douglas R.

    2016-01-01

    Background. Obesity and muscle weakness are independently associated with increased risk of physical and functional impairment in older adults. It is unknown whether physical activity (PA) and muscle strength combined provide added protection against functional impairment. This study examines the association between muscle strength, PA, and functional outcomes in older adults with central obesity. Methods. Prevalence and odds of physical (PL), ADL, and IADL limitation were calculated for 6,388 community dwelling adults aged ≥ 60 with central obesity. Individuals were stratified by sex-specific hand grip tertiles and PA. Logistic models were adjusted for age, education, comorbidities, and body-mass index and weighted. Results. Overall prevalence of PL and ADL and IADL limitations were progressively lower by grip category. Within grip categories, prevalence was lower for individuals who were active than those who were inactive. Adjusted models showed significantly lower odds of PL OR 0.42 [0.31, 0.56]; ADL OR 0.60 [0.43, 0.84], and IADL OR 0.46 [0.35, 0.61] for those in the highest grip strength category as compared to those in the lowest grip category. Conclusion. Improving grip strength in obese elders who are not able to engage in traditional exercise is important for reducing odds of physical and functional impairment. PMID:27034833

  8. Adult multisystem langerhans cell histiocytosis presenting with central diabetes insipidus successfully treated with chemotherapy.

    PubMed

    Choi, Jung-Eun; Lee, Hae Ri; Ohn, Jung Hun; Moon, Min Kyong; Park, Juri; Lee, Seong Jin; Choi, Moon-Gi; Yoo, Hyung Joon; Kim, Jung Han; Hong, Eun-Gyoung

    2014-09-01

    We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated. PMID:25309800

  9. Adult Multisystem Langerhans Cell Histiocytosis Presenting with Central Diabetes Insipidus Successfully Treated with Chemotherapy

    PubMed Central

    Choi, Jung-Eun; Lee, Hae Ri; Ohn, Jung Hun; Moon, Min Kyong; Park, Juri; Lee, Seong Jin; Choi, Moon-Gi; Yoo, Hyung Joon; Kim, Jung Han

    2014-01-01

    We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated. PMID:25309800

  10. Effects of Acupuncture, RU-486 on the Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Adult Male Rats.

    PubMed

    Eshkevari, Ladan; Mulroney, Susan E; Egan, Rupert; Lao, Lixing

    2015-10-01

    We have recently reported that pretreatment with electroacupuncture (EA) at stomach meridian point 36 (St36) prevents the chronic cold-stress increase in the hypothalamus-pituitary-adrenal axis (HPA), an action that may be under central control. Given that treatment for stress-related symptoms usually begins after onset of the stress responses, the objectives of the present study were to determine the efficacy of EA St36 on HPA hormones when EA St36 is given after stress was initiated, if the results are long lasting, and if blocking the glucocorticoid receptor (GR) using RU-486 had the same effects as EA St36. Adult male rats were placed in 4 groups of animals, 3 of which were exposed to cold and 1 of which was a nontreatment control group. After exposure to the cold stress, 2 groups were treated with either EA St36 or sham-EA, repeated over 10 days. The increase in ACTH and corticosterone observed in stress-only rats was prevented in EA St36 animals, and the effects remained intact 4 days after withdrawal of EA but continuation of cold stress. When the GR was blocked with RU-486, the efficacy of EA St36 remained unchanged. GR blockade did significantly elevate ACTH, which is not seen with EA St36, suggesting that EA St36 does act centrally. The elevated HPA hormones in stress-only rats were associated with a significant increase in depressive and anxious behavior; this was not observed in the stressed EA St36 animals. The results indicate that EA specifically at St36 vs sham-EA is effective in treating chronic poststress exposure. PMID:26196540

  11. 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.

  12. 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.

  13. Lateral ventricle injection of orexin-A ameliorates central precocious puberty in rat via inhibiting the expression of MEG3

    PubMed Central

    Tao, Yue-Hong; Sharif, Nazir; Zeng, Bi-He; Cai, Yan-Yan; Guo, Yu-Xiu

    2015-01-01

    Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP. Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin. Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3. Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty. PMID:26722445

  14. 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

  15. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior. PMID:26321240

  16. Prevalence of Central Obesity among Adults with Normal BMI and Its Association with Metabolic Diseases in Northeast China

    PubMed Central

    Zhang, Peng; Wang, Rui; Gao, Chunshi; Jiang, Lingling; Lv, Xin; Song, Yuanyuan; Li, Bo

    2016-01-01

    Objectives The present study aimed to investigate the prevalence of central obesity among adults with normal BMI and its association with metabolic diseases in Jilin Province, China. Methods A population-based cross-sectional study was conducted in 2012 in Jilin Province of China. Information was collected by face to face interview. Descriptive data analysis and 95% confidence intervals (CI) of prevalence/frequency were conducted. Log-binomial regression analyses were used to find the independent factors associated with central obesity and to explore the adjusted association between central obesity and metabolic diseases among adults with normal BMI. Results Among the adult residents with normal BMI in Jilin Province, 55.6% of participants with central obesity self-assessed as normal weight and 27.0% thought their body weight were above normal. 12.7% of central obesity people took methods to lose weight, while 85.3% didn’t. Female, older people and non-manual worker had higher risk to be central obesity among adults with normal BMI. Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI, the PRs were 1.337 (1.224–1.461), 1.323 (1.193–1.456) and 1.261 (1.152–1.381) separately when adjusted for gender, age and BMI. Conclusions Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI in Jilin Province, China. The low rates of awareness and control of central obesity among adults with normal BMI should be improved by government and health department. PMID:27467819

  17. 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

  18. 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

  19. Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

    PubMed Central

    Badhan, Raj K. Singh; Chenel, Marylore; Penny, Jeffrey I.

    2014-01-01

    Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways. PMID:24647103

  20. Early social isolation provokes electrophysiological and structural changes in cutaneous sensory nerves of adult male rats.

    PubMed

    Segura, Bertha; Melo, Angel I; Fleming, Alison S; Mendoza-Garrido, Maria Eugenia; González del Pliego, Margarita; Aguirre-Benitez, Elsa L; Hernández-Falcón, Jesús; Jiménez-Estrada, Ismael

    2014-12-01

    Sensory and social deprivation from the mother and littermates during early life disturbs the development of the central nervous system, but little is known about its effect on the development of the peripheral nervous system. To assess peripheral effects of early isolation, male rat pups were reared artificially in complete social isolation (AR); reared artificially with two same-age conspecifics (AR-Social); or reared by their mothers and with littermates (MR). As adults, the electrophysiological properties of the sensory sural (SU) nerve were recorded. We found that the amplitude and normalized area (with respect to body weight) of the compound action potential (CAP) response provoked by single electrical pulses of graded intensity in the SU nerves of AR animals were shorter than the CAP recorded in SU nerves from MR and AR-Social animals. The slope of the stimulus-response curve of AR SU nerves was smaller than that of the other nerves. The histological characterization of axons in the SU nerves was made and showed that the myelin thickness of axons in AR SU nerves was significant lower (2-7µm) than that of the axons in the other nerves. Furthermore, the area and axon diameter of SU nerves of both AR and AR-Social animals were significant lower than in MR animals. This is the first report to show that maternal and littermate deprivation by AR disturbs the development of the myelination and electrophysiological properties of axons in the SU nerve; the replacement of social cues prevents most of the effects. PMID:24897933

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Comparing the Push-Pull Versus Discard Blood Sample Method From Adult Central Vascular Access Devices.

    PubMed

    Byrne, Dia

    2016-01-01

    This study demonstrates the feasibility of replacing the discard blood sampling method for central vascular access devices with the push-pull method. A comparative, within-subject design was used to evaluate 61 unique, paired blood samples from 1 adult outpatient oncology clinic. A 21-measure laboratory panel was conducted on each of the paired samples. Interpretation showed a small mean bias and excellent agreement between the methods. Blood samples obtained using the push-pull method were within clinically acceptable ranges. No hemolysis was noted by laboratory evaluation of 59 samples. PMID:27074989

  7. Lipid emulsion mitigates local anesthesia-induced central nervous system toxicity in rats

    PubMed Central

    WU, GANGMING; SUN, BIN; LIU, LI; ZHOU, JUN; MO, LIQUN; REN, CHANGHE; OU, CEHUA

    2015-01-01

    The aim of the present study was to investigate the effect of intravenously administered lipid emulsion on local anesthetic (LA)-induced central nervous system (CNS) toxicity. A total of 100 male Sprague Dawley rats were allocated at random into the following groups: Sham (A), lidocaine (B), levobupivacaine (C) and ropivacaine (D). Groups B–D were each subdivided into three subgroups: Toxic, post-conditioning and pre-conditioning. Intracerebroventricular injections of 0.9% normal saline (sham group) or LA were administered via microsyringe; in addition, a 20% lipid emulsion was injected into tail vein prior to the LA injection (pre-conditioning subgroups) or following rat respiratory arrest (post-conditioning subgroups). The heart rate, blood pressure, neurological behavior scores, neuronal density and time from LA injection to respiratory arrest, apnea and start of arrhythmia were measured. Rats in the toxic groups died due to respiratory arrest following the injection of LA into the lateral ventricle. Rats in the post-conditioning subgroups were resuscitated from the LA-induced respiratory arrest, while the pre-conditioning subgroup rats exhibited no respiratory arrest. No significant differences in heart rate were observed between the toxic and post-conditioning subgroups in the levobupivacaine and ropivacaine groups (P>0.05); however, a significant difference was observed between these treatment groups and the rats treated with lidocaine (P<0.01). A significant difference was also observed in the time from the LA injection to the onset of arrhythmia among the rats in groups B, C and D (P<0.01). No significant differences in the neurological behavior scores and neuronal density were observed in the hippocampal CA1 zone among group C and D rats in the post- and pre-conditioning subgroups at various time-points following treatment. Beyond that, the same phenomena regarding neurological behavior scores was observed in post- and pre-conditioning subgroups of group

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. A corrosive oesophageal burn model in rats: Double-lumen central venous catheter usage

    PubMed Central

    Bakan, Vedat; Çıralık, Harun; Kartal, Seyfi

    2015-01-01

    Background: We aimed to create a new and less invasive experimental corrosive oesophageal burn model using a catheter without a gastric puncture (gastrotomy). Materials and Methods: We conducted the study with two groups composed of 8 male rats. The experimental oesophageal burn was established by the application of 10% sodium hydroxide to the distal oesophagus under a pressure of 20 cmH2O, via 5-F double-lumen central venous catheter without a gastrotomy. The control group was given 0.9% sodium chloride. All rats were killed 24 h after administration of NaOH or 0.9% NaCl. Histologic damage to oesophageal tissue was scored by a single pathologist blind to groups. Results: The rats in the control group were observed to have no pathological changes. Corrosive oesophagitis (tissue congestion, oedema, inflammation, ulcer and necrosis) was observed in rats exposed to NaOH. Conclusion: We believe that an experimental corrosive oesophageal burn can safely be created under same hydrostatic pressure without a gastric puncture using this model. PMID:26712289

  15. A comparison of peripheral and central axotomy effects on neurofilament and tubulin gene expression in rat dorsal root ganglion neurons

    SciTech Connect

    Wong, J.; Oblinger, M.M. )

    1990-07-01

    The expression of major cytoskeletal protein mRNAs was studied in adult rat dorsal root ganglion (DRG) neurons after crushing either their central or peripheral branch axons. mRNA levels in DRG neurons were examined by quantitative in situ hybridization with radiolabeled cDNA probes specific for the low-molecular-weight neurofilament protein (NF-L) and beta-tubulin. The large-sized (greater than 1000 microns 2) neurons which give rise to myelinated axons in lumbar ganglia (L4 and L5) were studied 1 d through 8 weeks after either dorsal root or sciatic nerve crush. NF-L and beta-tubulin mRNA levels in axotomized DRG neurons were compared to those in contralateral control DRG neurons, as well as to those in normal (completely untreated) DRG cells. In the case of NF-L mRNA, changes were observed after central as well as peripheral branch axotomy and the time course and magnitude of changes were similar after both types of axotomy. NF-L mRNA levels initially decreased (first 2 weeks after crush) and then began to return towards control levels at longer survival times. Similar, but less pronounced, changes in NF-L mRNA levels also occurred in contralateral DRG neurons (which were uninjured); the changes in contralateral neurons were not simply a result of surgical stress since no changes in NF-L mRNA levels were observed in sham-operated DRG neurons. In the case of tubulin mRNA, changes were observed after central as well as peripheral branch axotomy by in situ hybridization, but the time course and magnitude of changes were different after each type of axotomy.

  16. 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

  17. 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 ...

  18. 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, ...

  19. 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,...

  20. The impact of two mild stressors on the nerve growth factor (NGF) immunoreactivity in the amygdala in aged rats compared to adult ones.

    PubMed

    Badowska-Szalewska, Ewa; Ludkiewicz, Beata; Krawczyk, Rafał; Moryś, Janusz

    2016-04-01

    Nerve growth factor (NGF) seems to play an important role in the ageing limbic system in response to stress. This study aimed to explore the influence of acute and chronic exposure to high-light open field (HL-OF) or forced swim (FS) stressors on the density of NGF immunoreactive (ir) neurons in the amygdala central (CeA), medial (MeA), lateral (LA) and basolateral (BLA) nuclei in adult (postnatal day 90; P90) and aged (P720) rats. In comparison with non-stressed rats, neither acute nor chronic HL-OF produced significant changes in the density of NGF-ir neurons of studied nuclei in P90 and P720 rats. However, not acute but chronic FS was the factor inducing an increase in the density of NGF-ir neurons in the CeA of both age groups and in the LA of P720 rats. Despite the lack of change in the density of NGF-ir neurons between P90 and P720 non-stressed rats, there were significant age-related changes in NGF-ir cells in FS and/or HL-OF stressed rats in all the tested nuclei, with the exception of the LA. It may be concluded that as far as the influence on NGF-ir cells in amygdaloid nuclei is concerned, HL-OF did not constitute an aggravating factor for rats in the ontogenetic periods studied. Moreover, upregulation of NGF-ir neurons predominantly in CeA after chronic FS seems to be neuroprotective. Age-dependent changes in the density of NGF-ir neurons in stressed rats are probably caused by ageing processes and they may point to dysregulation of excitatory control exerted by the amygdala. PMID:26724365

  1. Effects of a 60 Hz magnetic field on central cholinergic systems of the rat

    SciTech Connect

    Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W. )

    1993-03-15

    The authors studied the effects of an acute exposure to a 60 Hz magnetic field on sodium-dependent, high-affinity choline uptake in the brain of the rat. Decreases in uptake were observed in the frontal cortex and hippocampus after the animals were exposed to a magnetic field at flux densities [>=] 0.75 mT. These effects of the magnetic field were blocked by pretreating the animals with the narcotic antagonist naltrexone, but not by the peripheral opioid antagonist, naloxone methiodide. These data indicate that the magnetic-field-induced decreases in high-affinity choline uptake in the rat brain were mediated by endogenous opioids in the central nervous systems.

  2. Comparing the functional representations of central and border whiskers in rat primary somatosensory cortex.

    PubMed

    Brett-Green, B A; Chen-Bee, C H; Frostig, R D

    2001-12-15

    The anatomical representations of the large facial whiskers, termed barrels, are topographically organized and highly segregated in the posteromedial barrel subfield (PMBSF) of rat layer IV primary somatosensory cortex. Although the functional representations of single whiskers are aligned with their appropriate barrels, their areal extents are rather large, spreading outward from the appropriate barrel along the tangential plane and thereby spanning multiple neighboring and non-neighboring barrels and septal regions. To date, single-whisker functional representations have been characterized primarily for whiskers whose corresponding barrels are located centrally within the PMBSF (central whiskers). Using intrinsic signal imaging verified with post-imaging single-unit recording, we demonstrate that border whiskers, whose barrels are located at the borders of the PMBSF, also evoke large activity areas that are similar in size to those of central whiskers but spread beyond the PMBSF and sometimes beyond primary somatosensory cortex into the neighboring dysgranular zones. This study indicates that the large functional representation of a single whisker is a basic functional feature of the rat whisker-to-barrel system and, combined with results from other studies, suggest that a large functional representation of a small, point-like area on the sensory epithelium may be a functional feature of primary sensory cortex in general. PMID:11739601

  3. Central effects of camphor on GnRH and sexual hormones in male rat.

    PubMed

    Shahabi, Sima; Jorsaraei, Seyed Gholam Ali; Moghadamnia, Ali Akbar; Zabihi, Ebrahim; Aghajanpour, Seyed Mohsen; Mousavi Kani, Seyedeh Narges; Pourbagher, Roghieh; Hosseini, Seyed Ahmad; Esmaili, Mohsen; Yoonesi, Ali Asghar; Zarghami, Amin; Alinezhad, Farid

    2012-01-01

    In Persian traditional medicine is believed that camphor (a crystalline ketone obtained from cinnamomum camphora) is a suppressor of sexual behaviors. This study examined the central effects of camphor on sexual hormones (LH, FSH and testosterone) and GnRH plasma levels in male rat. Male Wistar rats weighing 250-260gr were selected and divided into control (no treatment), sham (ICV injection of EtOH 10%) and treatment (ICV injection of camphor in three doses 4, 20, 40 µg/ 10µl in alcohol) groups. The serum samples were used for assaying of GnRH, LH, FSH and testosterone. There were no significant differences in the levels of hormones between the groups of study. Despite the central administration of camphor in hypothalamus - pituitary - gonad (HPG) axis, no significant differences were seen in sex hormone`s levels compared to the control. With this finding, it can be concluded that camphor may not effectively handle the axis via central pathway. These data recommend further studies of camphor on the HPG axis. PMID:24551777

  4. Central Effects of Camphor on GnRH and Sexual Hormones in Male Rat

    PubMed Central

    Shahabi, Sima; Jorsaraei, Seyed Gholam Ali; Moghadamnia, Ali Akbar; Zabihi, Ebrahim; Aghajanpour, Seyed Mohsen; Mousavi Kani, Seyedeh Narges; Pourbagher, Roghieh; Hosseini, Seyed Ahmad; Esmaili, Mohsen; Yoonesi, Ali Asghar; Zarghami, Amin; Alinezhad, Farid

    2012-01-01

    In Persian traditional medicine is believed that camphor (a crystalline ketone obtained from cinnamomum camphora) is a suppressor of sexual behaviors. This study examined the central effects of camphor on sexual hormones (LH, FSH and testosterone) and GnRH plasma levels in male rat. Male Wistar rats weighing 250-260gr were selected and divided into control (no treatment), sham (ICV injection of EtOH 10%) and treatment (ICV injection of camphor in three doses 4, 20, 40 µg/ 10µl in alcohol) groups. The serum samples were used for assaying of GnRH, LH, FSH and testosterone. There were no significant differences in the levels of hormones between the groups of study. Despite the central administration of camphor in hypothalamus - pituitary - gonad (HPG) axis, no significant differences were seen in sex hormone`s levels compared to the control. With this finding, it can be concluded that camphor may not effectively handle the axis via central pathway. These data recommend further studies of camphor on the HPG axis. PMID:24551777

  5. 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

  6. 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

  7. 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

  8. Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

    PubMed Central

    Zarco, Natanael; Bautista, Elizabeth; Cuéllar, Manola; Vergara, Paula; Flores-Rodriguez, Paola; Aguilar-Roblero, Raúl

    2013-01-01

    Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS. PMID:23813868

  9. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults

    PubMed Central

    Yang, Chih-Hsiang; Maher, Jaclyn P.; Conroy, David E.

    2015-01-01

    Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October–November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID:26844135

  10. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults.

    PubMed

    Yang, Chih-Hsiang; Maher, Jaclyn P; Conroy, David E

    2015-01-01

    Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October-November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID:26844135

  11. The Central Analgesic Mechanism of YM-58483 in Attenuating Neuropathic Pain in Rats.

    PubMed

    Qi, Zeyou; Wang, Yaping; Zhou, Haocheng; Liang, Na; Yang, Lin; Liu, Lei; Zhang, Wei

    2016-10-01

    Calcium channel antagonists are commonly used to treat neuropathic pain. Their analgesic effects rely on inhibiting long-term potentiation, and neurotransmitters release in the spinal cord. Store-operated Ca(2+)channels (SOCCs) are highly Ca(2+)-selective cation channels broadly expressed in non-excitable cells and some excitable cells. Recent studies have shown that the potent inhibitor of SOCCs, YM-58483, has analgesic effects on neuropathic pain, but its mechanism is unclear. This experiment performed on spinal nerve ligation (SNL)-induced neuropathic pain model in rats tries to explore the mechanism, whereby YM-58483 attenuates neuropathic pain. The left L5 was ligated to produce the SNL neuropathic pain model in male Sprague-Dawley rats. The withdrawal threshold of rats was measured by the up-down method and Hargreaves' method before and after intrathecal administration of YM-58483 and vehicle. The SOCCs in the spinal dorsal horn were located by immunofluorescence. The expression of phosphorylated ERK and phosphorylated CREB, CD11b, and GFAP proteins in spinal level was tested by Western blot, while the release of proinflammatory cytokines (IL-1β, TNF-α, PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). Intrathecal YM-58483 at the concentration of 300 μM (1.5 nmol) and 1000 μM (10 nmol) produced a significant central analgesic effect on the SNL rats, compared with control + vehicle (n = 7, P < 0.001). However, both could not prevent the development of neuropathic pain, compared with normal + saline (P < 0.001). Immunofluorescent staining revealed that Orai1 and STIM1 (the two key components of SOCCs) were located in the spinal dorsal horn neurons. Western blot showed that YM-58483 could decrease the levels of P-ERK and P-CREB (n = 10, #P < 0.05), without affecting the expression of CD11b and GFAP (n = 10, #P > 0.05). YM-58483 also inhibited the release of spinal cord IL-1β, TNF-α, and PGE2, compared with control

  12. Evaluation of neck circumference as a predictor of central obesity and insulin resistance in Chinese adults

    PubMed Central

    Wang, Xuhong; Zhang, Ning; Yu, Caiguo; Ji, Zhili

    2015-01-01

    Objectives: To evaluate whether neck circumference (NC) could be used as a valid and effective method for identifying obesity and insulin resistance (IR) in Chinese adults. Methods: A total of 3307 adults aged 20-65 years were randomly recruited from two communities of Tongzhou, Beijing. Height, weight, waist circumference (WC), hip circumference (HC), neck circumference (NC), blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), total cholesterol (TC), serum triglyceride (TG), High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Urinary albumin (UAlb) were measured. Pearson correlation coefficient was used to explore the relationship between NC and other measurements. Furthermore, the best cutoff values of NC for central obesity identification were determined by applying the receiver operating characteristic (ROC) curve analysis. Results: NC correlated positively with BMI, SBP and WC In both sexes. Both WC and NC correlated significantly positively with IR. A positive correlation between NC and FPG as well as a negative correlation between NC and HDL were found in obese men. NC≥38.5 cm for men and ≥34.5 cm for women were determined to be the best cutoff levels for identifying subjects with central obesity, with 82.9% accuracy for men and 79.9% accuracy for women. Conclusions: NC correlated positively with BMI and WC in both genders, indicating that NC could be used as a valid marker for both overall obesity and central obesity. In addition, measuring NC was shown to be a useful test for IR identification. Large number of NC is suggested to be associated with high risk of developing metabolic disorders, such as diabetes and dyslipidemia. PMID:26770540

  13. Rats with altered behaviour following nerve injury show evidence of centrally altered thyroid regulation.

    PubMed

    Kilburn-Watt, E; Banati, R B; Keay, K A

    2014-08-01

    The co-morbidity of mood disturbance, in a proportion of patients, is now described across a wide range of chronic disease states. Similarly, a 'Low Thyroid Syndrome' is also reported in a proportion of individuals with chronic diseases. Here, we report on central changes in an animal model of inflammatory stress in which altered social behaviour, representing social disability, persists in a sub-group of rats following injury. We showed in an earlier study that rats with social disability following injury have significantly decreased peripheral thyroid hormones, with no increase in Thyroid Stimulating Hormone (TSH). Only rats identified by behavioural change showed changes in hypothalamic gene expression. In whole hypothalamus extracted RNA, relative expression of mRNA for Thyrotrophin-releasing hormone (TRH) was significantly down-regulated in disabled rats (p=0.039) and deiodinase 3 up-regulated (p=0.006) compared to controls. Specifically in the paraventricular nucleus (PVN), numbers of immunoreactive cells for deiodinase 3-like and thyroid hormone receptor beta-like proteins were decreased in the sub-group with disability compared to the control group (p=0.031 and p=0.011 respectively). In rats with behavioural change post-injury, down-regulation of TRH provides an explanation for the failure of the hypothalamo-pituitary-thyroid (HPT) axis to respond to the post-injury decrease in thyroxine. Decreased local expression of deiodinase 3 protein, resulting in a local increase in T3, offers an explanation for down regulation of TRH in the hypophysiotrophic TRH neurons. It is possible that, in a sub-group of animals identified behaviourally, a mechanism resulting in hypothalamic down-regulation of the HPT axis persists following inflammatory injury. PMID:25069097

  14. Tryptophan-induced central fatigue in exercising rats is related to serotonin content in preoptic area.

    PubMed

    Soares, Danusa Dias; Coimbra, Cândido Celso; Marubayashi, Umeko

    2007-03-30

    To assess the effects of increased hypothalamic tryptophan (TRP) availability on 5-HT content in preoptic area on thermoregulation and work production during exercise on treadmill, 20.3 microM of L-TRP (n=7) or 0.15M NaCl (n=6) was injected into the lateral cerebral ventricle of male Wistar rats immediately before the animals started running (18 m min(-1) 5% inclination). Exercise time to fatigue (min), and workload (kgm) were analysed. Core temperature was measured by telemetry. At fatigue, brains were quickly removed and preoptic area (POA), hypothalamus (HP), frontal cortex (FC), hippocampi (HC) were rapidly dissected and frozen immediately in dry ice. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured by HPLC. TRP-exercised rats showed the highest content of 5-HT in the POA and the lowest in the hippocampi compared to the rested and SAL-exercised rats. An inverse relationship between TF and a direct correlation with body temperature changes and POA-5HT levels were observed. A correlation between HC 5-HT content and TF was also found. However, there was no correlation between HC 5-HT content and changes in Tb at fatigue. Finally, our results bring further evidences that increased 5-HT content in POA is involved with an increase in heat production during exercise. In addition, the direct correlation of 5-HT level in hippocampi and TF of TRP-exercised rats suggests that this brain area is also related to motor activity control during exercise. In conclusion, our data indicated that tryptophan-induced central fatigue in exercising rats is related to serotonin content in preoptic area. PMID:17280786

  15. 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

  16. 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

  17. 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

  18. Intracerebroventricular delivery of self-complementary adeno-associated virus serotype 9 to the adult rat brain.

    PubMed

    Donsante, A; McEachin, Z; Riley, J; Leung, C H; Kanz, L; O'Connor, D M; Boulis, N M

    2016-05-01

    Gene therapy for the central nervous system is poised to become a powerful treatment for numerous neurological disorders. Adeno-associated viral vectors based on serotype 9 (AAV9) have proven themselves to be strong candidates for delivering gene-based therapies throughout the brain and spinal cord when administered intravenously, intrathecally, intracisternally, and intracerebroventricularly (i.c.v.). Previous studies of i.c.v.-delivered self-complimentary AAV9 have been performed in neonatal mice with delivery of a single dose. However, before clinical trials can be considered, more information is required about the dose-response relationship for transduction efficiency in adult animals. In the current study, three doses of self-complementary AAV9 were administered to adult rats. High levels of transduction were observed in the hippocampus, cerebellum and cerebral cortex, and transduction increased with increasing dosage. Both neurons and astrocytes were transduced. There was no evidence of astrocytosis at the doses tested. Preliminary results from pigs receiving i.c.v. self-complementary AAV9 are also presented. The results of this study will serve to inform dosing studies in large animal models before clinical testing. PMID:26824881

  19. The Angiotensin II Type 2 (AT2) Receptor Promotes Axonal Regeneration in the Optic Nerve of Adult Rats

    PubMed Central

    Lucius, Ralph; Gallinat, Stefan; Rosenstiel, Philip; Herdegen, Thomas; Sievers, Jobst; Unger, Thomas

    1998-01-01

    The renin-angiotensin system (RAS) has been traditionally linked to blood pressure and volume regulation mediated through the angiotensin II (ANG II) type 1 (AT1) receptor. Here we report that ANG II via its ANG II type 2 (AT2) receptor promotes the axonal elongation of postnatal rat retinal explants (postnatal day 11) and dorsal root ganglia neurons in vitro, and, moreover, axonal regeneration of retinal ganglion cells after optic nerve crush in vivo. In retinal explants, ANG II (10−7–10−5 M) induced neurite elongation via its AT2 receptor, since the effects were mimicked by the AT2 receptor agonist CGP 42112 (10−5 M) and were entirely abolished by costimulation with the AT2 receptor antagonist PD 123177 (10−5 M), but not by the AT1 receptor antagonist losartan (10−5 M). To investigate whether ANG II is able to promote axonal regeneration in vivo, we performed optic nerve crush experiments in the adult rats. After ANG II treatment (0.6 nmol), an increased number of growth-associated protein (GAP)-43–positive fibers was detected and the regenerating fibers regularly crossed the lesion site (1.6 mm). Cotreatment with the AT2 receptor antagonist PD 123177 (6 nmol), but not with the AT1 receptor antagonist losartan (6 nmol), completely abolished the ANG II–induced axonal regeneration, providing for the first time direct evidence for receptor-specific neurotrophic action of ANG II in the central nervous system of adult mammals and revealing a hitherto unknown function of the RAS. PMID:9705948

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Central cardiovascular actions of L-homocysteine microinjected into ventrolateral medullary autonomic areas of the rat.

    PubMed

    Takemoto, Yumi

    2016-09-01

    Elevated L-homocysteine concentrations in the plasma and cerebrospinal fluid are related to cardiovascular and neuronal diseases, and could contribute to disease development. However, the central cardiovascular actions of L-homocysteine in two important autonomic regulating areas remain unknown: the rostral ventrolateral medulla (RVLM), including pre-sympathetic neurons, and the caudal ventrolateral medulla (CVLM), including interneurons projecting to pre-sympathetic neurons in the RVLM. Therefore, the aim of the current study was to examine the influence of L-homocysteine microinjected into the RVLM and CVLM areas on changes in arterial blood pressure (ABP) and heart rate (HR) of anesthetized rats, as well as the influence of ionotropic excitatory amino acid (iEAA) receptors on the central actions of L-homocysteine. L-Homocysteine solutions were microinjected into the RVLM and CVLM, which were defined according to pressor and depressor responses to L-glutamate microinjections, respectively. ABP and HR increased in the RVLM and decreased in the CVLM after microinjection with L-homocysteine, similar to L-glutamate, in a dose-dependent manner, suggesting mediation of EAA receptors. Prior microinjection of the N-methyl-D-aspartate (NMDA) iEAA receptor antagonist MK801, but not the non-NMDA receptor antagonist CNQX, abolished the observed responses to L-homocysteine in both the RVLM and CVLM. These results indicate the central cardiovascular actions of L-homocysteine via MK801-sensitive receptors of the medullary autonomic neurons in the rat RVLM and CVLM. It remains unknown if the central cardiovascular actions are related to cardiovascular diseases after endogenously and locally augmented L-homocysteine production by disordered metabolism. Further studies on functional significance of L-homocysteine may provide some clue to understand its toxic mechanism. PMID:27178024

  9. 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

  10. Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals.

    PubMed

    Kumamoto, Eiichi; Fujita, Tsugumi

    2016-01-01

    Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a pivotal role in regulating nociceptive transmission. The TRP channels are activated by various plant-derived chemicals. Although stereoisomers activate or modulate ion channels in a distinct manner, this phenomenon is not fully addressed for TRP channels. By applying the whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices, we found out that all of plant-derived chemicals, carvacrol, thymol, carvone and cineole, increase the frequency of spontaneous excitatory postsynaptic current, a measure of the spontaneous release of l-glutamate from nerve terminals, by activating TRP channels. The presynaptic activities were different between stereoisomers (carvacrol and thymol; (-)-carvone and (+)-carvone; 1,8-cineole and 1,4-cineole) in the extent or the types of TRP channels activated, indicating that TRP channels in the SG are activated by stereoisomers in a distinct manner. This result could serve to know the properties of the central terminal TRP channels that are targets of drugs for alleviating pain. PMID:27483289