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Sample records for adult rat model

  1. Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.

    PubMed

    Morris, S A; Kelso, M L; Liput, D J; Marshall, S A; Nixon, K

    2010-02-01

    Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on

  2. Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome.

    PubMed

    Gil-Mohapel, Joana; Boehme, Fanny; Patten, Anna; Cox, Adrian; Kainer, Leah; Giles, Erica; Brocardo, Patricia S; Christie, Brian R

    2011-04-12

    Exposure to ethanol during pregnancy can be devastating to the developing nervous system, leading to significant central nervous system dysfunction. The hippocampus, one of the two brain regions where neurogenesis persists into adulthood, is particularly sensitive to the teratogenic effects of ethanol. In the present study, we tested a rat model of fetal alcohol syndrome (FAS) with ethanol administered via gavage throughout all three trimester equivalents. Subsequently, we assessed cell proliferation, as well as neuronal survival, and differentiation in the dentate gyrus of the hippocampus of adolescent (35 days old), young adult (60 days old) and adult (90 days old) Sprague-Dawley rats. Using both extrinsic (bromodeoxyuridine) and intrinsic (Ki-67) markers, we observed no significant alterations in cell proliferation and survival in ethanol-exposed animals when compared with their pair-fed and ad libitum controls. However, we detected a significant increase in the number of new immature neurons in animals that were exposed to ethanol throughout all three trimester equivalents. This result might reflect a compensatory mechanism to counteract the deleterious effects of prenatal ethanol exposure or an ethanol-induced arrest of the neurogenic process at the early neuronal maturation stages. Taken together these results indicate that exposure to ethanol during the period of brain development causes a long-lasting dysregulation of the neurogenic process, a mechanism that might contribute, at least in part, to the hippocampal deficits that have been reported in rodent models of FAS.

  3. Histological correlates of N40 auditory evoked potentials in adult rats after neonatal ventral hippocampal lesion: animal model of schizophrenia.

    PubMed

    Romero-Pimentel, A L; Vázquez-Roque, R A; Camacho-Abrego, I; Hoffman, K L; Linares, P; Flores, G; Manjarrez, E

    2014-11-01

    The neonatal ventral hippocampal lesion (NVHL) is an established neurodevelopmental rat model of schizophrenia. Rats with NVHL exhibit several behavioral, molecular and physiological abnormalities that are similar to those found in schizophrenics. Schizophrenia is a severe psychiatric illness characterized by profound disturbances of mental functions including neurophysiological deficits in brain information processing. These deficits can be assessed by auditory evoked potentials (AEPs), where schizophrenics exhibit abnormalities in amplitude, duration and latency of such AEPs. The aim of the present study was to compare the density of cells in the temporal cerebral cortex and the N40-AEP of adult NVHL rats versus adult sham rats. We found that rats with NVHL exhibit significant lower amplitude of the N40-AEP and a significant lower number of cells in bilateral regions of the temporal cerebral cortex compared to sham rats. Because the AEP recordings were obtained from anesthetized rats, we suggest that NVHL leads to inappropriate innervation in thalamic-cortical pathways in the adult rat, leading to altered function of cortical networks involved in processing of primary auditory information.

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

    PubMed

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

    2013-01-01

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

  5. Characterization of a Graded Cervical Hemicontusion Spinal Cord Injury Model in Adult Male Rats

    PubMed Central

    Dunham, Kelly A.; Siriphorn, Akkradate; Chompoopong, Supin

    2010-01-01

    Abstract Most experimental models of spinal cord injury (SCI) in rodents induce damage in the thoracic cord and subsequently examine hindlimb function as an indicator of recovery. In these models, functional recovery is most attributable to white-matter preservation and is less influenced by grey-matter sparing. In contrast, most clinical cases of SCI occur at the lower cervical levels, a region in which both grey-matter and white-matter sparing contribute to functional motor recovery. Thus experimental cervical SCI models are beginning to be developed and used to assess protective and pharmacological interventions following SCI. The objective of this study was to characterize a model of graded cervical hemicontusion SCI with regard to several histological and behavioral outcome measures, including novel forelimb behavioral tasks. Using a commercially available rodent spinal cord impactor, adult male rats received hemicontusion SCI at vertebral level C5 at 100, 200, or 300 kdyn force, to produce mild, moderate, or severe injury severities. Tests of skilled and unskilled forelimb and locomotor function were employed to assess functional recovery, and spinal cord tissue was collected to assess lesion severity. Deficits in skilled and unskilled forelimb function and locomotion relating to injury severity were observed, as well as decreases in neuronal numbers, white-matter area, and white-matter gliosis. Significant correlations were observed between behavioral and histological data. Taken together, these data suggest that the forelimb functional and locomotor assessments employed here are sensitive enough to measure functional changes, and that this hemicontusion model can be used to evaluate potential protective and regenerative therapeutic strategies. PMID:21087156

  6. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    PubMed Central

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

  7. [The role of prenatal hyperandrogenism on lipid metabolism during adult life in a rat model].

    PubMed

    Heber, María F; Vélez, Leandro M; Ferreira, Silvana R; Amalfi, Sabrina; Motta, Alicia B

    2012-01-01

    Polycystic ovary syndrome (PCOS) is one of the commonest endocrine diseases that affect women in their reproductive ages; however, the etiology of the syndrome remains unknown. A hypothesis proposes that during gestation increased exposure of androgen would induce fetal programming that may increase the risk of PCOS development during the adult life. By means of a prenatally hyperandrogenized (HA) rat model we demonstrated the importance of determining the lipid profile at early ages. HA induced two different phenotypes: ovulatory and anovulatory PCOS. HA did not modify total cholesterol but decreased HDL cholesterol and increased both LDL and tryglicerides (TG) when compared with controls. Both, the ratio total cholesterol: HDL (marker of cardiovascular risk) and TG:HDL (marker of metabolic syndrome) were increased in the HA group with respect to controls. In addition, these abnormalities were stronger in the anovulatory than ovulatory phenotype. Our results point out the need to find early markers of PCOS in girls or adolescents with increased risk to develop PCOS (as in daughters of women with PCOS).

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

    PubMed

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

    2016-04-01

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

  9. Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD.

    PubMed

    Somkuwar, S S; Kantak, K M; Bardo, M T; Dwoskin, L P

    2016-02-01

    Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5mg/kg) or water vehicle provided Monday-Friday from postnatal days 28-55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituted an adverse consequence associated with increased risk for cocaine abuse liability.

  10. Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

    PubMed Central

    Somkuwar, S.S.; Kantak, K.M.; Bardo, M.T.; Dwoskin, L.P.

    2016-01-01

    Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5 mg/kg) or water vehicle provided Monday-Friday from postnatal day 28–55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituting an adverse consequence associated with increased risk for cocaine abuse liability. PMID:26657171

  11. Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

    PubMed

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-02-14

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  12. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    PubMed Central

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-01-01

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life. PMID:28216584

  13. Use of an Adult Rat Retinal Explant Model for Screening of Potential Retinal Ganglion Cell Neuroprotective Therapies

    PubMed Central

    Bull, Natalie D.; Johnson, Thomas V.; Welsapar, Guncha; DeKorver, Nicholas W.; Tomarev, Stanislav I.

    2011-01-01

    Purpose. To validate an established adult organotypic retinal explant culture system for use as an efficient medium-throughput screening tool to investigate novel retinal ganglion cell (RGC) neuroprotective therapies. Methods. Optimal culture conditions for detecting RGC neuroprotection in rat retinal explants were identified. Retinal explants were treated with various recognized, or purported, neuroprotective agents and cultured for either 4 or 7 days ex vivo. The number of cells surviving in the RGC layer (RGCL) was quantified using histologic and immunohistochemical techniques, and statistical analyses were applied to detect neuroprotective effects. Results. The ability to replicate previously reported in vivo RGC neuroprotection in retinal explants was verified by demonstrating that caspase inhibition, brain-derived neurotrophic factor treatment, and stem cell transplantation all reduced RGCL cell loss in this model. Further screening of potential neuroprotective pharmacologic agents demonstrated that betaxolol, losartan, tafluprost, and simvastatin all alleviated RGCL cell loss in retinal explants, supporting previous reports. However, treatment with brimonidine did not protect RGCL neurons from death in retinal explant cultures. Explants cultured for 4 days ex vivo proved most sensitive for detecting neuroprotection. Conclusions. The current adult rat retinal explant culture model offers advantages over other models for screening potential neuroprotective drugs, including maintenance of neurons in situ, control of environmental conditions, and dissociation from other factors such as intraocular pressure. Verification that neuroprotection by previously identified RGC-protective therapies could be replicated in adult retinal explant cultures suggests that this model could be used for efficient medium-throughput screening of novel neuroprotective therapies for retinal neurodegenerative disease. PMID:21345987

  14. Development of multi-route physiologically-based pharmacokinetic models for ethanol in the adult, pregnant, and neonatal rat.

    PubMed

    Martin, Sheppard A; McLanahan, Eva D; El-Masri, Hisham; LeFew, William R; Bushnell, Philip J; Boyes, William K; Choi, Kyoungju; Clewell, Harvey J; Campbell, Jerry L

    2012-09-01

    Biofuel blends of 10% ethanol (EtOH) and gasoline are common in the USA, and higher EtOH concentrations are being considered (15-85%). Currently, no physiologically-based pharmacokinetic (PBPK) models are available to describe the kinetics of EtOH-based biofuels. PBPK models were developed to describe life-stage differences in the kinetics of EtOH alone in adult, pregnant, and neonatal rats for inhalation, oral, and intravenous routes of exposure, using data available in the open literature. Whereas ample data exist from gavage and intravenous routes of exposure, kinetic data from inhalation exposures are limited, particularly at concentrations producing blood and target tissue concentrations associated with developmental neurotoxicity. Compared to available data, the three models reported in this paper accurately predicted the kinetics of EtOH, including the absorption, peak concentration, and clearance across multiple datasets. In general, model predictions for adult and pregnant animals matched inhalation and intravenous datasets better than gavage data. The adult model was initially better able to predict the time-course of blood concentrations than was the neonatal model. However, after accounting for age-related changes in gastric uptake using the calibrated neonate model, simulations consistently reproduced the early kinetic behavior in blood. This work provides comprehensive multi-route life-stage models of EtOH pharmacokinetics and represents a first step in development of models for use with gasoline-EtOH blends, with additional potential applicability in investigation of the pharmacokinetics of EtOH abuse, addiction, and toxicity.

  15. Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder.

    PubMed

    Roth, Tania L; Zoladz, Phillip R; Sweatt, J David; Diamond, David M

    2011-07-01

    Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have been linked with memory, stress, and neuropsychiatric disorders. Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. Adult male Sprague-Dawley rats were given psychosocial stress composed of two acute cat exposures in conjunction with 31 days of daily social instability. These manipulations have been shown previously to produce physiological and behavioral sequelae in rats that are comparable to symptoms observed in traumatized people with PTSD. We then assessed Bdnf DNA methylation patterns (at exon IV) and gene expression. We have found here that the psychosocial stress regimen significantly increased Bdnf DNA methylation in the dorsal hippocampus, with the most robust hypermethylation detected in the dorsal CA1 subregion. Conversely, the psychosocial stress regimen significantly decreased methylation in the ventral hippocampus (CA3). No changes in Bdnf DNA methylation were detected in the medial prefrontal cortex or basolateral amygdala. In addition, there were decreased levels of Bdnf mRNA in both the dorsal and ventral CA1. These results provide evidence that traumatic stress occurring in adulthood can induce CNS gene methylation, and specifically, support the hypothesis that epigenetic marking of the Bdnf gene may underlie hippocampal dysfunction in response to traumatic stress. Furthermore, this work provides support for the speculative notion that altered hippocampal Bdnf DNA methylation is a cellular mechanism underlying the persistent cognitive deficits which are prominent features of the pathophysiology of PTSD.

  16. Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat

    PubMed Central

    Leroy, Claire; Pierre, Karin; Simpson, Ian A.; Pellerin, Luc; Vannucci, Susan J.; Nehlig, Astrid

    2013-01-01

    The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24 h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12 h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4 h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand. PMID:21624469

  17. Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats

    PubMed Central

    Sadek, Bassem; Saad, Ali; Latacz, Gniewomir; Kuder, Kamil; Olejarz, Agnieszka; Karcz, Tadeusz; Stark, Holger; Kieć-Kononowicz, Katarzyna

    2016-01-01

    A series of twelve novel non-imidazole-based ligands (3–14) was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R). The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3–14) tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES)-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally), whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ) model. Moreover, the protective effect observed for ligand 14 in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR) but not the brain-penetrant H2R antagonist zolantidine (ZOL), demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by 4 in PTZ model and the moderate protective effect by 14 in strychnine (STR) model. Moreover, the experimental and in silico estimation of properties such as metabolism was performed for five selected test compounds. Also, lipophilicity using planar reversed-phase thin-layer chromatography method was included for better understanding of the molecular properties of the tested compounds. Additionally, the absorption, distribution, metabolism, and elimination and toxicity parameters were evaluated for the most promising compounds 2, 4, 6, 7, and 14 utilizing in vitro methods. These interesting results highlight the potential of H3R ligands as new antiepileptic drugs or as adjuvants to available epilepsy medications. PMID:27932863

  18. Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats.

    PubMed

    Sadek, Bassem; Saad, Ali; Latacz, Gniewomir; Kuder, Kamil; Olejarz, Agnieszka; Karcz, Tadeusz; Stark, Holger; Kieć-Kononowicz, Katarzyna

    2016-01-01

    A series of twelve novel non-imidazole-based ligands (3-14) was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R). The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3-14) tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES)-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally), whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ) model. Moreover, the protective effect observed for ligand 14 in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR) but not the brain-penetrant H2R antagonist zolantidine (ZOL), demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by 4 in PTZ model and the moderate protective effect by 14 in strychnine (STR) model. Moreover, the experimental and in silico estimation of properties such as metabolism was performed for five selected test compounds. Also, lipophilicity using planar reversed-phase thin-layer chromatography method was included for better understanding of the molecular properties of the tested compounds. Additionally, the absorption, distribution, metabolism, and elimination and toxicity parameters were evaluated for the most promising compounds 2, 4, 6, 7, and 14 utilizing in vitro methods. These interesting results highlight the potential of H3R ligands as new antiepileptic drugs or as adjuvants to available epilepsy medications.

  19. Differential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?

    PubMed

    Karanges, Emily; Li, Kong M; Motbey, Craig; Callaghan, Paul D; Katsifis, Andrew; McGregor, Iain S

    2011-05-01

    Selective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11-12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19-20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms

  20. Pay attention to impulsivity: modelling low attentive and high impulsive subtypes of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female rats.

    PubMed

    Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Harte, Michael K; Barnes, Samuel A; Marshall, Kay M; Neill, Joanna C

    2014-08-01

    Varying levels of attention and impulsivity deficits are core features of the three subtypes of adult attention deficit-hyperactivity disorder (ADHD). To date, little is known about the neurobiological correlates of these subtypes. Development of a translational animal model is essential to improve our understanding and improve therapeutic strategies. The 5-choice continuous performance task (5C-CPT) in rats can be used to examine different forms of attention and impulsivity. Adult rats were trained to pre-set 5C-CPT criterion and subsequently separated into subgroups according to baseline levels of sustained attention, vigilance, premature responding and response disinhibition in the 5C-CPT. The behavioural subgroups were selected to represent the different subtypes of adult ADHD. Consequently, effects of the clinically used pharmacotherapies (methylphenidate and atomoxetine) were assessed in the different subgroups. Four subgroups were identified: low-attentive (LA), high-attentive (HA), high-impulsive (HI) and low-impulsive (LI). Methylphenidate and atomoxetine produced differential effects in the subgroups. Methylphenidate increased sustained attention and vigilance in LA animals, and reduced premature responding in HI animals. Atomoxetine also improved sustained attention and vigilance in LA animals, and reduced response disinhibition and premature responding in HI animals. This is the first study using adult rats to demonstrate the translational value of the 5C-CPT to select subgroups of rats, which may be used to model the subtypes observed in adult ADHD. Our findings suggest that this as an important paradigm to increase our understanding of the neurobiological underpinnings of adult ADHD-subtypes and their response to pharmacotherapy.

  1. Chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in adult spontaneously hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD).

    PubMed

    Pires, Vanessa A; Pamplona, Fabrício A; Pandolfo, Pablo; Prediger, Rui D S; Takahashi, Reinaldo N

    2010-12-20

    The spontaneously hypertensive rat (SHR) is frequently used as an experimental model for the study of attention deficit hyperactivity disorder (ADHD) since it displays behavioural and neurochemical features of ADHD. Increasing evidence suggests that caffeine might represent an important therapeutic tool for the treatment of ADHD and we recently demonstrated that the acute administration of caffeine improves several learning and memory impairments in adult SHR rats. Here we further evaluated the potential of caffeine in ADHD therapy. Female Wistar (WIS) and SHR rats were treated with caffeine (3mg/kg, i.p.) or methylphenidate (MPD, 2mg/kg, i.p.) for 14 consecutive days during the prepubertal period (post-natal days 25-38) and they were tested later in adulthood in the object-recognition task. WIS rats discriminated all the objects used, whereas SHR were not able to discriminate pairs of objects with subtle structural differences. Chronic treatment with caffeine or MPD improved the object-recognition deficits in SHR rats. Surprisingly, these treatments impaired the short-term object-recognition ability in adult WIS rats. The present drug effects are independent of changes in locomotor activity, arterial blood pressure and body weight in both rat strains. These findings suggest that chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in discriminative learning impairments of SHR, suggesting caffeine as an alternative therapeutic strategy for the early management of ADHD symptoms. Nevertheless, our results also emphasize the importance of a correct diagnosis and the caution in the use of stimulant drugs such as caffeine and MPD during neurodevelopment since they can disrupt discriminative learning in non-ADHD phenotypes.

  2. Development of PBPK Models for Gasoline in Adult and Pregnant Rats and their Fetuses

    EPA Science Inventory

    Concern for potential developmental effects of exposure to gasoline-ethanol blends has grown along with their increased use in the US fuel supply. Physiologically-based pharmacokinetic (PBPK) models for these complex mixtures were developed to address dosimetric issues related to...

  3. 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

  4. Spike-Wave Discharges in Adult Sprague-Dawley Rats and Their Implications for Animal Models of Temporal Lobe Epilepsy

    PubMed Central

    Pearce, Patrice S.; Friedman, Daniel; LaFrancois, John J.; Iyengar, Sloka S.; Fenton, André A.; MacLusky, Neil J.; Scharfman, Helen E

    2014-01-01

    Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. GAERS and Wag/Rij rat strains exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies about the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2–3 month old naïve female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest and they continued for months. Males exhibited SWDs only after 3 months of age, consistent with previous reports [1]. Housing in atypical lighting during early life appeared to facilitate the incidence SWDs. SWDs were often accompanied by behaviors similar to stage 1–2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to theta rhythm during exploration for a given animal, typically 7–8 Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250 Hz) during SWDs, suggesting neuronal activity in hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal and cortical neurons in does not prevent SWDs, at least in this animal model. The results

  5. Scheduled access alcohol drinking by alcohol-preferring (P) and high-alcohol-drinking (HAD) rats: modeling adolescent and adult binge-like drinking.

    PubMed

    Bell, Richard L; Rodd, Zachary A; Engleman, Eric A; Toalston, Jamie E; McBride, William J

    2014-05-01

    Binge alcohol drinking continues to be a public health concern among today's youth and young adults. Moreover, an early onset of alcohol use, which usually takes the form of binge drinking, is associated with a greater risk for developing alcohol use disorders. Given this, it is important to examine this behavior in rat models of alcohol abuse and dependence. Toward that end, the objective of this article is to review findings on binge-like drinking by selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of rats. As reviewed elsewhere in this special issue, the P line meets all, and the HAD line meets most, of the proposed criteria for an animal model of alcoholism. One model of binge drinking is scheduled ethanol access during the dark cycle, which has been used by our laboratory for over 20 years. Our laboratory has also adopted a protocol involving the concurrent presentation of multiple ethanol concentrations. When this protocol is combined with limited access, ethanol intake is maximized yielding blood ethanol levels (BELs) in excess, sometimes greatly in excess, of 80 mg%. By extending these procedures to include multiple scheduled ethanol access sessions during the dark cycle for 5 consecutive days/week, P and HAD rats consume in 3 or 4 h as much as, if not more than, the amount usually consumed in a 24 h period. Under certain conditions, using the multiple scheduled access procedure, BELs exceeding 200 mg% can be achieved on a daily basis. An overview of findings from studies with other selectively bred, inbred, and outbred rats places these findings in the context of the existing literature. Overall, the findings support the use of P and HAD rats as animal models to study binge-like alcohol drinking and reveal that scheduled access procedures will significantly increase ethanol intake by other rat lines and strains as well.

  6. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN ADULT AND DEVELOPING SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

  7. Gene expression profiling of the hippocampal dentate gyrus in an adult toxicity study captures a variety of neurodevelopmental dysfunctions in rat models of hypothyroidism.

    PubMed

    Shiraki, Ayako; Saito, Fumiyo; Akane, Hirotoshi; Akahori, Yumi; Imatanaka, Nobuya; Itahashi, Megu; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    We previously found that developmental hypothyroidism changed the expression of genes in the rat hippocampal dentate gyrus, a brain region where adult neurogenesis is known to occur. In the present study, we performed brain region-specific global gene expression profiling in an adult rat hypothyroidism model to see if it reflected the developmental neurotoxicity we saw in the developmental hypothyroidism model. Starting when male rats were 5 weeks old, we administered 6-propyl-2-thiouracil at a doses of 0, 0.1 and 10 mg kg(-1) body weight by gavage for 28 days. We selected four brain regions to represent both cerebral and cerebellar tissues: hippocampal dentate gyrus, cerebral cortex, corpus callosum and cerebellar vermis. We observed significant alterations in the expression of genes related to neural development (Eph family genes and Robo3) in the cerebral cortex and hippocampal dentate gyrus and in the expression of genes related to myelination (Plp1 and Mbp) in the hippocampal dentate gyrus. We observed only minor changes in the expression of these genes in the corpus callosum and cerebellar vermis. We used real-time reverse-transcription polymerase chain reaction to confirm Chrdl1, Hes5, Mbp, Plp1, Slit1, Robo3 and the Eph family transcript expression changes. The most significant changes in gene expression were found in the dentate gyrus. Considering that the gene expression profile of the adult dentate gyrus closely related to neurogenesis, 28-day toxicity studies looking at gene expression changes in adult hippocampal dentate gyrus may also detect possible developmental neurotoxic effects.

  8. Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression?

    PubMed

    Hansen, H H; Sánchez, C; Meier, E

    1997-12-01

    Chronic administration of the tricyclic antidepressant clomipramine to neonatal rats from postnatal days 8 to 21 is reported to induce several behavioral changes in adult life, and it may serve as an animal model of human depressive disorder. Findings include increased immobility time in the forced swim test and locomotor hyperactivity in the open field test. Clomipramine is a serotonergic reuptake inhibitor, which suggests that altered development of the serotonergic system could account for the observed behavioral changes in the adult rat. The present study was carried out with a selective serotonin reuptake inhibitor (SSRI) to investigate whether the serotonin system, in particular, is involved in the neonatal animal model. The substance, Lu 10-134-C (LU), was characterized in monoamine reuptake and receptor binding assays and found to be an SSRI. Rats received LU during postnatal days 8 to 21 (2.5-15 mg/kg b. i.d.), and they were assessed in open field, forced swim and social interaction tests at the age of 4 months. Behavior of LU-treated rats and saline controls did not differ in the open field and social interaction tests. However, in the forced swim tests LU-treated neonates showed prolonged immobility time compared with saline controls. In conclusion, chronic LU treatment during neonatal life produces long-term changes in the forced swim test, but not in the open field and social interaction tests. The behavioral changes in the forced swim test suggest that the central serotonergic system may be involved in the putative neonatal animal model of depression.

  9. Evaluation of bone formation guided by DNA/protamine complex with FGF-2 in an adult rat calvarial defect model.

    PubMed

    Shinozaki, Yosuke; Toda, Masako; Ohno, Jun; Kawaguchi, Minoru; Kido, Hirofumi; Fukushima, Tadao

    2014-11-01

    DNA/protamine complex paste (D/P) and D/P complex paste with Fibroblast Growth Factor-2 (FGF-2) (D/P-FGF) were prepared to investigate their new bone formation abilities using an ∼40-week-old rat calvarial defect model. It was found that D/P could release FGF-2 proportionally in an in vitro experiment with an enzyme-linked immunosorbent assay. It was also found that aging adversely affected self-bone healing of rats by comparison with the results in a previous study using 10-week-old rats. Microcomputed tomography and histopathological examinations showed that new bone formation abilities of D/P and D/P-FGF were superior to that of the control (sham operation). Control, D/P and D/P-FGF showed newly formed bone areas of 6.7, 58.3, and 67.0%, respectively, 3 months after the operation. Moreover, it was found that FGF-2 could support the osteoanagenesis ability of D/P. It was considered that FGF-2 could play an important role in new bone formation at early stages because it induced the genes such as collagen I, CBFA, OSX, and OPN, which are initiated first in the process of osteogenesis. Therefore, D/P-FGF will be a useful injectable biomaterial with biodegradable properties for the repair of bone defects in the elderly.

  10. MODELING VOLATILE ORGANIC COMPOUND PHARMACOKINETICS IN RAT PUPS

    EPA Science Inventory

    PBPK model predictions of internal dosimetry in young rats were compared to adult animals for benzene, chloroform (CHL), methylene chloride, methyl ethly ketone (MEK), perchloroethylene, and trichloroethylene.

  11. The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

    NASA Technical Reports Server (NTRS)

    Schultheis, Lester W.

    1999-01-01

    We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force

  12. Morphometric analysis of cortical bone upon the exposure to sustained delivery of anabolic promoting agents using adult male rats as a model.

    PubMed

    Tramontana, J; Benghuzzi, H; Tucci, M; Tsao, A; Hughes, J

    2001-01-01

    Several investigations have documented that the use of anabolic agents could promote osteogenesis and enhance bone ingrowth in traumatized bone. Previously, anabolic steroids have been shown to increase the mineralization of bone. However, their clinical use has been limited because of the unwanted virilizing activity. The previous studies used systemic administration of anabolic steroids, which subjects other tissues within the body to high concentrations of hormones. In addition, different anabolic/androgenic steroids have varying affinities to different cell types within tissues. The specific objectives of this study were (i) to histopathologically evaluate the structural changes associated with sustained delivery of testosterone (T), dihydrotestosterone (DHT), and androstendione (AED) using adult male rats as a model, and (ii) to morphometrically evaluate the cortical areas and length upon the exposure of the aforementioned hormones for 90 days. A total of 23 adult rats were randomly divided into five groups (group I = control, group II = sham, group III = AED, Group IV = T and group V = DHT treated). At the end of the treatments the animals were euthanized and the x-rays, blood, and bones were analyzed using standard laboratory protocols. Data obtained from this investigation revealed the following: (A) all treated femurs appeared healthy with no traumatic responses observed in comparison to control animals, (B) measurements of the inner perimeter of the bone on the endosteal side showed significant reduction in the androgen treated animals. This suggesting that the androgens caused increases in the cortical bone. The differences seen in the amount of reduction was in the following ease: T > DHT > AED. C) quantitative measurements of the cortical length showed slight increases in the cortical lengths in the androgen treated rats in comparison to the control.

  13. Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure

    PubMed Central

    Kantak, Kathleen M.; Barlow, Nicole; Tassin, David H.; Brisotti, Madeline F.; Jordan, Chloe J

    2014-01-01

    Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders). PMID:24800898

  14. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    PubMed

    Cunha, Fábio da Silva; Dalle Molle, Roberta; Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

  15. 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

  16. I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

    PubMed

    Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

    2005-01-01

    I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

  17. Effects of environmental tobacco smoke on adult rat brain biochemistry.

    PubMed

    Fuller, Brian F; Gold, Mark S; Wang, Kevin K W; Ottens, Andrew K

    2010-05-01

    Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of alphaII-spectrin by caspase-3 and the dephosphorylation of serine(116) on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, beta-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

  18. Hydrocephalus induced via intraventricular kaolin injection in adult rats.

    PubMed

    Shaolin, Z; Zhanxiang, W; Hao, X; Feifei, Z; Caiquan, H; Donghan, C; Jianfeng, B; Feng, L; Shanghang, S

    2015-01-01

    Hydrocephalus is a common neurological disease in humans, but a uniform and particularly effective hydrocephalic animal model amenable to proper appraisal and deep study has not yet been established. In this study, we attempted to construct a high-efficiency model of hydrocephalus via intraventricular kaolin injection. Adult male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 15) and the experimental group (n = 30). Kaolin was injected into the lateral ventricle of experimental animals. Control rats underwent the same procedure but received sterile saline injection instead of kaolin. All animals with kaolin injection into the lateral ventricle developed hydrocephalus according to magnetic resonance imaging (MRI) results (success rate up to 100%). Also, the Morris water maze (MWM) test demonstrated disturbed spatial learning and memory. Furthermore, there were significant differences between groups with respect to the histological changes in the periventricular tissue. Our results indicate that experimental hydrocephalus induced by lateral ventricle injection of kaolin in adult rats is feasible and may be widely used.

  19. Rat Endovascular Perforation Model

    PubMed Central

    Sehba, Fatima A.

    2014-01-01

    Experimental animal models of aneurysmal subarachnoid hemorrhage (SAH) have provided a wealth of information on the mechanisms of brain injury. The Rat endovascular perforation model (EVP) replicates the early pathophysiology of SAH and hence is frequently used to study early brain injury following SAH. This paper presents a brief review of historical development of the EVP model, details the technique used to create SAH and considerations necessary to overcome technical challenges. PMID:25213427

  20. Prenatal ethanol exposure increases brain cholesterol content in adult rats.

    PubMed

    Barceló-Coblijn, Gwendolyn; Wold, Loren E; Ren, Jun; Murphy, Eric J

    2013-11-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content are known to occur in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43 %, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total polyunsaturated fatty acids (PUFA), in the n-3/n-6 ratio, and in the 22:6n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of postnatal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats.

  1. Induction of c-fos mRNA expression in an in vitro hippocampal slice model of adult rats after kainate but not gamma-aminobutyric acid or bicuculline treatment.

    PubMed

    Massamiri, T; Khrestchatisky, M; Ben-Ari, Y

    1994-01-17

    Levels of gene expression following in vitro treatment of rat hippocampal slices with kainate, gamma-aminobutyric acid (GABA), or bicuculline were measured by the reverse transcription-coupled polymerase chain reaction method. Following a short-term exposure to kainate, c-fos gene expression was induced by 12-fold in the adult, but not the newborn, hippocampus. Under the same experimental conditions, zifl268 and brain-derived neurotrophic factor (BDNF) gene expression were unchanged. Our results also demonstrate a lack of induction of c-fos, zifl268 and BDNF after short-time treatment of either adult or newborn hippocampal slices with GABA or bicuculline. The relevance of the differential induction of gene expression in the adult and newborn in an in vitro hippocampal slice model as compared to previously described in vivo models is discussed.

  2. A MATHEMATICAL MODEL FOR THE ANDROGENIC REGULATION OF THE PROSTATE IN INTACT AND CASTRATE ADULT MALE RATS

    EPA Science Inventory

    An abstract that provides understanding for a mathematical model by Barton and Anderson, for the dynamics of androgenic synthesis, transport, metabolism, and regulation of the rodent ventral prostate.

  3. Enduring and sex-specific effects of adolescent social isolation in rats on adult stress reactivity.

    PubMed

    Weintraub, Ari; Singaravelu, Janani; Bhatnagar, Seema

    2010-07-09

    In adolescence, gender differences in rates of affective disorders emerge. For both adolescent boys and girls, peer relationships are the primary source of life stressors though adolescent girls are more sensitive to such stressors. Social stressors are also powerful stressors for non-human social species like rodents. In a rat model, we examined how social isolation during adolescence impacts stress reactivity and specific neural substrates in adult male and female rats. Rats were isolated during adolescence by single housing from day 30 to 50 of age and control rats were group housed. On day 50, isolated rats and control rats were re-housed in same-treatment same-sex groups. Adult female rats isolated as adolescents exhibited increased adrenal responses to acute and to repeated stress and exhibited increased hypothalamic vasopressin mRNA and BDNF mRNA in the CA3 hippocampal subfield. In contrast, adult male rats isolated as adolescents exhibited a lower corticosterone response to acute stress, exhibited a reduced state of anxiety as assessed in the elevated plus maze and reduced Orexin mRNA compared to adult males group-housed as adolescents. These data point to a markedly different impact of isolation experienced in adolescence on endocrine and behavioral endpoints in males compared to females and identify specific neural substrates that may mediate the long-lasting effects of stress in adolescence.

  4. Development of Multi-Route Physiologically-based Pharmacokinetic Models for Ethanol in the Adult, Pregnant, and Neonatal Rat

    EPA Science Inventory

    Biofuel blends of 10% ethanol (EtOH) and gasoline are common in the United States, and higher EtOH concentrations are being considered (15-85%). Currently, no physiologically-based pharmacokinetic (PBPK) models are available to describe the kinetics of EtOH-based biofuels. PBPK...

  5. Curriculum Models in Adult Education.

    ERIC Educational Resources Information Center

    Langenbach, Michael

    This book describes several curriculum models currently used in the field of adult education in an effort to assist adult educators who develop curricula as a routine part of their jobs. The book is divided into 14 chapters that are grouped into 7 sections. Each section covers a type of educational program, and each chapter describes a specific…

  6. Predictive Modeling in Adult Education

    ERIC Educational Resources Information Center

    Lindner, Charles L.

    2011-01-01

    The current economic crisis, a growing workforce, the increasing lifespan of workers, and demanding, complex jobs have made organizations highly selective in employee recruitment and retention. It is therefore important, to the adult educator, to develop models of learning that better prepare adult learners for the workplace. The purpose of…

  7. Assessment Models for Adult Education.

    ERIC Educational Resources Information Center

    Snow, Ellen; And Others

    This handbook was developed to provide adult educators in Texas with sufficient background in assessment models to ensure confidence in recognizing and/or selecting appropriate measurement techniques and in using evaluation results to individualize and improve instruction for adult students. The handbook is based on information derived from a…

  8. Homocysteine Induces Glial Reactivity in Adult Rat Astrocyte Cultures.

    PubMed

    Longoni, Aline; Bellaver, Bruna; Bobermin, Larissa Daniele; Santos, Camila Leite; Nonose, Yasmine; Kolling, Janaina; Dos Santos, Tiago M; de Assis, Adriano M; Quincozes-Santos, André; Wyse, Angela T S

    2017-03-02

    Astrocytes are dynamic glial cells associated to neurotransmitter systems, metabolic functions, antioxidant defense, and inflammatory response, maintaining the brain homeostasis. Elevated concentrations of homocysteine (Hcy) are involved in the pathogenesis of age-related neurodegenerative disorders, such as Parkinson and Alzheimer diseases. In line with this, our hypothesis was that Hcy could promote glial reactivity in a model of cortical primary astrocyte cultures from adult Wistar rats. Thus, cortical astrocytes were incubated with different concentrations of Hcy (10, 30, and 100 μM) during 24 h. After the treatment, we analyzed cell viability, morphological parameters, antioxidant defenses, and inflammatory response. Hcy did not induce any alteration in cell viability; however, it was able to induce cytoskeleton rearrangement. The treatment with Hcy also promoted a significant decrease in the activities of Na(+), K(+) ATPase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as in the glutathione (GSH) content. Additionally, Hcy induced an increase in the pro-inflammatory cytokine release. In an attempt to elucidate the putative mechanisms involved in the Hcy-induced glial reactivity, we measured the nuclear factor kappa B (NFκB) transcriptional activity and heme oxygenase 1 (HO-1) expression, which were activated and inhibited by Hcy, respectively. In summary, our findings provide important evidences that Hcy modulates critical astrocyte parameters from adult rats, which might be associated to the aging process.

  9. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    PubMed

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  10. Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

    PubMed Central

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  11. Computational models of adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Cecchi, Guillermo A.; Magnasco, Marcelo O.

    2005-10-01

    Experimental results in recent years have shown that adult neurogenesis is a significant phenomenon in the mammalian brain. Little is known, however, about the functional role played by the generation and destruction of neurons in the context of an adult brain. Here, we propose two models where new projection neurons are incorporated. We show that in both models, using incorporation and removal of neurons as a computational tool, it is possible to achieve a higher computational efficiency that in purely static, synapse-learning-driven networks. We also discuss the implication for understanding the role of adult neurogenesis in specific brain areas like the olfactory bulb and the dentate gyrus.

  12. Gravitational Biology: The Rat Model

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  13. Distraction of skeletal muscle: evolution of a rat model.

    PubMed

    Green, Stuart A; Horton, Eric; Baker, Michael; Utkan, Ali; Caiozzo, Vincent

    2002-10-01

    To better study the effects of limb lengthening on skeletal muscle, the authors developed a rat model that uses a miniature external skeletal fixator applied to the tibia of an adult Sprague-Dawley rat. The mounting and lengthening protocols follow the principles developed by Ilizarov. With the initial version of the fixator, the rats had progressive equinus contractures develop because the calf muscles resisted elongation. By incorporating a footplate in the distraction apparatus, tibial lengthening can be achieved without concomitant equinus.

  14. Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model.

    PubMed

    Acosta, Sandra A; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David M; Diamond, David; Sanberg, Paul R; Bickford, Paula C; Kaneko, Yuji; Borlongan, Cesar V

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes.

  15. 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.

  16. 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

  17. Hypertension after bilateral kidney irradiation in young and adult rats

    SciTech Connect

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-09-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.

  18. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    DTIC Science & Technology

    1991-12-01

    during aggression in rats and some other myomorph species (e.g., Acomys cahirinus, Apcdemus sylvati- cus). Other species (e.g., MusM muau_...which occur when the young are handled. The author reports that, unlike rats, other rodent species (e.g., lab mice, Acomys cahirinus, Clethrionomys gajj... Acomys was removed from the mother’s cage, and during exploratory behavior in Apodemus gyiL vaticus. i1 Sewell, G.D. Ultrasonic signals from rodents

  19. Potassium currents in adult rat intracardiac neurones.

    PubMed Central

    Xi-Moy, S X; Dun, N J

    1995-01-01

    1. Properties of K+ currents were studied in isolated adult rat parasympathetic intracardiac neurones with the use of single-electrode voltage-clamp techniques. 2. A hyperpolarization-activated inward rectifier current was revealed when the membrane was clamped close to the resting level (-60 mV). The slowly developing inward relaxation had a mean amplitude of 450 pA at -150 mV, an activation threshold of -60 to -70 mV and a relaxation time constant of 41 ms at -120 mV. The current was reversibly blocked by Cs+ (1 mM) and became smaller with reduced [K+]o and [Na+]o, indicating that this inward rectifier current probably is a time- and voltage-dependent Na(+)-K+ current. 3. Step depolarizations from the holding potential of -80 mV evoked a transient (< 100 ms at -40 mV) outward K+ current (IA) which was blocked by 4-aminopyridine (4-AP, 1 mM). The time constants for IA inactivation were 20 ms at -50 mV and 16 ms at -20 mV. The steady-state activation and (removal of) inactivation curve showed a small overlap between -70 and -40 mV; the reversal potential of IA was close to EK. 4. Step hyperpolarizations from the depolarized potentials, i.e. -30 mV, revealed a slow inward relaxation associated with the deactivation of a time- and voltage-dependent current. The inward relaxation became faster at more hyperpolarized potentials and reversed at -85 and -53 mV in 4.7 and 15 mM [K+]o. This current was blocked by muscarine (20 microM) and Ba2+ (1 mM) but not affected by Cs+ (1 mM); this current may correspond to the M-current (IM). 5. Depolarization-activated outward K+ currents were evoked by holding the membrane close to the resting potential in the presence of tetrodotoxin (TTX, 3 microM), 4-AP (1 mM) and Ba2+ (1 mM). The amplitude of the outward relaxation and the tail current became smaller as the [K+]o was elevated. The outward tail current was reduced in a Ca(2+)-free solution and the residual current was eliminated by the addition of tetraethylammonium (TEA, 10 m

  20. Intermittent access to beer promotes binge-like drinking in adolescent but not adult Wistar rats.

    PubMed

    Hargreaves, Garth A; Monds, Lauren; Gunasekaran, Nathan; Dawson, Bronwyn; McGregor, Iain S

    2009-06-01

    Teenagers are more likely than adults to engage in binge drinking and could be more vulnerable to long-term brain changes following alcohol abuse. We investigated the possibility of excessive adolescent drinking in a rodent model in which beer (4.44% ethanol vol/vol) is presented to adult and adolescent male Wistar rats. Experiment 1 tracked ad libitum beer and water consumption in group-housed rats from postnatal day (PND) 28-96. Rats consumed an average of 7.8 g/kg/day of ethanol during adolescence (PND 34-55) and this gradually declined to a lower level of intake in adulthood (PND 56-93) of 3.9 g/kg/day. In Experiment 2, beer was made available to both adolescent (PND 29+) and adult (PND 57+) rats for 2h each day in a custom-built "lickometer" apparatus over 75 days. Access to beer was provided either 1 day out of every 3 ("intermittent" groups) or every day ("daily" groups). Relative to body weight, adolescent rats consumed more beer than adult rats in these limited access sessions. Adolescents with intermittent access consumed more than adolescents with daily access, a "binge"-like effect that was not observed in adult groups and that disappeared in adulthood. After 3 months of daily or intermittent alcohol consumption, the preference for beer versus sucrose was assessed. Rats previously kept under an intermittent schedule displayed a higher preference for beer relative to 3% sucrose, but only when testing occurred after 2 days of abstinence. In Experiment 3, adolescent (PND 30-37) and adult (PND 58-65) rats were given 20-min access to beer and their blood alcohol concentrations (BACs) were assessed. Adolescent groups consumed more alcohol than adults and showed higher BACS that were typical of human "binge" drinking (>80 mg/dL). Despite this, the correlation between BAC and beer intake was similar in both age groups. Together these results show that the intermittent presentation of alcohol itself appears to have subtle long-lasting effects on the motivation

  1. Adrenal and gonadal function in hypothyroid adult male rats.

    PubMed

    Tohei, A; Akai, M; Tomabechi, T; Mamada, M; Taya, K

    1997-01-01

    The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouraciltreated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH.

  2. Neonatal sensory deprivation promotes development of absence seizures in adult rats with genetic predisposition to epilepsy.

    PubMed

    Sitnikova, Evgenia

    2011-03-04

    Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence seizures appear after puberty and they are increased with age. It is known that (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the critical period of development, could enhance excitatory activity in the somatosensory cortex. It is hypothesized that the cortex may become more excitable after neonatal vibrissae removal, and this may precipitate absence seizures in adult rats. We found that whisker trimming during the first postnatal weeks caused more rapid development of EEG seizure activity in adult WAG/Rij rats. Epileptic discharges in the trimmed rats were more numerous (vs control), showed longer duration and often appeared in desynchronized and drowsy EEG. The number of absence-like spindle-shaped EEG events (spike-wave spindles) in the whisker-trimmed rats was higher than in control, especially during the intermediate sleep state. An age-dependent increase of intermediate sleep state was found in the trimmed rats, but not in the intact animals. We discuss epigenetic factors that can modulate absence epilepsy in genetically prone subjects.

  3. Chronic nicotine differentially alters cocaine-induced locomotor activity in adolescent vs. adult male and female rats.

    PubMed

    Collins, Stephanie L; Izenwasser, Sari

    2004-03-01

    Tobacco use is prevalent in the adolescent population. It is a major concern because tobacco is highly addictive and has also been linked to illicit drug use. There is not much research, however, on the interaction between nicotine and other stimulant drugs in animal models of early adolescence. This study examined the effects of chronic nicotine alone and on cocaine-stimulated activity in male and female periadolescent rats compared to male and female adult rats. During the seven-day nicotine pretreatment period, nicotine increased locomotor activity in all groups compared to vehicle controls. Male and female adult rats and female periadolescent rats developed sensitization to the locomotor-activating effects of nicotine over the 7-day treatment period, while male periadolescent rats did not. All groups treated with nicotine, however, exhibited sensitization to nicotine-induced repetitive motion over the 7-day nicotine treatment period. On day 8, male periadolescent rats pretreated with nicotine were more markedly sensitized to the locomotor-activating effects of cocaine than male adult rats, while female rats pretreated with nicotine were not sensitized to cocaine. In contrast, male and female periadolescent rats, but not adult rats, had increased amounts of repetitive beam breaks induced by cocaine after nicotine pretreatment. Overall, it appears that cross-sensitization to cocaine is greater in periadolescent than in adult rats, and that males are more sensitized than females. Thus, it may be that nicotine use during adolescence carries a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of cocaine abuse after nicotine use. This information should be taken into account so as to help us better understand the development of drug addiction in adolescents compared to adults.

  4. Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

    PubMed

    Nowak, Przemyslaw; Jochem, Jerzy; Zwirska-Korczala, Krystyna; Josko, Jadwiga; Noras, Lukasz; Kostrzewa, Richard M; Brus, Ryszard

    2008-04-01

    To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity several-fold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum--reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

  5. [In vitro organotypic cultivation of adult newt and rat retinas].

    PubMed

    Novikova, Iu P; Aleĭnikova, K S; Krasnov, M S; Poplinskaia, V A; Grigorian, E N

    2010-01-01

    Adult rat and newt retinas were studied during long organotypic 3D cultivation. A high proliferation level was discovered in the region of growth by applying DNA synthesis markers and in vitro mitosis registration in newt retina. Aggregates were formed in the retina spheroid cavity because dedifferentiated cells migrated into this region. Small cell populations in nuclear layers also had dividing and migration capacity. Rosette formation has been shown in newt retina. It is a characteristic of fetal retinal development under pathological conditions. The antiG FAP antibody dye demonstrated an increase in the parent M@uller cell population and generation of a small cell pool with short GFAP-extensions de novo. Recoverin expression studies detected its translocation from photoreceptor extensions to the cell bodies. Moreover, protein was presented in some cells inside the spheroid. It has been shown for the first time that cell proliferation occurred in the developing adult rat retinal spheroid in vitro; BrdU-positive cells and multiple mitoses were revealed in this zone. However, the source of proliferation was not in the peripheral retina, and stable macrophages and glial cells located among neurons of the inner nuclear layer had the ability to divide. The antiGFAP antibody showed an increase in GFAP fibers in the rat retina as well as in the newt retina. Recoverin translocated into photoreceptor perikaryons and the outer plexiform layer in cultivated rat retina. Interestingly, some cells with probably de novo expression of recoverin were discovered in rat and newt retinas.

  6. 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.

  7. Rapid neurobehavioral analysis of Pfiesteria piscicida effects in juvenile and adult rats.

    PubMed

    Levin, E D; Rezvani, A H; Christopher, N C; Glasgow, H B; Deamer-Melia, N J; Burkholder, J M; Moser, V C; Jensen, K

    2000-01-01

    The estuarine dinoflagellate Pfiesteria piscicida is known to kill fish and has been associated with neurocognitive deficits in humans. We have developed a rat model to demonstrate that exposure to Pfiesteria causes significant learning impairments. This has been repeatedly seen as a choice accuracy impairment during radial-arm maze learning. Pfiesteria-induced effects were also seen in a locomotor activity test in the figure-8 apparatus. The current studies used the short-term radial-arm maze acquisition, the figure-8 activity test, and the functional observational battery (FOB) to assess Pfiesteria-induced neurobehavioral effects in adult and juvenile rats. In study 1, the neurobehavioral potency of three different Pfiesteria cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed. Ninety-six (12 per group) adult female Sprague-Dawley rats were injected subcutaneously with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600 or 106,800 Pfiesteria cells per kilogram of rat body weight). One control group (N = 12) was injected with saline and one (N = 12) with aquarium water not containing Pfiesteria. All three of the Pfiesteria samples (p < 0.05) impaired choice accuracy over the first six sessions of training. At the time of the radial-arm maze choice accuracy impairment, no overt Pfiesteria-related effects were seen using an FOB, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the figure-8 apparatus, Pfiesteria treatment caused a significant decrease in mean locomotor activity. In study 2, the neurobehavioral effects of the Pf 728 sample type were assessed in juvenile rats. Twenty-four day-old male and female rats were injected with 35,600 or 106,800 Pf-728 Pfiesteria cells per kilogram of rat body weight. As with adult females, the juvenile rats showed a significant impairment in radial-arm maze choice accuracy. No changes in locomotor activity or the FOB were detected in the

  8. Comparison of drug and cell-based delivery: engineered adult mesenchymal stem cells expressing soluble tumor necrosis factor receptor II prevent arthritis in mouse and rat animal models.

    PubMed

    Liu, Linda N; Wang, Gang; Hendricks, Kyle; Lee, Keunmyoung; Bohnlein, Ernst; Junker, Uwe; Mosca, Joseph D

    2013-05-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease with unknown etiology where tumor necrosis factor-α (TNFα) plays a critical role. Etanercept, a recombinant fusion protein of human soluble tumor necrosis factor receptor II (hsTNFR) linked to the Fc portion of human IgG1, is used to treat RA based on the rationale that sTNFR binds TNFα and blocks TNFα-mediated inflammation. We compared hsTNFR protein delivery from genetically engineered human mesenchymal stem cells (hMSCs) with etanercept. Blocking TNFα-dependent intercellular adhesion molecule-1 expression on transduced hMSCs and inhibition of nitric oxide production from TNFα-treated bovine chondrocytes by conditioned culture media from transduced hMSCs demonstrated the functionality of the hsTNFR construction. Implanted hsTNFR-transduced mesenchymal stem cells (MSCs) reduced mouse serum circulating TNFα generated from either implanted TNFα-expressing cells or lipopolysaccharide induction more effectively than etanercept (TNFα, 100%; interleukin [IL]-1α, 90%; and IL-6, 60% within 6 hours), suggesting faster clearance of the soluble tumor necrosis factor receptor (sTNFR)-TNFα complex from the animals. In vivo efficacy of sTNFR-transduced MSCs was illustrated in two (immune-deficient and immune-competent) arthritic rodent models. In the antibody-induced arthritis BalbC/SCID mouse model, intramuscular injection of hsTNFR-transduced hMSCs reduced joint inflammation by 90% compared with untransduced hMSCs; in the collagen-induced arthritis Fischer rat model, both sTNFR-transduced rat MSCs and etanercept inhibited joint inflammation by 30%. In vitro chondrogenesis assays showed the ability of TNFα and IL1α, but not interferon γ, to inhibit hMSC differentiation to chondrocytes, illustrating an additional negative role for inflammatory cytokines in joint repair. The data support the utility of hMSCs as therapeutic gene delivery vehicles and their potential to be used in alleviating inflammation

  9. Endotoxemia in newborn rats attenuates acute pancreatitis at adult age.

    PubMed

    Jaworek, J; Konturek, S J; Macko, M; Kot, M; Szklarczyk, J; Leja-Szpak, A; Nawrot-Porabka, K; Stachura, J; Tomaszewska, R; Siwicki, A; Pawlik, W W

    2007-03-01

    Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar

  10. 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.

  11. Contextual fear conditioning differs for infant, adolescent, and adult rats

    PubMed Central

    Esmorís-Arranz, Francisco J.; Méndez, Cástor; Spear, Norman E.

    2009-01-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian conditioned suppression. When a discrete auditory conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role. PMID:18343048

  12. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain.

    PubMed

    Asato, F; Butler, M; Blomberg, H; Gordh, T

    2000-03-01

    We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

  13. Plexin a4 expression in adult rat cranial nerves.

    PubMed

    Gutekunst, Claire-Anne; Gross, Robert E

    2014-11-01

    PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2. PlexinA4 is the latest member of the PlexinA subfamily to be identified. In previous studies, we described the expression of PlexinA4 in the brain and spinal cord of the adult rat. Here, antibodies to PlexinA4 were used to reveal immunolabeling in most of the cranial nerve surveyed. Labeling was found in the olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibulocochlear, glossopharyngeal, vagus, and hypoglossal nerves. This is the first detailed description of the cellular and subcellular distribution of PlexinA4 in the adult cranial nerves. The findings will set the basis for future studies on the potential role of PlexinA4 in regeneration and repair of the adult central and peripheral nervous system.

  14. 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.

  15. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

    PubMed Central

    Lensu, Sanna; Ahtiainen, Juha P.; Johansson, Petra P.; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

    2016-01-01

    Key points Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.Our results confirm that sustained aerobic exercise is key in improving AHN. Abstract Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength

  16. Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

    PubMed

    Lu, Qi; Jiang, Cuiping; Zhang, Jiping

    2016-02-01

    Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time.

  17. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    PubMed

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

  18. Wnt Expression in the Adult Rat Subventricular Zone After Stroke

    PubMed Central

    Morris, Daniel C.; Zhang, Zheng Geng; Wang, Ying; Zhang, Rui Lan; Greg, Sara; Liu, Xian Shuang; Chopp, Michael

    2007-01-01

    Introduction: In the adult brain, neurogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle. During development, the Wnt pathways contribute to stem cell maintenance and promote neurogenesis. We hypothesized that the Wnt family genes are expressed in neural progenitor cells of the non-ischemic and ischemic SVZ of the adult rodent brain after middle cerebral artery (MCA) occlusion. Methods: Non-ischemic and ischemic cultured SVZ cells and a single population of non-ischemic and ischemic SVZ cells isolated by laser capture microdisection (LCM) were analyzed for Wnt pathway expression using real-time RT-PCR and immunostaining. Results: The number of neurospheres increased significantly (p<0.05) in SVZ cells derived from ischemic (32 ±4.7/rat) compared with the number in non-ischemic SVZ cells (18 ± 3/rat). Wnt family gene mRNA levels were detected in SVZ cells isolated from both cultured and LCM SVZ cells, however there was no upregulation between non-ischemic and ischemic SVZ cells. Immunostaining on brain sections also demonstrated no upregulation of Wnt pathway protein between ischemic and non-ischemic SVZ cells. Conclusions: Expression of the Wnt family genes in SVZ cells suggests that the Wnt pathway may be involved in neurogenesis in the adult brain. However, ischemia does not upregulate Wnt family gene expression. PMID:17400378

  19. Ih without Kir in Adult Rat Retinal Ganglion Cells

    PubMed Central

    Lee, Sherwin C.; Ishida, Andrew T.

    2011-01-01

    Antisera directed against hyperpolarization-activated mixed-cation (“Ih”) and K+ (“Kir”) channels bind to some somata in the ganglion cell layer of rat and rabbit retina. Additionally, the termination of hyperpolarizing current injections can trigger spikes in some cat retinal ganglion cells, suggesting a rebound depolarization due to activation of Ih. However, patch-clamp studies have reported that rat ganglion cells lack inward rectification, or present an inwardly rectifying K+ current. We therefore tested whether hyperpolarization activates Ih in dissociated, adult rat retinal ganglion cell somata. We report here that while we found no inward rectification in some cells, and a Kir-like current in a few cells, hyperpolarization activated Ih in roughly 75% of the cells we recorded from in voltage clamp. We show that this current is blocked by Cs+ or ZD7288 and only slightly reduced by Ba2+, that the current amplitude and reversal potential are sensitive to extracellular Na+ and K+, and that we found no evidence of Kir in cells presenting Ih. In current clamp, injecting hyperpolarizing current induced a slowly relaxing membrane hyperpolarization that rebounded to a few action potentials when the hyperpolarizing current was stopped; both the membrane potential relaxation and rebound spikes were blocked by ZD7288. These results provide the first measurement of Ih in mammalian retinal ganglion cells, and indicate that the ion channels of rat retinal ganglion cells may vary in ways not expected from previous voltage and current recordings. PMID:17488978

  20. Experimental induction of corpora amylacea in adult rat brain.

    PubMed

    Schipper, H M

    1998-10-01

    Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.

  1. Challenges of animal models in SCI research: Effects of pre-injury task-specific training in adult rats before lesion.

    PubMed

    May, Zacnicte; Fouad, Karim; Shum-Siu, Alice; Magnuson, David S K

    2015-09-15

    A rarely explored subject in animal research is the effect of pre-injury variables on behavioral outcome post-SCI. Low reporting of such variables may underlie some discrepancies in findings between laboratories. Particularly, intensive task-specific training before a SCI might be important, considering that sports injuries are one of the leading causes of SCI. Thus, individuals with SCI often underwent rigorous training before their injuries. In the present study, we asked whether training before SCI on a grasping task or a swimming task would influence motor recovery in rats. Swim pre-training impaired recovery of swimming 2 and 4 weeks post-injury. This result fits with the idea of motor learning interference, which posits that learning something new may disrupt learning of a new task; in this case, learning strategies to compensate for functional loss after SCI. In contrast to swimming, grasp pre-training did not influence grasping ability after SCI at any time point. However, grasp pre-trained rats attempted to grasp more times than untrained rats in the first 4 weeks post-injury. Also, lesion volume of grasp pre-trained rats was greater than that of untrained rats, a finding which may be related to stress or activity. The increased participation in rehabilitative training of the pre-trained rats in the early weeks post-injury may have potentiated spontaneous plasticity in the spinal cord and counteracted the deleterious effect of interference and bigger lesions. Thus, our findings suggest that pre-training plays a significant role in recovery after CNS damage and needs to be carefully controlled for.

  2. Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

    PubMed Central

    Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms. PMID:25738800

  3. 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

  4. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    PubMed

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  5. Fructose-1,6-bisphosphatase from young and adult rats.

    PubMed

    Klefenz, H F; Rockstein, M

    1976-07-01

    Fructose-1,6-bisphosphatase (E.C. 3.1.3.11) was purified from the livers of young (69-86 days) and adult (370-386 days) Fisher rats. The enzyme preparations were examined for increasing amounts of missynthesized proteins by means of heat-inactivation as well as for differences in regulatory properties. No significant difference with respect to the fraction of rapidly heat-inactivated enzyme or Km- and Ki-values was found. These results do not support the hypothesis that error accumulation resulting in an error catastrophe is a general phenomenon underlying senescence and death.

  6. 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.

  7. 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

  8. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

    EPA Pesticide Factsheets

    behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil.Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP)Molecular changes induced by LTPThis dataset is associated with the following publication:Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

  9. A new protocol for cultivation of predegenerated adult rat Schwann cells.

    PubMed

    Pietrucha-Dutczakv, Marita; Marcol, Wiesław; Francuz, Tomasz; Gołka, Dariusz; Lewin-Kowalik, Joanna

    2014-09-01

    The purpose of this study was to optimize the methodology of cultivation of predegenerated Schwann cells (SCs). SCs were isolated from 7-day-predegenerated sciatic nerves of adult rats. We applied commercially available culture medium for cultivation of endothelial cells endothelial cell culture medium (EBM-2) instead of Dulbecco's Modified Eagle's Medium commonly used to culture adult Schwann cells. Additionally, cell culture medium was supplemented with factors specifically supporting SCs growth as: bovine pituitary extract (5 μg/ml), heregulin (40 ng/ml) and insulin (2.5 ng/ml). Similarly to the reports of others authors, we did not observe any beneficial effects of Forskolin application, so we didn't supplement our medium with it. Cell culture purity was determined by counting the ratio of GFAP, N-Cadherin and NGFR p75-positive cells to total number of cells. About 94-97 % of cells were confirmed as Schwann cells. As a result, we obtained sufficient number and purity of Schwann cells to be applied in different experimental models in rats. EBM-2 medium coated with fibronectin was the best for cultivation of adult rat Schwann cells.

  10. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    PubMed Central

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-01-01

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms. PMID:24806340

  11. Daily patterns of ethanol drinking in adolescent and adult, male and female, high alcohol drinking (HAD) replicate lines of rats.

    PubMed

    Dhaher, Ronnie; McConnell, Kathleen K; Rodd, Zachary A; McBride, William J; Bell, Richard L

    2012-10-01

    The rationale for our study was to determine the pattern of ethanol drinking by the high alcohol-drinking (HAD) replicate lines of rats during adolescence and adulthood in both male and female rats. Rats were given 30 days of 24 h free-choice access to ethanol (15%, v/v) and water, with ad lib access to food, starting at the beginning of adolescence (PND 30) or adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day with a "lickometer" set-up. The results indicated that adolescent HAD-1 and HAD-2 males consumed the greatest levels of ethanol and had the most well defined ethanol licking binges among the age and sex groups with increasing levels of ethanol consumption throughout adolescence. In addition, following the first week of adolescence, male and female HAD-1 and HAD-2 rats differed in both ethanol consumption levels and ethanol licking behavior. Adult HAD-1 male and female rats did not differ from one another and their ethanol intake or licking behaviors did not change significantly over weeks. Adult HAD-2 male rats maintained a relatively constant level of ethanol consumption across weeks, whereas adult HAD-2 female rats increased ethanol consumption levels over weeks, peaking during the third week when they consumed more than their adult male counterparts. The results indicate that the HAD rat lines could be used as an effective animal model to examine the development of ethanol consumption and binge drinking in adolescent male and female rats providing information on the long-range consequences of adolescent alcohol drinking.

  12. Experimental mammary carcinogenesis - Rat models.

    PubMed

    Alvarado, Antonieta; Faustino-Rocha, Ana I; Colaço, Bruno; Oliveira, Paula A

    2017-03-15

    Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

  13. 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.

  14. Amodiaquine-induced reproductive toxicity in adult male rats.

    PubMed

    Niu, Yan-Ru; Wei, Bing; Chen, Bi; Xu, Li-Hua; Jing, Xia; Peng, Cai-Ling; Ma, Tian-Zhong

    2016-02-01

    Amodiaquine (AQ) is routinely prescribed as an anti-malarial drug. Here, we evaluated AQ-induced toxicity in the male reproductive system. Eighty adult male Sprague-Dawley rats were randomly divided into four groups that received distilled water (control) or daily doses of 5 mg/kg body weight, 10 mg/kg, or 15 mg/kg AQ for 2 weeks. Testes morphology was analyzed using hematoxylin-and-eosin staining, terminal dUTP nicked-end labeling (TUNEL), and immunostaining whereas protein expression was determined by Western blotting. AQ dose-dependently led to abnormal spermatogenesis. Disruption of the blood-testis barrier and increased germ cell apoptosis were observed in all three AQ-treated groups. Interestingly, AQ-induced damage of spermatogenesis recovered over time, based on the survival of promyelocytic leukemia zinc-finger (PLZF)-positive, undifferentiated spermatogonia. Serum levels of luteinizing hormone and testosterone, as well as testicular testosterone levels, were not significantly altered in AQ-treated groups compared with controls. Collectively, our study suggests that AQ exerts substantial acute side effects on the reproductive systems of adult male rats by inducing the apoptosis of differentiating spermatogenic cells and disruption of blood-testis barrier function.

  15. Age and sex differences in reward behavior in adolescent and adult rats.

    PubMed

    Hammerslag, Lindsey R; Gulley, Joshua M

    2014-05-01

    Compared to adults, adolescents are at heightened risk for drug abuse and dependence. One of the factors contributing to this vulnerability may be age-dependent differences in reward processing, with adolescents approaching reward through stimulus-directed, rather than goal-directed, processes. However, the empirical evidence for this in rodent models of adolescence, particularly those that investigate both sexes, is limited. To address this, male and female rats that were adolescents (P30) or adults (P98) at the start of the experiment were trained in a Pavlovian approach (PA) task and were subsequently tested for the effects of reward devaluation, extinction, and re-acquisition. We found significant interactions between age and sex: females had enhanced acquisition of PA and poorer extinction, relative to males, while adolescents and females were less sensitive to reward devaluation than male adults. These results suggest that females and adolescents exhibit reward behavior that is more stimulus-directed, rather than goal-directed.

  16. Development of PBPK Models for Gasoline in Adult and ...

    EPA Pesticide Factsheets

    Concern for potential developmental effects of exposure to gasoline-ethanol blends has grown along with their increased use in the US fuel supply. Physiologically-based pharmacokinetic (PBPK) models for these complex mixtures were developed to address dosimetric issues related to selection of exposure concentrations for in vivo toxicity studies. Sub-models for individual hydrocarbon (HC) constituents were first developed and calibrated with published literature or QSAR-derived data where available. Successfully calibrated sub-models for individual HCs were combined, assuming competitive metabolic inhibition in the liver, and a priori simulations of mixture interactions were performed. Blood HC concentration data were collected from exposed adult non-pregnant (NP) rats (9K ppm total HC vapor, 6h/day) to evaluate performance of the NP mixture model. This model was then converted to a pregnant (PG) rat mixture model using gestational growth equations that enabled a priori estimation of life-stage specific kinetic differences. To address the impact of changing relevant physiological parameters from NP to PG, the PG mixture model was first calibrated against the NP data. The PG mixture model was then evaluated against data from PG rats that were subsequently exposed (9K ppm/6.33h gestation days (GD) 9-20). Overall, the mixture models adequately simulated concentrations of HCs in blood from single (NP) or repeated (PG) exposures (within ~2-3 fold of measured values of

  17. Advances on genetic rat models of epilepsy.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  18. Advances on genetic rat models of epilepsy

    PubMed Central

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  19. 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

  20. Contractile force measured in unskinned isolated adult rat heart fibres.

    PubMed

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  1. Acute toxicity of pesticides in adult and weanling rats.

    PubMed

    Gaines, T B; Linder, R E

    1986-08-01

    LD50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Thirty-six of the chemicals were also tested by the oral route in one sex of weanlings. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and four tested by the dermal route (bufencarb, chlordimeform, dichlofenthion, leptophos) were more toxic to females than to males whereas famphur and 2,4,5-T (oral route) were less toxic to females. Eighteen of the test chemicals were more toxic to the adult than to the weanling and four compounds (leptophos, methidathion, pyrazon, and sulfoxide) were more toxic to the weanling. In additional studies the variability of the LD50 value over a 1-year period was examined for two typical insecticides. Six consecutive bimonthly oral LD50 determinations for parathion and DDT in adults of both sexes indicated that the LD50 values were little affected by the time of year that the tests were done.

  2. Birth insult alters ethanol preference in the adult rat.

    PubMed

    Boksa, P

    1998-05-08

    While genetic factors clearly play a role in regulating ethanol intake, the present study considered the possibility that early environmental factors which influence central nervous system development and long-term function might also alter ethanol intake. The specific aim of the study was to test whether alterations in birth condition, namely Caesarean section (C-section) birth and C-section birth with an added period of global anoxia, can affect subsequent ethanol preference in the adult rat. At 5 months of age, groups of experimental and vaginally born control rats were offered free choice between drinking water or various concentrations of ethanol (1-10% v/v) in water across 36 days of testing. Rats that had been born by C-section with 10 or 15 min of added global anoxia showed significant reductions in ethanol preference scores, in comparison to vaginally born controls. For the 10-min anoxia group, ethanol intake was decreased, water intake was increased and total fluid intake remained unchanged relative to values for vaginally born controls, across the entire test period. Although total fluid intake by the 15-min anoxia group also did not differ from that of vaginally born controls, the decreased ethanol preference scores in the 15-min anoxia group were mainly due to increased water intake during some test periods and a combination of reduced ethanol intake and increased water intake during others. Animals born by rapid C-section alone, with no added period of global anoxia, showed reduced ethanol preference only during a few early periods of testing, a much less pronounced effect than that observed for animals with added global anoxia. When animals were given the choice between drinking water vs. solutions of sucrose or NaCl, no group differences due to birth condition were found on measures of sucrose or NaCl preference. Together with reduced ethanol preference, the 10-min anoxia group showed a transient depression of locomotor activity in response to a low

  3. 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

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

    PubMed

    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

  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. Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters.

    PubMed

    Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

    2007-04-15

    Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.

  7. A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

    EPA Science Inventory

    The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

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

    PubMed Central

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

    2016-01-01

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

  9. Bupropion attenuates methamphetamine self-administration in adult male rats.

    PubMed

    Reichel, Carmela M; Murray, Jennifer E; Grant, Kathleen M; Bevins, Rick A

    2009-02-01

    Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg i.p.) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025-0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific.

  10. FACS purification of immunolabeled cell types from adult rat brain.

    PubMed

    Guez-Barber, Danielle; Fanous, Sanya; Harvey, Brandon K; Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G; Picciotto, Marina R; Hope, Bruce T

    2012-01-15

    Molecular analysis of brain tissue is greatly complicated by having many different classes of neurons and glia interspersed throughout the brain. Fluorescence-activated cell sorting (FACS) has been used to purify selected cell types from brain tissue. However, its use has been limited to brain tissue from embryos or transgenic mice with promoter-driven reporter genes. To overcome these limitations, we developed a FACS procedure for dissociating intact cell bodies from adult wild-type rat brains and sorting them using commercially available antibodies against intracellular and extracellular proteins. As an example, we isolated neurons using a NeuN antibody and confirmed their identity using microarray and real time PCR of mRNA from the sorted cells. Our FACS procedure allows rapid, high-throughput, quantitative assays of molecular alterations in identified cell types with widespread applications in neuroscience.

  11. Chordin and noggin expression in the adult rat trigeminal nuclei.

    PubMed

    Hayashi, Yutaro; Mikawa, Sumiko; Masumoto, Kazuma; Katou, Fuminori; Sato, Kohji

    2016-12-01

    Bone morphogenetic proteins (BMP) exert its biological functions by interacting with membrane bound receptors. However, functions of BMPs are also regulated in the extracellular space by secreted antagonistic regulators, such as chordin and noggin. Although the deep involvement of BMP signaling in the development and functions of the trigeminal nuclei has been postulated, little information is available for its expression in the trigeminal nuclei. We, thus, investigated chordin and noggin expression in the adult rat trigeminal nuclei using immunohistochemistry. Chordin and noggin were intensely expressed throughout the trigeminal nuclei. In addition, interesting differences are observed between chordin expression and noggin expression. For example, chordin prefers dendritic expression than noggin, suggesting that chordin is involved in the regulation of dendritic morphology and synaptic homeostasis. Furthermore, chordin and noggin were differentially expressed in the neuropil of the trigeminal nuclei. Since BMP signaling is known to play a pivotal role to make precise neural network, theses differences might be important to keep precise interneuronal connections by regulating local BMP signaling intensity in each region. Interestingly, we also detected chordin and noggin expression in axons of the trigeminal nerves. These data indicate that chordin and noggin play pivotal roles also in the adult trigeminal system.

  12. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMOKINETICS (PBPK) MODEL TO COMPARE DIFFERENCES IN DISPOSITION OF TRICHLOROETHYLENE (TCE) IN ADULT VERSUS ELDERLY RATS

    EPA Science Inventory

    Due to the increasing number of elderly in the American Population, the question as to whether the aged have different susceptibility to environmental contaminants needs to be addressed. Physiologically based pharmacokinetic (PBPK) models are used to extrapolate between rodents (...

  13. Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

    PubMed Central

    Udoekwere, Ubong I.; Oza, Chintan S.

    2016-01-01

    Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with “poor” and “high weight support” groupings. A total of 35% of rats initially classified as “poor” were able to increase their weight-supported step measures to a level considered “high weight support” after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. SIGNIFICANCE STATEMENT Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal

  14. Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development.

    PubMed

    Pittet, Florent; Babb, Jessica A; Carini, Lindsay; Nephew, Benjamin C

    2017-04-01

    We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

  15. Chronic exposure of adult rats to low doses of methylmercury induced a state of metabolic deficit in the somatosensory cortex.

    PubMed

    Kong, Hang-Kin; Wong, Ming-Hung; Chan, Hing-Man; Lo, Samuel Chun-Lap

    2013-11-01

    Because of the ever-increasing bioaccumulation of methylmercury (MeHg) in the marine food chain, human consumers are exposed to low doses of MeHg continually through seafood consumption. Epidemiological studies strongly suggest that chronic prenatal exposure to nanomolar of MeHg has immense negative impacts on neurological development in neonates. However, effects of chronic exposure to low doses (CELDs) of MeHg in adult brains on a molecular level are unknown. The current study aims to investigate the molecular effects of CELD of MeHg on adult somatosensory cortex in a rat model using proteomic techniques. Young adult rats were fed with a low dose of MeHg (40 μg/kg body weight/day) for a maximum of 12 weeks. Whole proteome expression of the somatosensory cortex (S1 area) of normal rats and those with CELD to MeHg were compared. Levels of MeHg, total calcium, adenosine triphosphate (ATP), and pyruvate were also measured. Comparative proteomic studies of the somatosensory cortexes revealed that 94 proteins involved in the various metabolic processes (including carbohydrate metabolism, generation of precursors for essential metabolites, energy, proteins, cellular components for morphogenesis, and neurotransmission) were down-regulated. Consequently, levels of important end products of active metabolism including ATP, pyruvate, and total calcium were also found to be significantly reduced concomitantly. Our results showed that CELD of MeHg induced a state of metabolic deficit in the somatosensory cortex of adult rats.

  16. Behavioral differences between late preweanling and adult female Sprague-Dawley rat exploration of animate and inanimate stimuli and food.

    PubMed

    Smith, Kiersten S; Morrell, Joan I

    2011-03-01

    The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied stimuli, including inanimate objects systematically varied in size and interactive properties, biological stimuli, and food. Preweanlings were faster to initiate specific stimulus exploration and were more interactive with most specific stimuli than adults; the magnitude of these preweanling-adult quantitative differences ranged from fairly small to very large depending upon the stimulus. In contrast, preweanlings were adult-like in their interaction with food and prey. Preweanling response to some stimuli, for example to live pups, was qualitatively different from that of adults; the preweanling behavioral repertoire was characterized by pup-seeking while the adult response was characterized by pup-avoidance. The specific stimulus interactions of preweanlings were less impacted than those of adults by the time of day of testing and placement of a stimulus in an anxiety-provoking location. The impact of novelty was stimulus dependent. The differences in interactions of preweanlings versus adults with specific stimuli suggests that CNS systems underlying these behavior patterns are at different stages of immaturity at PND 18 such that there may be an array of developmental trajectories for various categories of specific stimuli. These data provide a basis for the use of the preweanling as a preclinical model for understanding and medicating human disorders during development that are characterized by dysfunctional interactions with specific stimuli.

  17. Photon and electron absorbed fractions calculated from a new tomographic rat model

    NASA Astrophysics Data System (ADS)

    Peixoto, P. H. R.; Vieira, J. W.; Yoriyaz, H.; Lima, F. R. A.

    2008-10-01

    This paper describes the development of a tomographic model of a rat developed using CT images of an adult male Wistar rat for radiation transport studies. It also presents calculations of absorbed fractions (AFs) under internal photon and electron sources using this rat model and the Monte Carlo code MCNP. All data related to the developed phantom were made available for the scientific community as well as the MCNP inputs prepared for AF calculations in that phantom and also all estimated AF values, which could be used to obtain absorbed dose estimates—following the MIRD methodology—in rats similar in size to the presently developed model. Comparison between the rat model developed in this study and that published by Stabin et al (2006 J. Nucl. Med. 47 655) for a 248 g Sprague-Dawley rat, as well as between the estimated AF values for both models, has been presented.

  18. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.

    PubMed

    Yin, Fei; Guo, Li; Meng, Chun-yang; Liu, Ya-juan; Lu, Ri-feng; Li, Peng; Zhou, Yu-bo

    2014-05-02

    It is unknown whether transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can repair spinal cord ischemia-reperfusion injury (SCII) in a rat model through an anti-apoptotic effect. Adult rats were divided into untreated or sham-operated controls, untreated models of SCII (uSCII) and BM-MSC-transplanted models of SCII (tSCII; labeled with CM-Dill transplanted at 1 h and 24 h after reperfusion). According to evaluation of hind-limb motor function, the motor functions of tSCII rats were significantly better than those of uSCII rats by the seventh day. H&E and TUNEL staining showed that the spinal cords of uSCII rats contained damaged neural cells with nuclear pyknosis and congestion of blood vessels, with a high percentage of apoptotic neural cells, while the spinal cords of tSCII rats were nearly normal with significantly fewer apoptotic neural cells. Immunohistochemistry and double immunofluorescence staining revealed that in tSCII rats CASP3 and neurofilament-H (NF-H) levels were 14.57% and 174% those of uSCII rats, respectively, and in tSCII rats the ratio of BAX to BCL2 was reduced by nearly 50%. The differentiation of transplanted CM-Dil-labeled BM-MSCs into neurons and astrocytes was observed in the spinal cords of the tSCII rats under laser scanning confocal microscopy. These results showed that transplantation of BM-MSCs improved functional recovery after SCII via anti-apoptosis.

  19. Transformation of adult rat cardiac myocytes in primary culture.

    PubMed

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  20. Hindlimb Stretching Alters Locomotor Function Post-Spinal Cord Injury in the Adult Rat

    PubMed Central

    Caudle, Krista L.; Atkinson, Darryn A.; Brown, Edward H.; Donaldson, Katie; Seibt, Erik; Chea, Tim; Smith, Erin; Chung, Karianne; Shum-Siu, Alice; Cron, Courtney C.; Magnuson, David S. K.

    2014-01-01

    Background Stretching is a widely accepted standard-of-care therapy following spinal cord injury that has not been systematically studied in animal models. Objective To investigate the influence of a daily stretch-based physical therapy program on locomotor recovery in adult rats with moderate T9 contusive SCI. Methods A randomized treatment and control study of stretching in an animal model of acute spinal cord injury (SCI). Moderate spinal cord injuries were delivered with the NYU Impactor. Daily stretching (30 min./day, 5 days/wk for 8 wks) was provided by a team of animal handlers. Hindlimb function was assessed using the BBB Open Field Locomotor Scale and kinematically. Passive range-of-motion for each joint was determined weekly using a goniometer. Results Declines in hindlimb function during overground stepping were observed for the first 4 weeks. BBB scores improved weeks 5–10 but remained below the control group. Stretched animals had significant deficits in knee passive ROM starting at week 4 and for the duration of the study. Kinematic assessment showed decreased joint excursion during stepping that partially recovered beginning at week 5. Conclusion Stretch-based therapy significantly impaired functional recovery in adult rats with a moderate contusive SCI at T10. The negative impact on function was greatest acutely, but persisted even after the stretching ceased at 8 weeks post-injury. PMID:25106555

  1. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

    PubMed

    Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

    2016-01-01

    Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.

  2. Expression of gonadotropin-releasing hormone receptor in cerebral cortical neurons of embryos and adult rats.

    PubMed

    Quintanar, J Luis; Salinas, Eva; González, Rodolfo

    2007-01-03

    Mammalian gonadotropin-releasing hormone (GnRH) was initially isolated from hypothalamus and its receptor from anterior pituitary, although extrapituitary GnRH receptors have been reported. The aim of the present study was to investigate whether GnRH receptor and its mRNA are expressed in cerebral cortical neurons of rat embryos and adult rats using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The immunohistochemistry and RT-PCR analysis showed expression of GnRH receptor and presence of its mRNA, in both cerebral cortical neurons of rat embryos and cerebral cortical tissues of adult rats. Additional experiments showed a decrease in the receptor mRNA expression when cultured neurons of rat embryos were treated with GnRH. It is possible that the presence of GnRH receptors in cortical neurons of rat may be involved in other physiological roles such as neurohormone or neuromodulator.

  3. Role Models - Peers or Adults.

    ERIC Educational Resources Information Center

    Hawkes, F. J.

    Proceeding on the assumption that humans learn behaviors by imitating the behavior of others, the author is concerned with the appropriate behavioral models needed in dealing with delinquent female adolescents in a group situation. Three potential models are discussed: (1) the group leader or leaders; (2) the group members; and (3) the invited…

  4. PBPK MODELING OF DELTAMETHRIN IN RATS

    EPA Science Inventory

    The pyrethroid pesticide deltamethrin is cleared nearly twice as rapidly in human liver microsomes compared to rat liver microsomes. A species difference such as this could influence the toxic potency of deltamethrin between rats and humans. PBPK modeling is a tool that can be ut...

  5. Juvenile but not adult methamphetamine exposure improves performance in the Morris Water Maze in male rats.

    PubMed

    Moenk, Michael D; Matuszewich, Leslie

    2012-06-01

    Early exposure to psychostimulants has been found to lead to long-lasting effects on cognitive processes. Our lab has previously reported that juvenile male rats administered methamphetamine showed improved performance in a spatial navigation task when tested in adulthood (McFadden and Matuszewich, 2007). What is not known, however, is if these effects are specific to the developing rat, or if a similar methamphetamine protocol given to adult rats would lead to an equally beneficial long-term change in spatial cognition. In the current study, male rats were given 1 daily injection of 2mg/kg methamphetamine or saline for 15 days during either preadolescence (PD20-34) or adulthood (PD70-84). Approximately 45 days after treatment, all rats then underwent 5 days of place training in the Morris water maze at a time when juvenile rats reached adulthood. Similar to previous findings, juvenile rats exposed to repeated methamphetamine displayed shorter latencies and distances to reach the platform throughout training compared to saline-treated rats. The juvenile rats treated with methamphetamine also swam shorter distances and had faster latencies to the hidden platform compared to adult methamphetamine-treated rats. There were no significant differences in rats treated in adulthood with methamphetamine compared to saline-treated rats. Likewise, there were no effects of prior methamphetamine treatment or age on matching-to-place trials or visible platform trials. Overall, the results show that repeated methamphetamine exposure can selectively improve spatial learning in adult male rats when administered during preadolescence, but does not significantly affect spatial learning when administered in adulthood. Furthermore, the current findings demonstrate the unique susceptibility of the developing brain to drugs that modulate dopaminergic activity, as well as the long-term behavioral impact of exposure at critical ages.

  6. Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.

    PubMed

    Fan, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Xue, Jing-Ling; Wang, Fei-Fei; Zhang, Li; Yan, You-E

    2016-11-01

    The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.

  7. In vivo and in vitro dermal penetration of 2,4,5,2 prime ,4 prime , 5 prime -hexachlorobiphenyl in young and adult rats

    SciTech Connect

    Shah, P.V.; Sumler, M.R. ); Fisher, H.L.; Hall, L.L. )

    1989-10-01

    Penetration of 2,4,5,2{prime},4{prime},5{prime}-({sup 14}C)hexachlorobiphenyl (HCB) through skin of young (33 days) and adult (82 days) female Fischer 344 rats was determined in vivo and by two in vitro methods. In vivo dermal penetration at 120 hr was 45% in young and 43% in adults. At 72 hr in vivo dermal penetration was 35% in young and 26% in adults compared to 1.5% for young and 1.0% for adult as measured with a continuous flow in vitro system and 2.9% for young and 1.9% for adults as measured with a static in vitro system. Most of the dermally absorbed HCB remained in the body as only 4.9 and 2.6% of that absorbed was excreted by young and adult rats, respectively, at the end of 120 hr. Significant differences in dermal penetration and kinetics of HCB between young and adult female rats were observed. The elimination of ECB-derived material was approximately six times higher in feces than in urine. A physiological pharmacokinetic model was fitted to the organ and tissue radioactivity distribution data. Parameters in the model determined from dermal dosing of female Fischer 344 rats were in reasonable agreement with those reported in the literature for adult male Sprague-Dawley rats (iv dose). The rate constant for dermal penetration was 0.83 {times} 10{sup {minus}4} min{sup {minus}1} for adults and 0.96 {times} 10{sup {minus}4} min{sup {minus}1} for young. The delay or lag time parameter for dermal penetration was 4.4 hr in adults and 1.1 hr in young.

  8. Juvenile stress potentiates aversive 22-kHz ultrasonic vocalizations and freezing during auditory fear conditioning in adult male rats.

    PubMed

    Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Wöhr, Markus

    2012-09-01

    Traumatic experiences that occur during adolescence can render individuals vulnerable to mood and anxiety disorders. A model in juvenile rats (age: 27-29 days) was developed previously to study the long-term effects of adolescent stress exposure on behaviour and physiology. This paradigm, termed juvenile stress, involves subjecting juvenile rats to different stressors on consecutive days over a 3-day period. Here, we investigated the effects of the juvenile stress paradigm on freezing behaviour and aversive 22-kHz ultrasonic vocalizations (USVs) during auditory fear conditioning in adult male rats (age: 68-90 days). We found that rats previously subjected to juvenile stress increased aversive 22-kHz USVs (total calls and time spent calling) compared with controls during fear-conditioning training. The acoustic USV parameters between control and juvenile stress rats were largely equivalent, including duration, peak frequency and amplitude. While rats did not differ in freezing behaviour during fear conditioning, juvenile stress rats exhibited greater cue-conditioned freezing upon testing 24 h later. Our results show that juvenile stress elicited different long-term changes in freezing and aversive USVs during fear conditioning. Furthermore, they highlight the importance of assessing USVs to detect experience-dependent differences between control and stress-exposed animals which are not detectable by measuring visible behaviour.

  9. Prenatal ethanol exposure impairs temporal ordering behaviours in young adult rats.

    PubMed

    Patten, Anna R; Sawchuk, Scott; Wortman, Ryan C; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R

    2016-02-15

    Prenatal ethanol exposure (PNEE) causes significant deficits in functional (i.e., synaptic) plasticity in the dentate gyrus (DG) and cornu ammonis (CA) hippocampal sub-regions of young adult male rats. Previous research has shown that in the DG, these deficits are not apparent in age-matched PNEE females. This study aimed to expand these findings and determine if PNEE induces deficits in hippocampal-dependent behaviours in both male and female young adult rats (PND 60). The metric change behavioural test examines DG-dependent deficits by determining whether an animal can detect a metric change between two identical objects. The temporal order behavioural test is thought to rely in part on the CA sub-region of the hippocampus and determines whether an animal will spend more time exploring an object that it has not seen for a larger temporal window as compared to an object that it has seen more recently. Using the liquid diet model of FASD (where 6.6% (v/v) ethanol is provided through a liquid diet consumed ad libitum throughout the entire gestation), we found that PNEE causes a significant impairment in the temporal order task, while no deficits in the DG-dependent metric change task were observed. There were no significant differences between males and females for either task. These results indicate that behaviours relying partially on the CA-region may be more affected by PNEE than those that rely on the DG.

  10. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature.

    PubMed

    Li, Qing-Quan; Qiao, Guan-Qun; Ma, Jun; Fan, Hong-Wei; Li, Ying-Bin

    2015-02-01

    The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  11. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

    PubMed

    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging.

  12. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin).

    PubMed

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2009-01-01

    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  13. Long-term consequences of neonatal fluoxetine exposure in adult rats.

    PubMed

    Ko, Meng-Ching; Lee, Lukas Jyuhn-Hsiarn; Li, Yang; Lee, Li-Jen

    2014-10-01

    Serotonin (5-HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)-type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late-gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX-exposed adult male rats exhibited reduced locomotor activity and depression-like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX-exposed rats. When the levels of 5-HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long-lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI-type antidepressants during pregnancy should be considered.

  14. Neonatal manipulation of oxytocin alters oxytocin levels in the pituitary of adult rats.

    PubMed

    Young, E; Carter, C S; Cushing, B S; Caldwell, J D

    2005-07-01

    The neuropeptide oxytocin (OT) and its OT antagonists (OTA) in infant rats affect their behavior as adults. In this study we attempted to determine whether treating rats on the day of birth (postnatal day 1) with OT or OTA would affect brain OT levels of these rats as adults. Rat pups were injected with OT (3 microg), OTA (0.3 microg) or saline vehicle ip on postnatal day 1. As 60-day-old adults, treated rats were killed, and the OT content in their medial preoptic areas (MPOAs), medial hypothalami (MH) and pituitaries were assayed. In females, treatment with OTA on postnatal day 1 significantly decreased pituitary OT levels as adults. In males, by contrast, treatment with OTA on postnatal day 1 resulted in increased pituitary OT levels when they become adults compared to male rats treated with OT on postnatal day 1. There were no significant effects of neonatal treatment on OT levels in either the MH or MPOA. Day 1 postnatal treatment with OT or OTA had a long-term sexually dimorphic effect on OT levels in the pituitary.

  15. Effects of morphine on thermal sensitivity in adult and aged rats.

    PubMed

    Morgan, Drake; Mitzelfelt, Jeremiah D; Koerper, Lorraine M; Carter, Christy S

    2012-06-01

    There are contradictory data regarding older individuals' sensitivity to pain stimulation and opioid administration. Adult (12-16 months; n = 10) and aged (27-31 months; n = 7) male F344xBN rats were tested in a thermal sensitivity procedure where the animal chooses to remain in one of two compartments with floors maintained at various temperatures ranging from hot (45°C) through neutral (30°C) to cold (15°C). Effects of morphine were determined for three temperature comparisons (ie, hot/neutral, cold/neutral, and hot/cold). Aged rats were more sensitive to cold stimulation during baseline. Morphine produced antinociception during hot thermal stimulation, but had no effect on cold stimulation. The antinociceptive (and locomotor-altering) effects of morphine were attenuated in aged rats. These data demonstrate age-related differences in baseline thermal sensitivity and responsiveness to opioids. Based on behavioral and physiological requirements of this procedure, it is suggested that thermal sensitivity may provide a relevant animal model for the assessment of pain and antinociception.

  16. Learning under stress in the adult rat is differentially affected by 'juvenile' or 'adolescent' stress.

    PubMed

    Tsoory, Michael; Richter-Levin, Gal

    2006-12-01

    Epidemiological studies suggest that childhood trauma is associated with a predisposition to develop both mood and anxiety disorders, while trauma during adolescence is associated mainly with anxiety disorders. We studied in the rat the long-term consequences of 'juvenile' stress, namely stress experienced in a period in which substantial remodelling occurs across species in stress-sensitive brain areas involved in emotional and learning processing. In adulthood, 'juvenile' stressed rats exhibited reduced exploration in a novel setting, and poor avoidance learning, with 41% learning mainly to escape while 28% exhibited learned helplessness-like behaviours. In adult rats that underwent 'adolescent' stress, learned helplessness-like behaviours were not evident, although decreased exploration and poor avoidance learning were observed. This suggests that in the prepubertal phase juvenility may constitute a stress-sensitive period. The results suggest that juvenile stress induces lasting impairments in stress-coping responses. The 'juvenile' stress model presented here may be of relevance to individuals' reported predisposition to anxiety and depression following childhood trauma, and their increased susceptibility only to anxiety disorders following adolescent stress.

  17. Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

    PubMed

    Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

    2014-08-01

    Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.

  18. 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

  19. [Transplantation of embryonic medulla oblongata into cerebella of adult rats].

    PubMed

    Nanami, T

    1989-01-01

    Pieces of medulla oblongata anlagen were dissected free from embryonic 13-20 day (E 13 to E 20) rat brain, and these were transplanted into the cerebellar vermis of adult rats (Fischer 344). After grafting, host animals survived for 4-9 months. Cytoarchitectonic organization of the graft and the relationship between host and graft were analyzed light microscopically in 34 animals using the Nissl and silver impregnation methods. Fine structures of the graft were analyzed in 4 animals using electron microscope. Grafts from E 13-14 donor tissue showed the highest survival rate (90%), which decreased as the donor embryonic age increased (i.e., E 15-16: 33%, E 17-20: 15%). In the surviving grafts, small (5-10 microns diameter), medium-sized (10-20 microns) and large (20-30 microns) neurons, whose cytoplasmic organelles appeared normal, were observed. Bundles of myelinated fibers traversed in every direction and neurons were often clustered, indicating characteristic features of the medulla oblongata. Electron microscopically, various types of synaptic formations were also observed. Degenerative profiles of nerve-fiber endings, containing dense bodies and lysosomal figures, were also seen. The degeneration seemed to be caused by the failure of their establishing connections with their proper targets in the host. In both the host tissue and the graft-host interface, neuronal processes apparently derived from the graft were frequently observed. Some axonal processes contained large-cored vesicles, and some dendritic processes were enlarged at their stalks and tips. Aberrant axon terminals of unmyelinated fibers in the host medullary layer were considered to be the graft origin. These fibers were always accompanied by prominent glial proliferation. There was no indication of forming myelinated fiber bundles that entered the host cerebellum from the donor tissue, although the former was the target of the latter. Cell bodies of host granule cells and oligodendroglia in the

  20. Differential effects of delta9-THC on learning in adolescent and adult rats.

    PubMed

    Cha, Young May; White, Aaron M; Kuhn, Cynthia M; Wilson, Wilkie A; Swartzwelder, H S

    2006-03-01

    Marijuana use remains strikingly high among young users in the U.S., and yet few studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in adolescents compared to adults. This study measured the effects of THC on male adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent (PD=30-32) and adult (PD=65-70) rats were treated acutely with 5.0 mg/kg THC or vehicle while trained on the spatial version of the water maze on five consecutive days. In Experiment 2, adolescent and adult rats were treated acutely with 2.5 or 10.0 mg/kg THC or vehicle while trained on either the spatial and non-spatial versions of the water maze. In Experiment 3, adolescent and adult rats were treated with 5.0 mg/kg THC or vehicle daily for 21 days, and were trained on the spatial and then the non-spatial versions of the water maze task four weeks later in the absence of THC. THC impaired both spatial and nonspatial learning more in adolescents than in adults at all doses tested. However, there were no long-lasting significant effects on either spatial or non-spatial learning in rats that had been previously exposed to THC for 21 days. This developmental sensitivity is analogous to the effects of ethanol, another commonly used recreational drug.

  1. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    PubMed

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

  2. Long-lasting alterations of hippocampal GABAergic neurotransmission in adult rats following perinatal Δ(9)-THC exposure.

    PubMed

    Beggiato, Sarah; Borelli, Andrea Celeste; Tomasini, Maria Cristina; Morgano, Lucia; Antonelli, Tiziana; Tanganelli, Sergio; Cuomo, Vincenzo; Ferraro, Luca

    2017-03-01

    The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored. To this purpose, pregnant rats were treated daily with Delta(9)-tetrahydrocannabinol (Δ(9)-THC; 5mg/kg) or its vehicle. Perinatal exposure to Δ(9)-THC induced a significant reduction (p<0.05) in basal and K(+)-evoked [(3)H]-GABA outflow of 90-day-old rat hippocampal slices. These effects were associated with a reduction of hippocampal [(3)H]-GABA uptake compared to vehicle exposed group. Perinatal exposure to Δ(9)-THC induced a significant reduction of CB1 receptor binding (Bmax) in the hippocampus of 90-day-old rats. However, a pharmacological challenge with either Δ(9)-THC (0.1μM) or WIN55,212-2 (2μM), similarly reduced K(+)-evoked [(3)H]-GABA outflow in both experimental groups. These reductions were significantly blocked by adding the selective CB1 receptor antagonist SR141716A. These findings suggest that maternal exposure to cannabinoids induces long-term alterations of hippocampal GABAergic system. Interestingly, previous behavioral studies demonstrated that, under the same experimental conditions as in the present study, perinatal cannabinoids exposure induced cognitive impairments in adult rats, thus resembling some effects observed in humans. Although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of hippocampus aminoacidergic transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of

  3. Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring.

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-08-01

    Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings

  4. Posttraumatic seizures and epilepsy in adult rats after controlled cortical impact.

    PubMed

    Kelly, Kevin M; Miller, Eric R; Lepsveridze, Eka; Kharlamov, Elena A; Mchedlishvili, Zakaria

    2015-11-01

    Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. Provoked class 3-5 seizures were recorded by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI of the right parietal cortex; none of the 7 animals demonstrated subsequent spontaneous convulsive seizures. Monitoring with video and/or video-EEG was performed on 128 animals at various time points 8-619 days beyond one week following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in 7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually characterized by an initial change in behavior (head raising or animal alerting) followed by motor arrest during an ictal discharge that consisted of high-amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz class 3-5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI-injured, 13 controls) underwent transcardial perfusion for gross and microscopic studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure-function relationships that underlie epileptogenesis and PTE.

  5. Age and Sex Differences in Reward Behavior in Adolescent and Adult Rats

    PubMed Central

    Hammerslag, Lindsey R.; Gulley, Joshua M.

    2016-01-01

    Compared to adults, adolescents are at heightened risk for drug abuse and dependence. One of the factors contributing to this vulnerability may be age-dependent differences in reward processing, with adolescents approaching reward through stimulus-directed, rather than goal-directed, processes. However, the empirical evidence for this in rodent models of adolescence, particularly those that investigate both sexes, is limited. To address this, male and female rats that were adolescents (P30) or adults (P98) at the start of the experiment were trained in a Pavlovian approach (PA) task and were subsequently tested for the effects of reward devaluation, extinction, and re-acquisition. We found significant interactions between age and sex: females had enhanced acquisition of PA and poorer extinction, relative to males, while adolescents and females were less sensitive to reward devaluation than male adults. These results suggest that females and adolescents exhibit reward behavior that is more stimulus-directed, rather than goal-directed. PMID:23754712

  6. Neonatal Androgen Exposure Causes Persistent Gut Microbiota Dysbiosis Related to Metabolic Disease in Adult Female Rats.

    PubMed

    Moreno-Indias, Isabel; Sánchez-Alcoholado, Lidia; Sánchez-Garrido, Miguel Ángel; Martín-Núñez, Gracia María; Pérez-Jiménez, Francisco; Tena-Sempere, Manuel; Tinahones, Francisco J; Queipo-Ortuño, María Isabel

    2016-12-01

    Alterations of gut microbiome have been proposed to play a role in metabolic disease, but the major determinants of microbiota composition remain ill defined. Nutritional and sex hormone challenges, especially during early development, have been shown to permanently alter adult female phenotype and contribute to metabolic disturbances. In this study, we implemented large-scale microbiome analyses to fecal samples from groups of female rats sequentially subjected to various obesogenic manipulations, including sex hormone perturbations by means of neonatal androgenization or adult ovariectomy (OVX), as a model of menopause, to establish whether these phenomena are related to changes in gut microbiota. Basic metabolic profiles concerning glucose/insulin homeostasis were also explored. The effects of the sex hormonal perturbations, either developmentally (androgenization) or in adulthood (OVX), clearly outshone the impact of nutritional interventions, especially concerning the gut microbiota profile. Notably, we observed a lower diversity in the androgenized group, with the highest Firmicutes to Bacteroidetes ratio, supporting the occurrence of durable alterations in gut microbiota composition, even in adulthood. Moreover, the elimination of adult ovarian secretions by OVX affected the richness of gut microbiota. Our data are the first to document the durable impact of sex steroid manipulations, and particularly early androgenization, on gut microbiota composition. Such dysbiosis is likely to contribute to the metabolic perturbations of conditions of obesity linked to gonadal dysfunction in the female.

  7. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  8. Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

    PubMed Central

    Li, Dongpeng; Ma, Shanshan; Guo, Dewei; Cheng, Tian; Li, Hongwei; Tian, Yi; Li, Jianbin; Guan, Fangxia; Yang, Bo; Wang, Jian

    2016-01-01

    Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague–Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID:26886755

  9. Different effects of vitamin D hormone treatment on depression-like behavior in the adult ovariectomized female rats.

    PubMed

    Fedotova, Julia; Dudnichenko, Tatyana; Kruzliak, Peter; Puchavskaya, Zhanna

    2016-12-01

    Vitamine D (VD) has important functions in the human brain and may play a role in affective-related disorders. VD receptors are expressed in multiple brain regions associated with depressive disorders. The aim of the preclinical study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0mg/kg/day,s.c., once daily, for 14days) on the depression-like behavior and corticosterone levels in the blood samples following ovariectomy in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5μg/rat,s.c., once daily, for 14days). Depression-like behavior and spontaneous locomotor activity were assessed in the forced swimming test (FST) and the open field test (OFT), respectively. The corticosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with cholecalciferol in high dose (5.0mg/kg/day,s.c.) significantly decreased the immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E2 exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose (5.0mg/kg/day,s.c.) administered alone or together with 17β-E2 significantly enhanced frequency of grooming for the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E2 significantly decreased the elevated corticosterone levels in the blood serum of OVX rats following the FST. These results indicate that Cholecalciferol in high dose has a marked antidepressant-like effect in the adult female rats with low levels of estrogen.

  10. Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning.

    PubMed

    Nobre, Jessica Lopes; Lisboa, Patricia Cristina; Lima, Natália da Silva; Franco, Juliana Gastão; Nogueira Neto, José Firmino; de Moura, Egberto Gaspar; de Oliveira, Elaine

    2012-04-01

    It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0·05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25-hydroxyvitamin D₃ (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition.

  11. Nicotine produces long-term increases in cocaine reinforcement in adolescent but not adult rats.

    PubMed

    Reed, Stephanie Collins; Izenwasser, Sari

    2017-01-01

    Studies have shown that many smokers begin using nicotine during adolescence, yet the influence of early nicotine use on the response to other drugs of abuse in adulthood is not fully understood. In the current study, nicotine was administered to adolescent and adult rats for seven days. Thirty days later, cocaine-induced locomotor activity and cocaine self-administration were examined when the rats pretreated as adolescents were adults. Rats exposed to nicotine during early adolescence were sensitized thirty days later to the locomotor-activating effects of cocaine and self-administered a greater number of cocaine infusions than adolescent rats pretreated with vehicle. As a result of this increased intake, the cocaine self-administration dose-response curve was shifted upward indicating an increase in cocaine reinforcement. Rats pretreated with nicotine as adults, however, did not show a difference in locomotor activity or cocaine self-administration thirty days later compared to adult rats pretreated with vehicle. These findings suggest that early exposure to nicotine has long-term consequences on cocaine use. These data further suggest that nicotine use may carry a greater risk during adolescence than adulthood and adolescents who smoke may be particularly vulnerable to stimulant use. This article is part of a Special Issue entitled SI: Adolescent plasticity.

  12. Induction of maternal behavior in adult female rats following chronic morphine exposure during puberty.

    PubMed

    Byrnes, Elizabeth M; Rigero, Beth A; Bridges, Robert S

    2003-12-01

    The peripubertal period in the female rat is the time when the stimulatory effects of opioids on prolactin (PRL) secretion develop. In the adult rat, the administration of chronic high-dose morphine has been shown to attenuate the ability of opiates to stimulate PRL secretion. One function of PRL in adult virgin rats is the induction of maternal behavior. The present study examined whether chronic high-dose morphine exposure during the peripubertal period alters PRL-mediated induction of maternal behavior in adult female rats. Two groups of juvenile female rats were administered increasing doses of morphine or vehicle (s.c.) from age 30 to 50 days. As adults, these females either remained intact, or were ovariectomized and treated with a PRL-dependent, steroid hormone regimen that stimulates a rapid onset of maternal behavior. All females were then exposed daily to rat foster pups to determine whether peripubertal morphine exposure affected their latencies to induce maternal behavior. Morphine treatment resulted in a delay in vaginal opening and a temporary reduction in the rate of weight gain; however, the rate of onset of maternal behavior was unaffected by peripubertal morphine treatment. Thus, chronic morphine exposure in the pubertal female did not impact the expression of pup-induced maternal care.

  13. Acute and adaptive motor responses to caffeine in adolescent and adult rats.

    PubMed

    Rhoads, Dennis E; Huggler, April L; Rhoads, Lucas J

    2011-07-01

    Caffeine is a psychostimulant with intake through foods or beverages tending to increase from childhood through adolescence. The goals of the present study were to examine the effects of caffeine on young adolescent Long-Evans rats and to compare the motor-behavioral responses of adolescent and adult rats to acute and chronic caffeine. Adolescent rats had a biphasic dose-response to caffeine comparable to that reported for adult rats. The magnitude of the motor response to a challenge dose of caffeine (30mg/kg, ip) was similar between adolescent and adult rats. Administration of caffeine in the drinking water (1mg/ml) for a period of 2 weeks led to overall consumption of caffeine which was not significantly different between adolescents and adults when normalized to body mass. There were no impacts of caffeinated drinking water on volume of fluid consumed nor weight gain in either age group compared to age matched controls drinking non-caffeinated tap water. Following this period of caffeine consumption, return to regular drinking water (caffeine withdrawal) led to a significant decrease in baseline movement compared to caffeine-naïve rats. This effect inversion was observed for adolescents but not adults. In addition, the response of the adolescents to the challenge dose of caffeine (30mg/kg, ip) was reduced significantly after chronic caffeine consumption and withdrawal. This apparent tolerance to the caffeine challenge dose was not seen with the adults. Thus, the developing brain of these adolescents may show similar sensitivity to adults in acute caffeine exposure but greater responsiveness to adaptive changes associated with chronic caffeine consumption.

  14. Effects of Neonatal Overfeeding on Juvenile and Adult Feeding and Energy Expenditure in the Rat

    PubMed Central

    Stefanidis, Aneta; Spencer, Sarah J.

    2012-01-01

    Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanim(s) underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL) compared with those from control litters (CL). There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active) phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males) had reduced brown adipose tissue (BAT) temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages. PMID:23251693

  15. Characterization of dsRed2-positive cells in the doublecortin-dsRed2 transgenic adult rat retina.

    PubMed

    Trost, A; Schroedl, F; Marschallinger, J; Rivera, F J; Bogner, B; Runge, C; Couillard-Despres, S; Aigner, L; Reitsamer, H A

    2014-12-01

    Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and young immature neurons of the developing and adult brain, where it is involved in neuronal differentiation, migration and plasticity. Moreover, its expression pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models have been previously used to investigate adult neurogenesis. In this study, we characterize dsRed2 reporter protein-expressing cells in the adult retina of the transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with putative neurogenic activity. Additionally, we confirmed the expression of the dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus. Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA-NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning microscopy. In addition, brain sections of transgenic rats were analyzed for dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex and dentate gyrus. Endogenous DCX expression in the adult retina was confined to horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2 reporter protein. In addition, we encountered dsRed2 expression in various other cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of amacrine cells, a minority of bipolar cells and in perivascular cells. Since also RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to study RGCs in vivo under various conditions. Müller glial cells, which have previously been identified as cells with stem cell features and with neurogenic potential, did express neither endogenous DCX nor the dsRed2 reporter. However, and surprisingly, we identified a perivascular glial cell type expressing the dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing with the

  16. Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model

    SciTech Connect

    Yang, Xiaoxia Doerge, Daniel R.; Fisher, Jeffrey W.

    2013-07-01

    Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies on the maturation of phase II enzymes coupled with serum time course data in pups. The calibrated model predicted the measured serum concentrations of BPA and BPA conjugates after administration of 100 μg/kg of d6-BPA in adult rats (oral gavage and intravenous administration) and postnatal days 3, 10, and 21 pups (oral gavage). The observed age-dependent BPA serum concentrations were partially attributed to the immature metabolic capacity of pups. A comparison of the dosimetry of BPA across immature rats and monkeys suggests that dose adjustments would be necessary to extrapolate toxicity studies from neonatal rats to infant humans. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in young and adult rats. • BPA metabolism within enterocytes is required for fitting of oral BPA kinetic data. • BPA dosimetry in young rats is different than adult rats and young monkeys.

  17. Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats.

    PubMed

    Alaa-Eldin, Eman Ahmad; El-Shafei, Dalia Abdallah; Abouhashem, Nehal S

    2017-01-01

    Commercial mixtures of chlorpyrifos and cypermethrin pesticides are widely used to enhance the toxic effects of cypermethrin on target insects. So, the purpose of the current study was to evaluate the individual and combined toxic effects of chlorpyrifos (CPF) and cypermethrin (CYP) on reproductive system of adult male albino rats. Forty adult male albino rats were randomized into main four groups: group I (control group) included 16 rats, subdivided into negative and positive control; group II (eight rats) received chlorpyrifos 6.75 mg/kg b.w./orally∕daily); group III (eight rats) (received cypermethrin 12.5 mg/kg b.w./orally∕daily); and group IV (eight rats) (received chlorpyrifos and cypermethrin at the same previously mentioned doses). All treatments were given by oral gavage for 12 weeks. We found that single CPF and CYP exposures significantly have adverse effects on reproductive function of adult male albino rats manifested by reduced testicular weight, decreased sperm count, motility and viability, significantly increased percent of morphologically abnormal spermatozoa, and significant increments in sperm DNA fragmentation index (DFI) with respect to control group. Furthermore, serum follicle stimulating hormone, luteinizing hormone, and testosterone levels were decreased significantly compared to control group. This was accompanied with histopathological changes in the testis of rats such as necrosis, degeneration, decreasing number of spermatogenic cells in some seminiferous tubules, edema, congested blood vessels, and exudate in interstitial tissue of the testis. Notably, all these changes were exaggerated in rats treated concomitantly with chlorpyrifos and cypermethrin rendering the mixture more toxic than the additive effects of each compound and causing greater damage on the reproductive system of male albino rats than the individual pesticides.

  18. Derivation, characterization, and phenotypic variation of hepatic progenitor cell lines isolated from adult rats.

    PubMed

    Yin, Li; Sun, Mingzeng; Ilic, Zoran; Leffert, Hyam L; Sell, Stewart

    2002-02-01

    Liver progenitor cells (LPCs) cloned from adult rat livers following allyl alcohol injury express hematopoietic stem cell and early hepatic lineage markers when cultured on feeder layers; under these conditions, neither mature hepatocyte nor bile duct, Ito, stellate, Kupffer cell, or macrophage markers are detected. These phenotypes have remained stable without aneuploidy or morphological transformation after more than 100 population doublings. When cultured without feeder layers, the early lineage markers disappear, and mature hepatocyte markers are expressed; mature hepatocytic differentiation and cell size are also augmented by polypeptide and steroidal growth factors. In contrast to hepatocytic potential, duct-like structures and biliary epithelial markers are expressed on Matrigel. Because they were derived without carcinogens or mutagens, these bipotential LPC lines provide novel tools for models of cellular plasticity and hepatocarcinogenesis, as well as lines for use in cellular transplantation, gene therapy, and bioreactor construction.

  19. New rat models of iron sucrose-induced iron overload.

    PubMed

    Vu'o'ng Lê, Bá; Khorsi-Cauet, Hafida; Villegier, Anne-Sophie; Bach, Véronique; Gay-Quéheillard, Jérôme

    2011-07-01

    The majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients.

  20. Characterization of membrane currents in dissociated adult rat pineal cells.

    PubMed Central

    Aguayo, L G; Weight, F F

    1988-01-01

    1. Membrane currents, particularly the outward components, were studied in pineal cells acutely dissociated from adult rats using the whole-cell variant of the patch-clamp technique. 2. In current clamp, outward constant current elicited a transient graded depolarizing response. A sustained membrane rectification developed within 20 ms; this phenomenon was reduced in cells internally dialysed with 120 mM-CsCl. 3. Study of the membrane current revealed the existence of a transient and a delayed outward current. These currents were virtually eliminated when the cell was internally dialysed with CsCl. 4. The delayed outward current, isolated from a holding potential of -50 mV, activated at potentials near -20 mV, reached a steady-state current amplitude within 60 ms and had little or no decay during steps up to 400 ms in duration. This component was reduced by 80% or more with the addition of 5 mM-TEA. 5. From -100 mV, the transient outward current reached a peak within 15 ms and decayed with a single-exponential time course. The mean decay time constant was 66 +/- 10 ms (at -33 mV) and it showed little voltage sensitivity. This current, which activated at potentials positive to -60 mV and displayed half-inactivation at -76 +/- 8 mV, was reduced by 50% with the addition of 5 mM-4-AP (4-amino-pyridine). 6. In the presence of external Ca2+, the current-voltage relationship for the delayed current did not display a region of negative-slope conductance (N-shape). Increasing the intracellular ionized Ca2+ concentration by varying the Ca-EGTA buffer ratio did not alter the dependence of the current on the membrane potential. 7. Block of outward currents with internal Cs+ revealed a small (less than 90 pA) inward Ca2+ current when the external Ca2+ concentration was increased to 10 mM. From a holding potential of -50 mV, it had a threshold at -30 mV and peaked at +5 mV. Evidence for an inward Na+ current was not obtained. 8. We conclude that acutely dissociated pineal cells

  1. 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.

  2. Ethanol facilitation of short-term memory in adult rats with a disturbed circadian cycle.

    PubMed

    Mikolajczak, P; Okulicz-Kozaryn, I; Nowaczyk, M; Kaminska, E

    2001-01-01

    The aim of this study was to evaluate the effect of 3-month ethanol treatment on olfactory social memory test performance using two inter-exposure intervals [30 min: short-term recognition (STR); or 120 min: long-term recognition (LTR)] in adult rats with a disturbed circadian cycle (DCC). Ethanol treatment both in ethanol-preferring and -non-preferring groups improved the STR task compared to control rats. However, LTR procedure triggered the opposite tendency. Moreover, no differences between control rats with DCC and those with normal diurnal rhythm in STR and LTR paradigms were observed. Our results suggest that, under some conditions, alcohol facilitates short-term memory in adult rats.

  3. Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

    PubMed

    Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

    2009-12-01

    Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

  4. Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: effects of chronic pubertal cannabinoid treatment.

    PubMed

    Schneider, Miriam; Koch, Michael

    2005-05-01

    The aim of the present study was to investigate the effects of neonatal excitotoxic lesions of the medial prefrontal cortex (mPFC) on social play, social behavior unrelated to play, and self-grooming in juvenile and adult rats. We additionally examined the behavioral effects of chronic pubertal treatment with the cannabinoid agonist WIN 55,212-2 (WIN) in order to test the hypothesis that early lesions render the brain vulnerable to cannabinoid intake in later life. Neonatal mPFC lesions and pubertal WIN treatment disrupted social play, social behavior, and self-grooming in juvenile and adult rats. Additionally, we observed more social play behaviors during light cycle in WIN-treated than in vehicle-treated rats. Notably, the combination of surgery and WIN treatment disrupted social behavior in lesioned and sham-lesioned rats. The present data indicate that the mPFC is important for adequate juvenile response selection in the context of social play and might be involved in the development of adult social and nonsocial behavior. Moreover, our data add further evidence for an involvement of the cannabinoid system in anxiety and social behavior. Additive effects of neonatal surgery-induced stress or cortical lesions in combination with pubertal cannabinoid administration are also shown. The disturbances of social and nonsocial behavior in rats are comparable to symptoms of early frontal cortex damage, as well as neurodevelopmental disorders in humans, such as schizophrenia and autism. Therefore, we propose the combination of neonatal cortical lesions with chronic cannabinoid administration during puberty as an animal model for studying neuronal mechanisms of impaired social functioning in neuropsychiatric disorders.

  5. 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.

  6. Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

    PubMed Central

    Alvarez, Pedro; Green, Paul G.; Levine, Jon D.

    2013-01-01

    Background Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear. Methods Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding, NLB) for one week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines, interleukin 6 (IL-6) and tumor necrosis alpha (TNFα) in nociception, was evaluated through of behavioral and ELISA assays, surgical interventions and intrathecal antisense treatments. Results Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6-receptor subunit gp130, but not to TNFα type 1 receptor (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared to control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNFα, whereas sound stress increases IL-6 plasma levels in control but not in NLB rats. Conclusions Early-life stress induces a persistent elevation of IL-6, hyperalgesia and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and pro-inflammatory cytokines acting at muscle nociceptor level. PMID:23706525

  7. Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

    PubMed

    Mustroph, Martina L; King, Michael A; Klein, Ronald L; Ramirez, Julio J

    2012-07-15

    Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.

  8. Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats.

    PubMed

    Aréchiga-Ceballos, F; Alvarez-Salas, E; Matamoros-Trejo, G; Amaya, M I; García-Luna, C; de Gortari, P

    2014-04-01

    Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the hypothalamus-pituitary-adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

  9. Increased rat neonatal activity influences adult cytokine levels and relative muscle mass

    PubMed Central

    Buchowicz, Bryce; Yu, Tiffany; Nance, Dwight M.; Zaldivar, Frank P.; Cooper, Dan M.; Adams, Gregory R.

    2011-01-01

    Little is known about the effect of physical activity in early life on subsequent growth and regulation of inflammation. We previously reported that exposure of muscles in growing rats to IL-6 results in decreased muscle growth apparently due to a state of resistance to growth factors such IGF-I and that running exercise could ameliorate this growth defect. Herein we hypothesized that increased activity, for a brief period during neonatal life, would pattern the adult rat towards a less inflammatory phenotype. Neonatal rats were induced to move about their cage for brief periods from day 5 to day 15 postpartum. Additional groups were undisturbed controls (CON) and handled (HAND). Sub-groups of rats were sampled at 30 and 65 days of age. Relative to CON and HAND, neonatal exercise (EX) results in decreased circulating levels of TNFα, IL-6 and IL-1β in adulthood, primarily in male rats. In addition, adult male EX rats had lower body mass and increased skeletal muscle mass suggesting a leaner phenotype. The results of this study suggest that moderate increases in activity early in life can influence the adult toward a more healthy phenotype with regard to inflammatory mediators and relative muscle mass. PMID:20657345

  10. Early life permethrin insecticide treatment leads to heart damage in adult rats.

    PubMed

    Vadhana, M S Dhivya; Carloni, Manuel; Nasuti, Cinzia; Fedeli, Donatella; Gabbianelli, Rosita

    2011-09-01

    Early life environmental exposure to xenobiotics could represent a critical period for the onset of permanent alterations in the structure and function of different organs. Cardiovascular diseases can be related to various factors including environmental toxicants. The aim of the present study was to evaluate the effect of early life permethrin treatment (1/50 LD(50), from 6th to 21st day of life) on heart of adult rats. Increased DNA damage, decreased heart cell membrane fluidity, increased cholesterol content, protein and lipid oxidation were measured in heart cells from adult rats treated with permethrin during the neonatal period with respect to control rats. Moreover, the same group showed higher levels of cholesterol, IL-1β, IL-2, IFN-γ, rat-Rantes and IL-10 cytokines and decreased albumin content in plasma. Lower cholesterol levels and perturbation in the phospholipid lateral diffusion together with decreased GSH levels and increased GPx activity were measured in heart mitochondria of the treated group. Our findings support the evidence that the neonatal period has a critical role in the development of heart disease in adulthood. We hypothesize that the alterations observed in adult rats could depend on epigenetic changes that occurred during this period which influence gene expression throughout the rat's life, leading to alterations of certain parameters related to cardiac function.

  11. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    PubMed

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  12. Gonadotropin-releasing hormone receptor in spinal cord neurons of embryos and adult rats.

    PubMed

    Quintanar, J Luis; Salinas, Eva; González, Rodolfo

    2009-09-11

    Mammalian gonadotropin-releasing hormone (GnRH) and its receptor have been found in the neuroendocrine reproductive axis. However, they can be localized in other extra-pituitary tissues as well including the central nervous system. The present study reports the expression of GnRH receptor and its mRNA in spinal cord neurons of rat embryos and adult rats, using immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemistry showed that the spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor. The study of GnRH receptor mRNAs revealed that both cultured spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor mRNA. Additional in vitro experiments showed that the expression of GnRH receptor mRNA was less in the spinal cord neurons exposed to GnRH compared to unexposed ones. These results raise the possibility that GnRH may play other roles independently from its participation in reproductive function.

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  16. Early treatment with metformin induces resistance against tumor growth in adult rats.

    PubMed

    Trombini, Amanda B; Franco, Claudinéia Cs; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane As; Fabricio, Gabriel S; de Sant'Anna, Juliane R; Castro-Prado, Marialba Aa; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo Cf

    2015-01-01

    It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.

  17. Multivariate Models of Adult Pacific Salmon Returns

    PubMed Central

    Burke, Brian J.; Peterson, William T.; Beckman, Brian R.; Morgan, Cheryl; Daly, Elizabeth A.; Litz, Marisa

    2013-01-01

    Most modeling and statistical approaches encourage simplicity, yet ecological processes are often complex, as they are influenced by numerous dynamic environmental and biological factors. Pacific salmon abundance has been highly variable over the last few decades and most forecasting models have proven inadequate, primarily because of a lack of understanding of the processes affecting variability in survival. Better methods and data for predicting the abundance of returning adults are therefore required to effectively manage the species. We combined 31 distinct indicators of the marine environment collected over an 11-year period into a multivariate analysis to summarize and predict adult spring Chinook salmon returns to the Columbia River in 2012. In addition to forecasts, this tool quantifies the strength of the relationship between various ecological indicators and salmon returns, allowing interpretation of ecosystem processes. The relative importance of indicators varied, but a few trends emerged. Adult returns of spring Chinook salmon were best described using indicators of bottom-up ecological processes such as composition and abundance of zooplankton and fish prey as well as measures of individual fish, such as growth and condition. Local indicators of temperature or coastal upwelling did not contribute as much as large-scale indicators of temperature variability, matching the spatial scale over which salmon spend the majority of their ocean residence. Results suggest that effective management of Pacific salmon requires multiple types of data and that no single indicator can represent the complex early-ocean ecology of salmon. PMID:23326586

  18. [Disruption of latent inhibition in adult rats after prepubertal dopamine terminals lesions in the ventral hippocampus].

    PubMed

    Loskutova, L V; Kostiunina, N V; Red'kina, A V

    2010-05-01

    Wistar rats were submitted to bilateral ventral hippocampal injection of 6-hydroxydopamine on 32nd day after birth. Latent inhibition was measured in passive or active avoidance tasks when the rats received 20 and 100 pre-exposures of conditioned stimulus. Prepubertal and adult lesioned rats showed a deficit in the latent inhibition but not in the capacity to avoidance learning in presence of the conditioned stimulus novelty. Possible mechanism of the involvement of hippocampal dopaminergic terminals in attention inhibition to irrelevant information is considered.

  19. Maternal exposure to isobutyl-paraben impairs social recognition in adult female rats.

    PubMed

    Kawaguchi, Maiko; Morohoshi, Kaori; Imai, Hideki; Morita, Masatoshi; Kato, Nobumasa; Himi, Toshiyuki

    2010-01-01

    Isobutyl-paraben (IBP), a widely used preservative, exhibits estrogenic activity. We analyzed the effects of exposure to IBP during gestation and lactation via dam on social recognition behavior in ovariectomized offspring of Sprague-Dawley rats. Offspring were ovariectomized at 7 weeks of age, and were used in a social recognition test at 16 weeks of age. Each offspring was exposed to a novel ovariectomized rat four times and to a second novel rat in a fifth exposure. We counted the investigations by offspring of intruder rats. The IBP-exposed rats showed impaired social behavior compared with controls. These data imply that early exposure to IBP may have an effect on adult social behavior, which is reported to be an autism spectrum disorders in humans.

  20. 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

  1. Long-distance axonal regeneration in the filum terminale of adult rats is regulated by ependymal cells.

    PubMed

    Kwiecien, Jacek M; Avram, Ronen

    2008-03-01

    Studies of regeneration of transected adult central nervous system (CNS) axons are difficult due to lack of appropriate in vivo models. In adult rats, we described filum terminale (FT), a caudal slender extension of the sacral spinal cord and an integral part of the central nervous system (CNS), to use it as a model of spinal cord injury. FT is more than 3 cm long, encompasses a central canal lined with ependymal cells surrounded by a narrow band of axons interspersed with oligodendrocytes and astrocytes but not neurons. Two weeks after the crush of FT, histological, ultrastructural, and axonal tracing studies revealed long distance descending axonal regeneration uniquely in close proximity of the ependymal cells of the central canal. Ependymal cells extended basal processes to form channels encompassing axons apparently regenerating at a rate of more than 2 mm a day. Remarkable increase of axonal sprouting was observed in the sacral spinal cord of Long Evans Shaker (LES) rats with crushed FT. FT offers an excellent model to study mechanisms of axonal regeneration regulated by ependymal cells in the adult CNS.

  2. Upper airway and abdominal motor output during sneezing: is the in vivo decererate rat an adequate model?

    PubMed

    Ono, Kenichi; Shen, Tabitha Y; Chun, Hyun Hye; Solomon, Irene C

    2010-01-01

    While numerous studies have focused on identifying and characterizing the neural mechanisms mediating upper airway defense reflexes in the anesthetized or decerebrate adult cat, little is known about these behaviors in in vivo rodent models. The current study was undertaken to investigate whether the in vivo decelerate adult rat might serve as an acceptable model for studying these behaviors. To begin to address this possibility, we examined multiple respiratory motor activities in response to mechanical stimulation of the anterior nasal cavity (sufficient to elicit fictive sneezing) in in vivo decerebrate adult rats. We found that the neural activities observed during nasal stimulation were consistent with those previously reported during fictive sneezing in the adult cat model. We suggest that the in vivo decerebrate rat is an acceptable model for studying the sneezing reflex.

  3. ADOLESCENT INTERMITTENT ETHANOL EXPOSURE ENHANCES ETHANOL ACTIVATION OF THE NUCLEUS ACCUMBENS WHILE BLUNTING THE PREFRONTAL CORTEX RESPONSES IN ADULT RAT

    PubMed Central

    LIU, W.; CREWS, F. T.

    2016-01-01

    The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on–2 days off; P25–P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood. PMID:25727639

  4. Adolescent intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat.

    PubMed

    Liu, W; Crews, F T

    2015-05-07

    The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on-2 days off; P25-P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood.

  5. Characterization of Amino Acid Profile and Enzymatic Activity in Adult Rat Astrocyte Cultures.

    PubMed

    Souza, Débora Guerini; Bellaver, Bruna; Hansel, Gisele; Arús, Bernardo Assein; Bellaver, Gabriela; Longoni, Aline; Kolling, Janaina; Wyse, Angela T S; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-07-01

    Astrocytes are multitasking players in brain complexity, possessing several receptors and mechanisms to detect, participate and modulate neuronal communication. The functionality of astrocytes has been mainly unraveled through the study of primary astrocyte cultures, and recently our research group characterized a model of astrocyte cultures derived from adult Wistar rats. We, herein, aim to characterize other basal functions of these cells to explore the potential of this model for studying the adult brain. To characterize the astrocytic phenotype, we determined the presence of GFAP, GLAST and GLT 1 proteins in cells by immunofluorescence. Next, we determined the concentrations of thirteen amino acids, ATP, ADP, adenosine and calcium in astrocyte cultures, as well as the activities of Na(+)/K(+)-ATPase and acetylcholine esterase. Furthermore, we assessed the presence of the GABA transporter 1 (GAT 1) and cannabinoid receptor 1 (CB 1) in the astrocytes. Cells demonstrated the presence of glutamine, consistent with their role in the glutamate-glutamine cycle, as well as glutamate and D-serine, amino acids classically known to act as gliotransmitters. ATP was produced and released by the cells and ADP was consumed. Calcium levels were in agreement with those reported in the literature, as were the enzymatic activities measured. The presence of GAT 1 was detected, but the presence of CB 1 was not, suggesting a decreased neuroprotective capacity in adult astrocytes under in vitro conditions. Taken together, our results show cellular functionality regarding the astrocytic role in gliotransmission and neurotransmitter management since they are able to produce and release gliotransmitters and to modulate the cholinergic and GABAergic systems.

  6. Aging Contributes to Inflammation in Upper Extremity Tendons and Declines in Forelimb Agility in a Rat Model of Upper Extremity Overuse

    PubMed Central

    Kietrys, David M.; Barr-Gillespie, Ann E.; Amin, Mamta; Wade, Christine K.; Popoff, Steve N.; Barbe, Mary F.

    2012-01-01

    We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF) handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC) as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF)-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success. PMID:23056540

  7. 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.

  8. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system.

  9. The impact of postnatal environment on opioid peptides in young and adult male Wistar rats.

    PubMed

    Gustafsson, Lisa; Oreland, Sadia; Hoffmann, Pernilla; Nylander, Ingrid

    2008-04-01

    Early environmental influences can change the neuronal development and thereby affect behavior in adult life. The aim in the present study was to thoroughly examine the impact of early environmental factors on endogenous opioids by using a rodent maternal separation (MS) model. The endogenous opioid peptide system is not fully developed at birth, and short- and/or long-term alterations may occur in these neural networks in animals exposed to manipulation of the postnatal environment. Rat pups were subjected to one of five rearing conditions; 15 min (MS15) litter (l) or individual (i), 360 min (MS360) l or i daily MS, or housed under normal animal facility rearing (AFR) conditions during postnatal days 1-21. Measurements of immunoreactive (ir) Met-enkephalin-Arg6Phe7 (MEAP) and dynorphin B (DYNB) peptide levels in the pituitary gland and in a number of brain areas, were performed at three and 10 weeks of age, respectively. MS-induced changes were more pronounced in ir MEAP levels, especially in individually separated rats at three weeks of age and in litter-separated rats at 10 weeks of age. The enkephalin and dynorphin systems have different developmental patterns, dynorphin appearing earlier, which may point at a more sensitive enkephalin system during the early postnatal weeks. The results provide evidence that opioid peptides are sensitive for early environmental factors and show that the separation conditions are critical and also result in changes manifesting at different time points. MS-induced effects were observed in areas related to stress, drug reward and dependence mechanisms. By describing effects on opioid peptides, the study addresses the possible role of a deranged endogenous opioid system in the previously described behavioral consequences of MS.

  10. A rat model for hepatitis E virus

    PubMed Central

    Mishra, Niraj; Verbeken, Erik; Ramaekers, Kaat; Dallmeier, Kai

    2016-01-01

    ABSTRACT Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies. PMID:27483350

  11. Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.

    PubMed

    Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

    2016-02-01

    Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems.

  12. Ventilatory phenotypes among four strains of adult rats.

    PubMed

    Hodges, Matthew R; Forster, Hubert V; Papanek, Paula E; Dwinell, Melinda R; Hogan, Genevieve E

    2002-09-01

    Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive (n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O(2)-88% N(2)), hypercapnia (7% CO(2)), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO(2) (P < 0.001), an accentuated ventilatory response to exercise (P < 0.05), and an accentuated ventilatory roll-off during hypoxia (P < 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains (P > 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO(2) sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO(2) sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms.

  13. Circadian rhythm of intraocular pressure in the adult rat.

    PubMed

    Lozano, Diana C; Hartwick, Andrew T E; Twa, Michael D

    2015-05-01

    Ocular hypertension is a risk factor for developing glaucoma, which consists of a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells and subsequent irreversible vision loss. Our understanding of how intraocular pressure damages the optic nerve is based on clinical measures of intraocular pressure that only gives a partial view of the dynamic pressure load inside the eye. Intraocular pressure varies over the course of the day and the oscillator regulating these daily changes has not yet been conclusively identified. The purpose of this study was to compare and contrast the circadian rhythms of intraocular pressure and body temperature in Brown Norway rats when these animals are housed in standard light-dark and continuous dim light (40-90 lux) conditions. The results from this study show that the temperature rhythm measured in continuous dim light drifted forward relative to external time, indicating that the rhythm was free running and being regulated by an internal biological clock. Also, the results show that there is a persistent, but dampened, circadian rhythm of intraocular pressure in continuous dim light and that the circadian rhythms of temperature and intraocular pressure are not synchronized by the same central oscillator. We conclude that once- or twice-daily clinical measures of intraocular pressure are insufficient to describe intraocular pressure dynamics. Similarly, our results indicate that, in experimental animal models of glaucoma, the common practice of housing animals in constant light does not necessarily eliminate the potential influence of intraocular pressure rhythms on the progression of nerve damage. Future studies should aim to determine whether an oscillator within the eye regulates the rhythm of intraocular pressure and to better characterize the impact of glaucoma on this rhythm.

  14. Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats.

    PubMed

    Glenn, Melissa J; Adams, Raven S; McClurg, Lauren

    2012-03-14

    Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10-22, on postnatal days (PD) 25-50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats' anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression.

  15. 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

  16. Postnatal ethanol exposure disrupts signal detection in adult rats.

    PubMed

    Woolfrey, Kevin M; Hunt, Pamela S; Burk, Joshua A

    2005-01-01

    Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the "brain growth spurt" has been associated with significant impairments in attention, learning, and memory. The present experiment assessed whether administration of ethanol during the brain growth spurt in the rat, which occurs shortly after birth, disrupts attentional performance. Rats were administered 5.25 g/kg/day ethanol via intragastric intubation from postnatal days (PD) 4-9, sham-intubation, or no intubation (naïve). Beginning at PD 90, animals were trained to asymptotic performance in a two-lever attention task that required discrimination of brief visual signals from trials with no signal presentation. Finally, manipulations of background noise and inter-trial interval duration were conducted. Early postnatal ethanol administration did not differentially affect acquisition of the attention task. However, after rats were trained to asymptotic performance levels, those previously exposed to ethanol demonstrated a deficit in detection of signals but not of non-signals compared to sham-intubated and naïve rats. The signal detection deficit persisted whenever these animals were re-trained in the standard task, but further task manipulations failed to interact with ethanol pretreatment. The present data support the hypothesis that early postnatal ethanol administration disrupts aspects of attentional processing in the rat.

  17. The Helsinki Rat Microsurgical Sidewall Aneurysm Model

    PubMed Central

    Marbacher, Serge; Marjamaa, Johan; Abdelhameed, Essam; Hernesniemi, Juha; Niemelä, Mika; Frösen, Juhana

    2014-01-01

    Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms. Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions. The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta. We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat. PMID:25350840

  18. Cerebral microbleeds in a neonatal rat model

    PubMed Central

    Carusillo Theriault, Brianna; Woo, Seung Kyoon; Karimy, Jason K.; Keledjian, Kaspar; Stokum, Jesse A.; Sarkar, Amrita; Coksaygan, Turhan; Ivanova, Svetlana; Gerzanich, Volodymyr

    2017-01-01

    Background In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes) dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter. Methods Pregnant Wistar rats were subjected to intrauterine ischemia (IUI) and low-dose maternal lipopolysaccharide (mLPS) at embryonic day (E) 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks. Results mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2) and protein (CD31, MMP2, MMP9) for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls. Conclusions In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development. PMID:28158198

  19. 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

  20. 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

  1. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

    PubMed

    Holtz, Nathan A; Carroll, Marilyn E

    2015-06-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

  2. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats

    PubMed Central

    Holtz, Nathan A.; Carroll, Marilyn E.

    2016-01-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability. PMID:25769092

  3. 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…

  4. 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...

  5. 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...

  6. 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...

  7. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    PubMed

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  8. Retention modeling of diesel exhaust particles in rats and humans.

    PubMed

    Yu, C P; Yoon, K J

    1991-05-01

    controlled by macrophage migration to the mucociliary escalator, whereas at high lung burdens, the clearance rate was determined principally by transport to the lymphatic system. The retention model of diesel exhaust particles for rats was extrapolated to humans of different age groups, from birth to adulthood. To derive the transport rates for the human model, the mechanical clearance from the alveolar region of the lung was assumed to be dependent on the specific particulate burden on the alveolar surface. The reduction in the mechanical clearance in adult humans caused by exposure to high concentrations of diesel exhaust was found to be much less than that observed in rats. The reduction in children was greater than that in adults.(ABSTRACT TRUNCATED AT 400 WORDS)

  9. Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

    PubMed

    Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

    2015-02-01

    Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

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

    PubMed

    Oosthuizen, M K; Amrein, I

    2016-06-02

    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.

  11. Electrophysiological properties of newborn and adult rat spinal cord glycine receptors expressed in Xenopus oocytes.

    PubMed Central

    Morales, A; Nguyen, Q T; Miledi, R

    1994-01-01

    The properties of glycine receptors (GlyRs) from newborn and adult rat spinal cord were studied in Xenopus oocytes injected with whole mRNA or the heavy (H) or light (L) mRNA fractions encoding their respective GlyRs. Mean open times and conductances of channels gated by H- or L-GlyRs were determined by noise analysis or voltage jumps. We found that adult H- and L-GlyRs opened channels that differed in their mean open time but had the same channel conductance. Both H- and L-GlyRs gated Cl- currents that displayed a similarly strong outward rectification. Nevertheless, single channels of adult H- and L-GlyRs did not rectify and their mean open times were only slightly altered by voltage. It follows that the outward rectification of adult GlyRs is due mainly to a reduction in the number of open channels. In contrast to H-GlyRs, whose characteristics seem to remain essentially unchanged with age, L-GlyRs from newborn and adult rats have different properties. Channels of newborn L-GlyRs have a higher conductance, longer open time, and greater voltage dependency than those from the adult. Interestingly, properties of newborn GlyRs expressed by whole mRNA were markedly different from those encoded by newborn or adult L or H mRNA. These results demonstrate that the functional heterogeneity of GlyRs is developmentally regulated. PMID:8159710

  12. The effect of treadmill training on motor recovery after a partial spinal cord compression-injury in the adult rat.

    PubMed

    Multon, Sylvie; Franzen, Rachelle; Poirrier, Anne-Lise; Scholtes, Felix; Schoenen, Jean

    2003-08-01

    Locomotor training on a treadmill is a therapeutic strategy used for several years in human paraplegics in whom it was shown to improve functional recovery mainly after incomplete spinal cord lesions. The precise mechanisms underlying its effects are not known. Experimental studies in adult animals were chiefly performed after complete spinal transections. The objective of this experiment was to assess the effects of early treadmill training on recovery of spontaneous walking capacity after a partial spinal cord lesion in adult rats. Following a compression-injury by a subdurally inflated microballoon, seven rats were trained daily on a treadmill with a body weight support system, whereas six other animals were used as controls and only handled. Spontaneous walking ability in an open field was compared weekly between both groups by two blinded observers, using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Mean BBB score during 12 weeks was globally significantly greater in the treadmill-trained animals than in the control group, the benefit of training appearing as early as the 2nd week. At week 7, locomotor recovery reached a plateau in both animal groups, but remained superior in trained rats. Daily treadmill training started early after a partial spinal cord lesion in adult rats, which accelerates recovery of locomotion and produces a long-term benefit. These findings in an animal model mimicking the closed spinal cord injury occurring in most human paraplegics are useful for future studies of optimal locomotor training programs, their neurobiologic mechanisms, and their combination with other treatment strategies.

  13. Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

    PubMed Central

    Chan, Jackie K. W.; Fanucchi, Michelle V.; Anderson, Donald S.; Abid, Aamir D.; Wallis, Christopher D.; Dickinson, Dale A.; Kumfer, Benjamin M.; Kennedy, Ian M.; Wexler, Anthony S.; Van Winkle, Laura S.

    2011-01-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth. PMID:21914721

  14. Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs.

    PubMed

    Chan, Jackie K W; Fanucchi, Michelle V; Anderson, Donald S; Abid, Aamir D; Wallis, Christopher D; Dickinson, Dale A; Kumfer, Benjamin M; Kennedy, Ian M; Wexler, Anthony S; Van Winkle, Laura S

    2011-12-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth.

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

    PubMed

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

    2008-12-01

    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 radio-telemetric 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.

  16. Digital replantation teaching model in rats.

    PubMed

    Ad-El, D D; Harper, A; Hoffman, L A

    2000-01-01

    Replant surgery is a complex procedure that requires advanced microsurgical skills and is usually performed as an emergency operation, lasting many hours. For these reasons, teaching replantation is difficult. Although teaching models exist, they are often too general or complicated for routine use and do not simulate the stages and the pitfalls of human replant surgery. We have designed a model that is simple and imitates human replant surgery. After reviewing the rat anatomy, students dissect and replant a rat hind limb that has been sharply amputated by the instructor. They follow the same principles of "real" surgery like debridement, minimizing ischemia time, and stable fixation before anatomosis of vessels. After marking the structures, bony fixation followed by vessel and nerve anastomosis are performed. Muscle is reattached to the skin and limb vascularity evaluated. After we designed this model, plastic surgery residents performed the technique on 10 rats. An 80% limb viability rate was achieved. This model is simple to perform, simulates all the relevant structures and pitfalls of human surgery, and the rats are relatively cheap and can be used for other parallel projects.

  17. Evaluation of deltamethrin kinetics and dosimetry in the maturing rat using a PBPK model

    SciTech Connect

    Tornero-Velez, Rogelio; Mirfazaelian, Ahmad; Kim, Kyu-Bong; Anand, Sathanandam S.; Kim, Hyo J.; Haines, Wendy T.; Bruckner, James V.; Fisher, Jeffrey W.

    2010-04-15

    Immature rats are more susceptible than adults to the acute neurotoxicity of pyrethroid insecticides like deltamethrin (DLM). A companion kinetics study (Kim et al., in press) revealed that blood and brain levels of the neuroactive parent compound were inversely related to age in rats 10, 21, 40 and 90 days old. The objective of the current study was to modify a physiologically based pharmacokinetic (PBPK) model of DLM disposition in the adult male Sprague-Dawley rat (Mirfazaelian et al., 2006), so blood and target organ dosimetry could be accurately predicted during maturation. Age-specific organ weights and age-dependent changes in the oxidative and hydrolytic clearance of DLM were modeled with a generalized Michaelis-Menten model for growth and the summary equations incorporated into the PBPK model. The model's simulations compared favorably with empirical DLM time-courses in plasma, blood, brain and fat for the four age-groups evaluated (10, 21, 40 and 90 days old). PND 10 pups' area under the 24-h brain concentration time curve (AUC{sub 0-24h}) was 3.8-fold higher than that of the PND 90 adults. Our maturing rat PBPK model allows for updating with age- and chemical-dependent parameters, so pyrethroid dosimetry can be forecast in young and aged individuals. Hence, this model provides a methodology for risk assessors to consider age-specific adjustments to oral Reference Doses on the basis of PK differences.

  18. 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…

  19. Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats

    PubMed Central

    Glenn, Melissa J.; Adams, Raven S.; McClurg, Lauren

    2012-01-01

    Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10–22, on postnatal days (PD) 25–50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats’ anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. PMID:22305146

  20. Early life versus lifelong oral manganese exposure differently impairs skilled forelimb performance in adult rats

    PubMed Central

    Beaudin, Stephane A.; Nisam, Sean; Smith, Donald R.

    2013-01-01

    Recent studies of children suggest that exposure to elevated manganese (Mn) levels disrupt aspects of motor, cognitive and behavioral functions that are dependent on dopamine brain systems. Although basal ganglia motor functions are well-known targets of adult occupational Mn exposure, the extent of motor function deficits in adults as a result of early life Mn exposure is unknown. Here we used a rodent model early life versus lifelong oral Mn exposure and the Montoya staircase test to determine whether developmental Mn exposure produces long-lasting deficits in sensorimotor performance in adulthood. Long-Evans male neonate rats (n=11/treatment) were exposed daily to oral Mn at levels of 0, 25, or 50 mg Mn/kg/d from postnatal day (PND) 1-21 (early life only), or from PND 1 - throughout life. Staircase testing began at age PND 120 and lasted 1 month to objectively quantify measures of skilled forelimb use in reaching and pellet grasping/retrieval performance. Behavioral reactivity also was rated on each trial. Results revealed that (1) behavioral reactivity scores were significantly greater in the Mn-exposed groups, compared to controls, during the staircase acclimation/training stage, but not the latter testing stages, (2) early life Mn exposure alone caused long-lasting impairments in fine motor control of reaching skills at the higher, but not lower Mn dose, (3) lifelong Mn exposure from drinking water led to widespread impairment in reaching and grasping/retrieval performance in adult rats, with the lower Mn dose group showing the greatest impairment, and (4) lifelong Mn exposure produced similar (higher Mn group) or more severe (lower Mn group) impairments compared to their early life-only Mn exposed counterparts. Collectively, these results substantiate the emerging clinical evidence in children showing associations between environmental Mn exposure and deficits in fine sensorimotor function. They also show that the objective quantification of skilled motor

  1. Diagnostic accuracy of evoked potentials for functional impairment after contusive spinal cord injury in adult rats.

    PubMed

    Thirumala, Parthasarathy; Zhou, James; Krishnan, Rohan; Manem, Nihita; Umredkar, Shreya; Hamilton, D K; Balzer, Jeffrey R; Oudega, Martin

    2016-03-01

    Iatrogenic spinal cord injury (SCI) is a cause of potentially debilitating post-operative neurologic complications. Currently, intra-operative neurophysiological monitoring (IONM) via somatosensory evoked potentials and motor-evoked potentials is used to detect and prevent impending SCI. However, no empirically validated interventions exist to halt the progression of iatrogenic SCI once it is detected. This is in part due to the lack of a suitable translational model that mimics the circumstances surrounding iatrogenic SCI detected via IONM. Here, we evaluate a model of simulated contusive iatrogenic SCI detected via IONM in adult female Sprague-Dawley rats. We show that transient losses of somatosensory evoked potentials responses are 88.24% sensitive (95% confidence interval [CI] 63.53-98.20) and 80% specific (95% CI 51.91-95.43) for significant functional impairment following simulated iatrogenic SCI. Similarly, we show that transient losses in motor-evoked potentials responses are 70.83% sensitive (95% CI 48.91-87.33) and 100% specific (95% CI 62.91-100.00) for significant functional impairment following simulated iatrogenic SCI. These results indicate that our model is a suitable replica of the circumstances surrounding clinical iatrogenic SCI.

  2. Adolescent and adult male rats habituate to repeated isolation, but only adolescents sensitize to partner unfamiliarity.

    PubMed

    Hodges, Travis E; McCormick, Cheryl M

    2015-03-01

    We investigated whether adolescent male rats show less habituation of corticosterone release than adult male rats to acute vs repeated (16) daily one hour episodes of isolation stress, as well as the role of partner familiarity during recovery on social behavior, plasma corticosterone, and Zif268 expression in brain regions. Adolescents spent more time in social contact than did adults during the initial days of the repeated stress procedures, but both adolescents and adults that returned to an unfamiliar peer after isolation had higher social activity than rats returned to a familiar peer (p=0.002) or undisturbed control rats (p<0.001). Both ages showed evidence of habituation, with reduced corticosterone response to repeated than acute isolation (p=0.01). Adolescents, however, showed sensitized corticosterone release to repeated compared with an acute pairing with an unfamiliar peer during recovery (p=0.03), a difference not found in adults. Consistent with habituation of corticosterone release, the repeated isolation groups had lower Zif268 immunoreactive cell counts in the paraventricular nucleus (p<0.001) and in the arcuate nucleus (p=0.002) than did the acute groups, and adolescents had higher Zif268 immunoreactive cell counts in the paraventricular nucleus than did adults during the recovery period (p<0.001), irrespective of stress history and partner familiarity. Partner familiarity had only modest effects on Zif268 immunoreactivity, and experimental effects on plasma testosterone concentrations were only in adults. The results highlight social and endocrine factors that may underlie the greater vulnerability of the adolescent period of development.

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

    PubMed

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

    2011-02-01

    Alcohol abuse and dependence are considered public health problems, with an etiological onset often occurring 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, intragastrically [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 adolescents and adults, respectively) using SOC. Experiment 1 revealed 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, the 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. 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 postingestive effects of high-dose ethanol as similarly aversive when assessed by SOC.

  4. 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.

  5. MODELING OPERANT BEHAVIOR IN THE PARKINSONIAN RAT

    PubMed Central

    Avila, Irene; Reilly, Mark P.; Sanabria, Federico; Posadas-Sánchez, Diana; Chavez, Claudia L.; Banerjee, Nikhil; Killeen, Peter; Castañeda, Edward

    2009-01-01

    Mathematical principles of reinforcement (MPR; Killeen, 1994) is a quantitative model of operant behavior that contains 3 parameters representing motor capacity (δ), motivation (a), and short term memory (λ). The present study applied MPR to characterize the effects of bilateral infusions of 6-OHDA into the substantia nigra pars compacta in the rat, a model of Parkinson’s disease. Rats were trained to lever press under a 5-component fixed ratio (5, 15, 30, 60, and 100) schedule of food reinforcement. Rats were tested for 15 days prior to dopamine lesions and again for 15 days post-lesion. To characterize functional loss relative to lesion size, rats were grouped according to the extent and the degree of lateralization of their dopamine loss. Response rates decreased as a function of dopamine depletion, primarily at intermediate ratios. MPR accounted for 98% of variance in pre- and post-lesion response rates. Consistent with reported disruptions in motor behavior induced by dopaminergic lesions, estimates of δ increased when dopamine was severely depleted. There was no support for different estimates of a based on pre- and post-lesion performance of any lesion group, suggesting that dopamine loss has negligible effects on incentive motivation. The present study demonstrates the usefulness of combining operant techniques with a theoretical model to better understand the effects of a neurochemical manipulation. PMID:19073222

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

    PubMed

    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.

  7. Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats

    PubMed Central

    McCall, Nora; Mahadevia, Darshini; Corriveau, Jennifer A.; Glenn, Melissa

    2016-01-01

    The present study explored the effects of supplementing male rats with either choline, omega-3 fatty acids, or phytoestrogens, from weaning into early adulthood, on emotionality and hippocampal plasticity. Because of the neuroprotective properties of these nutrients, we hypothesized that they would positively affect both behavior and hippocampal function when compared to non-supplemented control rats. To test this hypothesis, male Sprague Dawley rats were assigned to one of four nutrient conditions after weaning: 1) control (normal rat chow); 2) choline (supplemented in drinking water); 3) omega 3 fatty acids (daily oral supplements); or 4) phytoestrogens (supplemented in chow). After 4 weeks on their respective diets, a subset of rats began 3 weeks of behavioral testing, while the remaining behaviorally naïve rats were sacrificed after 6 weeks on the diets to assess numbers of adult-born hippocampal neurons using the immature neuron marker, doublecortin. The results revealed that choline supplementation affected emotional functioning; compared to rats in other diet conditions, rats in this group were less anxious in an open field and after exposure to predator odor and showed less behavioral despair after forced swimming. Similar behavioral findings were evident following supplementation with omega-3 fatty acids and phytoestrogens supplementation, though not on all tests and not to the same magnitude. Histological findings followed a pattern consistent with the behavioral findings: choline supplementation, followed by omega-3 fatty acid supplementation, but not phytoestrogen supplementation, significantly increased the numbers of new-born hippocampal neurons. Choline and omega −3 fatty acids have similar biological functions—affecting cell membranes, growth factor levels, and epigenetically altering gene transcription. Thus, the present findings suggest that targeting nutrients with these effects may be a viable strategy to combat adult psychopathologies

  8. Prenatal centrifugation: A model for fetal programming of adult weight?

    NASA Astrophysics Data System (ADS)

    Baer, Lisa A.; Rushing, Linda; Wade, Charles E.; Ronca, April E.

    2005-08-01

    'Fetal programming' is a newly emerging field that is revealing astounding insights into the prenatal origins of adult disease, including metabolic, endocrine, and cardiovascular pathophysiology. In the present study, we tested the hypothesis that rat pups conceived, gestated and born at 2-g have significantly reduced birth weights and increased adult body weights as compared to 1-g controls. Offspring were produced by mating young adult male and female rats that were adapted to 2-g centrifugation. Female rats underwent conception, pregnancy and birth at 2-g. Newborn pups in the 2-g condition were removed from the centrifuge and fostered to non-manipulated, newly parturient dams maintained at 1-g. Comparisons were made with 1-g stationary controls, also cross- fostered at birth. As compared to 1-g controls, birth weights of pups gestated and born at 2-g were significantly reduced. Pup body weights were significantly reduced until Postnatal day (P)12. Beginning on P63, body weights of 2-g-gestated offspring exceeded those of 1-g controls by 7-10%. Thus, prenatal rearing at 2-g restricts neonatal growth and increases adult body weight. Collectively, these data support the hypothesis that 2-g centrifugation alters the intrauterine milieu, thereby inducing persistent changes in adult phenotype.

  9. Optical coherence tomography reveals in vivo cortical structures of adult rats in response to cerebral ischemia injury

    NASA Astrophysics Data System (ADS)

    Ni, Yi-rong; Guo, Zhou-yi; Shu, So-yun; Bao, Xin-min

    2008-12-01

    Optical coherence tomography(OCT) is a high resolution imaging technique which uses light to directly image living tissue. we investigate the potential use of OCT for structural imaging of the ischemia injury mammalian cerebral cortex. And we examine models of middle cerebral artery occlusion (MCAO) in rats in vivo using OCT. In particular, we show that OCT can perform in vivo detection of cortex and differentiate normal and abnormal cortical anatomy. This OCT system in this study provided an axial resolution of 10~15μ m, the transverse resolution of the system is about 25 μm. OCT can provide cross-sectional images of cortical of adult rats in response to cerebral ischemia injury.We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the cerebral cortex structures and may offer a new tool for Possible neuroscience clinical applications.

  10. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  11. The role of testicular hormones and luteinizing hormone in spatial memory in adult male rats.

    PubMed

    McConnell, Sarah E A; Alla, Juliet; Wheat, Elizabeth; Romeo, Russell D; McEwen, Bruce; Thornton, Janice E

    2012-04-01

    Attempts to determine the influence of testicular hormones on learning and memory in males have yielded contradictory results. The present studies examined whether testicular hormones are important for maximal levels of spatial memory in young adult male rats. To minimize any effect of stress, we used the Object Location Task which is a spatial working memory task that does not involve food or water deprivation or aversive stimuli for motivation. In Experiment 1 sham gonadectomized male rats demonstrated robust spatial memory, but gonadectomized males showed diminished spatial memory. In Experiment 2 subcutaneous testosterone (T) capsules restored spatial memory performance in gonadectomized male rats, while rats with blank capsules demonstrated compromised spatial memory. In Experiment 3, gonadectomized male rats implanted with blank capsules again showed compromised spatial memory, while those with T, dihydrotestosterone (DHT), or estradiol (E) capsules demonstrated robust spatial memory, indicating that T's effects may be mediated by its conversion to E or to DHT. Gonadectomized male rats injected with Antide, a gonadotropin-releasing hormone receptor antagonist which lowers luteinizing hormone levels, also demonstrated spatial memory, comparable to that shown by T-, E-, or DHT-treated males. These data indicate that testicular androgens are important for maximal levels of spatial working memory in male rats, that testosterone may be converted to E and/or DHT to exert its effects, and that some of the effects of these steroid hormones may occur via negative feedback effects on LH.

  12. Effect of morphine, naloxone and histamine system on water intake in adult male rats.

    PubMed

    Eidi, Maryam; Oryan, Shahrbanoo; Eidi, Akram; Sepehrara, Leili

    2003-10-08

    The present study investigated the interaction between histamine and opioid systems on water intake in adult male rats. Intracerebroventricular (i.c.v.) injections were carried out in all experiments. Water intake was measured 1 h after drug injections. Administration of histamine (40-80 microg/rat) and naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat), pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased water intake in isolated rats. Blockade of histamine H1 and H2 receptors attenuated the histamine-induced response. Pyrilamine, but not ranitidine, increased the inhibitory effect induced by morphine. Also, pharmacological blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect on water intake. It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior.

  13. Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats.

    PubMed

    Chin, Vivien S; Van Skike, Candice E; Berry, Raymond B; Kirk, Roger E; Diaz-Granados, Jamie; Matthews, Douglas B

    2011-08-01

    The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA(A) receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.

  14. Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage.

    PubMed

    Delcour, Maxime; Russier, Michaël; Amin, Mamta; Baud, Olivier; Paban, Véronique; Barbe, Mary F; Coq, Jacques-Olivier

    2012-06-15

    Early brain damage, such as white matter damage (WMD), resulting from perinatal hypoxia-ischemia in preterm and low birth weight infants represents a high risk factor for mortality and chronic disabilities, including sensory, motor, behavioral and cognitive disorders. In previous studies, we developed a model of WMD based on prenatal ischemia (PI), induced by unilateral ligation of uterine artery at E17 in pregnant rats. We have shown that PI reproduced some of the main deficits observed in preterm infants, such as white and gray matter damage, myelination deficits, locomotor, sensorimotor, and short-term memory impairments, as well as related musculoskeletal and neuroanatomical histopathologies [1-3]. Here, we determined the deleterious impact of PI on several behavioral and cognitive abilities in adult rats, as well as on the neuroanatomical substratum in various related brain areas. Adult PI rats exhibited spontaneous exploratory and motor hyperactivity, deficits in information encoding, and deficits in short- and long-term object memory tasks, but no impairments in spatial learning or working memory in watermaze tasks. These results were in accordance with white matter injury and damage in the medial and lateral entorhinal cortices, as detected by axonal degeneration, astrogliosis and neuronal density. Although there was astrogliosis and axonal degeneration in the fornix, hippocampus and cingulate cortex, neuronal density in the hippocampus and cingulate cortex was not affected by PI. Levels of spontaneous hyperactivity, deficits in object memory tasks, neuronal density in the medial and lateral entorhinal cortices, and astrogliosis in the fornix correlated with birth weight in PI rats. Thus, this rodent model of WMD based on PI appears to recapitulate the main neurobehavioral and neuroanatomical human deficits often observed in preterm children with a perinatal history of ischemia.

  15. Early social isolation disrupts latent inhibition and increases dopamine D2 receptor expression in the medial prefrontal cortex and nucleus accumbens of adult rats.

    PubMed

    Han, Xiao; Li, Nanxin; Xue, Xiaofang; Shao, Feng; Wang, Weiwen

    2012-04-04

    Adolescence is a critical period for neurodevelopment. In the present study, we investigated the effects of peri-adolescent social isolation on latent inhibition (LI) and dopamine D2 receptor expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) of young adult rats. Male Sprague-Dawley rats were randomly divided into adolescent isolation (ISO; isolated housing, 21-34 days of age) and social housing (SOC) groups. LI was tested at postnatal day 56. After behavioral testing, the number of dopamine D2 receptor-expressing cells was determined using immunohistochemistry. Adolescent social isolation impaired LI and increased the number of cells expressing the D2 receptor in the mPFC and NAc. The results suggest that adolescent social isolation produces profound effects on cognitive and dopaminergic function in adult rats, and could be used as an animal model of various neurodevelopmental disorders.

  16. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  17. Molecular and immunocytochemical characterization of primary neuronal cultures from adult rat brain: Differential expression of neuronal and glial protein markers.

    PubMed

    Ray, Balmiki; Bailey, Jason A; Sarkar, Sumit; Lahiri, Debomoy K

    2009-11-15

    Neurobiological studies using primary neuronal cultures commonly employ fetal-derived neurons, but much less often adult brain-derived neurons. Our goal is to perform morphological and molecular characterization of primary neuronal cultures from adult rat brain, including the relative expression of neuronal and glial cell markers at different time points. We tested the hypothesis that long-term neuronal viability is compatible with glial proliferation in adult neuron culture. We examined neuron culture from adult rat brain, which was maintained at steady state up to 24 days, and characterized them on the basis of cellular, molecular and biochemical properties at different time points of the culture. We identified neuronal and glial cells by both immunocytochemical and western immunoblotting techniques using NSE and Tau as neuronal markers and GFAP as glial protein marker, which revealed the presence of predominantly neuronal cells in the initial phase of the culture and a rise in glial cells from day 12 onwards. Notably, neuronal cells were preserved in the culture along with the glial cells even at day 24. Transfection of the cultured cells with a GFP expression vector and plasmids containing a luciferase reporter gene under the control of two different gene promoters demonstrated DNA transfectability. Taken together, these results suggest a differential expression of neuronal and glial cells at different time points and long-term neuronal viability in the presence of glial proliferation. Such adult neurons serve as a suitable system for the application of neurodegeneration models and for drug target discovery in various brain disorders including Alzheimer's disease.

  18. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    SciTech Connect

    Tonk, Elisa C.M.; Verhoef, Aart; Gremmer, Eric R.; Loveren, Henk van; Piersma, Aldert H.

    2012-04-01

    The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the

  19. Beer promotes high levels of alcohol intake in adolescent and adult alcohol-preferring rats.

    PubMed

    Hargreaves, Garth A; Wang, Emyo Y J; Lawrence, Andrew J; McGregor, Iain S

    2011-08-01

    Previous studies suggest that high levels of alcohol consumption can be obtained in laboratory rats by using beer as a test solution. The present study extended these observations to examine the intake of beer and equivalent dilute ethanol solutions with an inbred line of alcohol-preferring P rats. In Experiment 1, male adolescent P rats and age-matched Wistar rats had access to either beer or equivalent ethanol solutions for 1h daily in a custom-built lickometer apparatus. In subsequent experiments, adolescent (Experiment 2) and adult (Experiment 3) male P rats were given continuous 24-h home cage access to beer or dilute ethanol solutions, with concomitant access to lab chow and water. In each experiment, the alcohol content of the beer and dilute ethanol solutions was gradually increased from 0.4, 1.4, 2.4, 3.4, 4.4, 5 to 10% EtOH (vol/vol). All three experiments showed a major augmentation of alcohol intake when rats were given beer compared with equivalent ethanol solutions. In Experiment 1, the overall intake of beer was higher in P rats compared with Wistar rats, but no strain difference was found during the 1-h sessions with plain ethanol consumption. Experiment 1 also showed that an alcohol deprivation effect was more readily obtained in rats with a history of consuming beer rather than plain ethanol solutions. In Experiments 2 and 3, voluntary beer intake in P rats represented ethanol intake of 10-15 g/kg/day, among the highest reported in any study with rats. This excessive consumption was most apparent in adolescent rats. Beer consumption markedly exceeded plain ethanol intake in these experiments except at the highest alcohol concentration (10%) tested. The advantage of using beer rather than dilute ethanol solutions in both selected and nonselected rat strains is therefore confirmed. Our findings encourage the use of beer with alcohol-preferring rats in future research that seeks to obtain high levels of alcohol self-administration.

  20. Competency-Based Adult Education: Florida Model.

    ERIC Educational Resources Information Center

    Singer, Elizabeth

    This compilation of program materials serves as an introduction to Florida's Brevard Community College's (BCC's) Competency-Based Adult High School Completion Project, a multi-year project designed to teach adult administrators, counselors, and teachers how to organize and implement a competency-based adult education (CBAE) program; to critique…

  1. 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.

  2. 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.

  3. A Rat Model for Muscle Regeneration in the Soft Palate

    PubMed Central

    Carvajal Monroy, Paola L.; Grefte, Sander; Kuijpers-Jagtman, Anne M.; Helmich, Maria P. A. C.; Ulrich, Dietmar J. O.; Von den Hoff, Johannes W.; Wagener, Frank A. D. T. G.

    2013-01-01

    Background Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. Despite successful surgical repositioning of the muscles, optimal function is often not achieved. Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. Therefore, the aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury. Methods Fourteen adult male Sprague Dawley rats were divided into four groups. Groups 1 (n = 4) and 2 (n = 2) were used to investigate the anatomy and histology of the soft palate, respectively. Group 3 (n = 6) was used for surgical wounding of the soft palate, and group 4 (n = 2) was used as unwounded control group. The wounds (1 mm) were evaluated by (immuno)histochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA) after 7 days. Results The present study shows that the anatomy and histology of the soft palate muscles of the rat is largely comparable with that in humans. All wounds showed clinical evidence of healing after 7 days. AZAN staining demonstrated extensive collagen deposition in the wound area, and initial regeneration of muscle fibers and salivary glands. Proliferating and differentiating satellite cells were identified in the wound area by antibody staining. Conclusions This model is the first, suitable for studying muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after cleft palate surgery. PMID:23554995

  4. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    PubMed

    MacPhail, R C; Farmer, J D; Jarema, K A

    2012-01-01

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

  5. Effect of amphetamine on adult male and female rats prenatally exposed to methamphetamine.

    PubMed

    Šlamberová, Romana; Macúchová, Eva; Nohejlová, Kateryna; Štofková, Andrea; Jurčovičová, Jana

    2014-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  6. Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats.

    PubMed

    Tash, Joseph S; Johnson, Donald C; Enders, George C

    2002-03-01

    The International Space Station will allow extended habitation in space and long-term exposure to microgravity (microG). A concern is the impact of long-term microG exposure on the ability of species to reproduce. The model often used to simulate microG is rat hindlimb suspension (HLS), where the hindlimbs are elevated above the cage floor with a tail harness. Experiments described here are the first to examine the effect of long-term HLS on testicular function in adult male rats. Free-roaming (controls), animals with only the tail harnessed but hindlimbs in contact with the cage floor (TO), and HLS animals were tested for 6 wk. Cryptorchidism was prevented in TO and HLS animals by partial constriction of the inguinal canal with sutures. All parameters were compared at the end of the 6-wk experiment. Testicular weights and spermatogenesis were significantly reduced by HLS, such that no spermatogenic cells beyond round spermatids were present and epididymides were devoid of mature sperm. In many tubules, loss of all germ cells, except a few spermatogonia, resulting in histopathology similar to the Sertoli cell, was observed. Spermatogenesis appeared unaffected in control and TO animals. Sertoli and Leydig cell appearance, testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and epididymal and seminal vesicle weight were unchanged by HLS. Cortisone was not elevated by HLS; thus stress may not be a factor. These results demonstrate that spermatogenesis is severely inhibited by long-term HLS, whereas testicular androgen production is not. These results have significant implications regarding serious effects of long-term exposure to microG on the reproductive capability of scrotal mammals, including humans.

  7. Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats

    NASA Technical Reports Server (NTRS)

    Tash, Joseph S.; Johnson, Donald C.; Enders, George C.

    2002-01-01

    The International Space Station will allow extended habitation in space and long-term exposure to microgravity (microG). A concern is the impact of long-term microG exposure on the ability of species to reproduce. The model often used to simulate microG is rat hindlimb suspension (HLS), where the hindlimbs are elevated above the cage floor with a tail harness. Experiments described here are the first to examine the effect of long-term HLS on testicular function in adult male rats. Free-roaming (controls), animals with only the tail harnessed but hindlimbs in contact with the cage floor (TO), and HLS animals were tested for 6 wk. Cryptorchidism was prevented in TO and HLS animals by partial constriction of the inguinal canal with sutures. All parameters were compared at the end of the 6-wk experiment. Testicular weights and spermatogenesis were significantly reduced by HLS, such that no spermatogenic cells beyond round spermatids were present and epididymides were devoid of mature sperm. In many tubules, loss of all germ cells, except a few spermatogonia, resulting in histopathology similar to the Sertoli cell, was observed. Spermatogenesis appeared unaffected in control and TO animals. Sertoli and Leydig cell appearance, testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and epididymal and seminal vesicle weight were unchanged by HLS. Cortisone was not elevated by HLS; thus stress may not be a factor. These results demonstrate that spermatogenesis is severely inhibited by long-term HLS, whereas testicular androgen production is not. These results have significant implications regarding serious effects of long-term exposure to microG on the reproductive capability of scrotal mammals, including humans.

  8. Fetal iron deficiency alters the proteome of adult rat hippocampal synaptosomes

    PubMed Central

    Dakoji, Srikanth; Reise, Kathryn H.; Storey, Kathleen K.; Georgieff, Michael K.

    2013-01-01

    Fetal and neonatal iron deficiency results in cognitive impairments in adulthood despite prompt postnatal iron replenishment. To systematically determine whether abnormal expression and localization of proteins that regulate adult synaptic efficacy are involved, we used a quantitative proteomic approach (isobaric tags for relative and absolute quantitation, iTRAQ) and pathway analysis to identify dysregulated proteins in hippocampal synapses of fetal iron deficiency model. Rat pups were made iron deficient (ID) from gestational day 2 through postnatal day (P) 7 by providing pregnant and nursing dams an ID diet (4 ppm Fe) after which they were rescued with an iron-sufficient diet (200 ppm Fe). This paradigm resulted in a 40% loss of brain iron at P15 with complete recovery by P56. Synaptosomes were prepared from hippocampi of the formerly iron-deficient (FID) and always iron-sufficient controls rats at P65 using a sucrose gradient method. Six replicates per group that underwent iTRAQ labeling and LC-MS/MS analysis for protein identification and comparison elucidated 331 differentially expressed proteins. Western analysis was used to confirm findings for selected proteins in the glutamate receptor signaling pathway, which regulates hippocampal synaptic plasticity, a cellular process critical for learning and memory. Bioinformatics were performed using knowledge-based Interactive Pathway Analysis. FID synaptosomes show altered expression of synaptic proteins-mediated cellular signalings, supporting persistent impacts of fetal iron deficiency on synaptic efficacy, which likely cause the cognitive dysfunction and neurobehavioral abnormalities. Importantly, the findings uncover previously unsuspected pathways, including neuronal nitric oxide synthase signaling, identifying additional mechanisms that may contribute to the long-term biobehavioral deficits. PMID:24089371

  9. Trigeminothalamic barrelette neurons: natural structural side asymmetries and sensory input-dependent plasticity in adult rats.

    PubMed

    Negredo, P; Martin, Y B; Lagares, A; Castro, J; Villacorta, J A; Avendaño, C

    2009-11-10

    In the rodent trigeminal principal nucleus (Pr5) the barrelette thalamic-projecting neurons relay information from individual whiskers to corresponding contralateral thalamic barreloids. Here we investigated the presence of lateral asymmetries in the dendritic trees of these neurons, and the morphometric changes resulting from input-dependent plasticity in young adult rats. After retrograde labeling with dextran amines from the thalamus, neurons were digitally reconstructed with Neurolucida, and metrically and topologically analyzed with NeuroExplorer. The most unexpected and remarkable result was the observation of side-to-side asymmetries in the barrelette neurons of control rats. These asymmetries more significantly involved the number of low-grade trees and the total dendritic length, which were greater on the left side. Chronic global input loss resulting from infraorbital nerve (IoN) transection, or loss of active touch resulting from whisker clipping in the right neutralized, or even reversed, the observed lateral differences. While results after IoN transection have to be interpreted in the context of partial neuron death in this model, profound bilateral changes were found after haptic loss, which is achieved without inflicting any nerve damage. After whisker trimming, neurons on the left side closely resembled neurons on the right in controls, the natural dendritic length asymmetry being reversed mainly by a shortening of the left trees and a more moderate elongation of the right trees. These results demonstrate that dendritic morphometry is both side- and input-dependent, and that unilateral manipulation of the sensory periphery leads to bilateral morphometric changes in second order neurons of the whisker-barrel system. The presence of anatomical asymmetries in neural structures involved in early stages of somatosensory processing could help explain the expression of sensory input-dependent behavioral asymmetries.

  10. Quality Assurance Model for Digital Adult Education Materials

    ERIC Educational Resources Information Center

    Dimou, Helen; Kameas, Achilles

    2016-01-01

    Purpose: This paper aims to present a model for the quality assurance of digital educational material that is appropriate for adult education. The proposed model adopts the software quality standard ISO/IEC 9126 and takes into account adult learning theories, Bloom's taxonomy of learning objectives and two instructional design models: Kolb's model…

  11. Theophylline Regulates Inflammatory and Neurotrophic factor Signals in Functional Recovery after C2-Hemisection in Adult Rats

    PubMed Central

    Singh, LP; Devi, TS; Nantwi, KD

    2012-01-01

    Recovery of respiratory activity in an upper cervical hemisection model (C2H) of spinal cord injury (SCI) can be induced by systemic theophylline administration 24–48 h after injury. The objectives in the present study are (1) to identify pro-inflammatory and neurotrophic factors expressed after C2H and (2) molecular signals involved in functional recovery. Four groups of adult female rats classified as (i) sham (SH) controls, (ii) subjected to a left C2 hemisection (C2H) only, (iii) C2H rats administered theophylline for 3 consecutive days 2 days after C2H (C2H-T Day 5) and (iv) C2H rats treated with theophylline for 3 consecutive days 2 days after C2H and then weaned for 12 days (C2H-T Day 17) prior to assessment of respiratory function and molecular analysis were employed. Corresponding Sham controls, C2H untreated (vehicle only controls) and C2H treated (theophylline) rats were sacrificed, C3-C6 spinal cord segments quickly dissected and left (ipsilateral) hemi spinal cord and right (contralateral) hemi spinal cord were separately harvested 2 days post surgery. SHAM operated and C2H untreated-controls corresponding to C2H-T Day 5 and C2H-T Day 17 rats, respectively, were prepared similarly. Messenger RNA levels for pro-inflammatory genes (TXNIP, IL-1β, TNF-α and iNOS) and neurotrophic and survival factors (BDNF, GDNF, and Bcl2) were analyzed by real time quantitative PCR. Gene expression pattern was unaltered in SH rats. TXNIP, iNOS, BDNF, GDNF and Bcl2 mRNA levels were significantly increased in the ipsilateral hemi spinal cord in C2H rats. BDNF, GDNF and Bcl2 levels remained elevated in the ipsilateral hemi spinal cord in C2H-T Day 5 rats. In this same group, there was further enhancement in TXNIP and IL-1β while iNOS returned to basal levels. Theophylline increased DNA binding activity of transcription factors - cyclic AMP responsive element (CRE) binding protein (CREB) and pro-inflammatory NF-κB. Messenger RNA levels for all genes returned to basal

  12. Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats

    PubMed Central

    Joseph, Vincent; Mamet, Julie; Lee, Fuchun; Dalmaz, Yvette; Van Reeth, Olivier

    2002-01-01

    The aim of this study was to test the hypothesis that prenatal hypoxia in rats might lead to consistent changes in the entrainment of the circadian clock by light. Pregnant female rats were placed in a chamber provided with hypoxic gas (10 % O2-90 % N2) at gestational day 5 and returned to normoxia before delivery. Once adult, rats born to hypoxic mothers had significant alterations in their circadian rhythm of locomotor activity (recorded in freely accessible running wheels). Under a regular 12/12 light/dark (LD) cycle, they showed a phase advance of their rhythm of activity (mean phase advance of 87 min) and were less active than control rats. After an abrupt 6 h phase delay in the LD cycle, rats from the prenatal hypoxic group (PNH) took significantly more time to resynchronise to the new LD cycle compared to controls (+53 %; 6.0 ± 1.5 vs. 9.2 ± 0.5 days respectively). Under constant darkness, PNH and control rats had a similar period of activity (24.27 ± 0.20 vs. 24.40 ± 0.13) but the response of PNH rats to a light pulse in the early subjective night was less marked than that of control rats (101 ± 9 vs. 158 ± 13 min). When submitted to acute restraint stress, PNH rats had a prolonged secretion of corticosterone compared to controls. These results indicate that prenatal hypoxia is a factor that has long lasting consequences for the functional output of the biological clock and the hormonal response to stress. PMID:12181309

  13. Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

    PubMed

    Garoui, El Mouldi; Troudi, Afef; Fetoui, Hamadi; Soudani, Nejla; Boudawara, Tahia; Zeghal, Najiba

    2012-11-01

    The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

  14. Noise exposure during early development influences the acoustic startle reflex in adult rats.

    PubMed

    Rybalko, Natalia; Bureš, Zbyněk; Burianová, Jana; Popelář, Jiří; Grécová, Jolana; Syka, Josef

    2011-03-28

    Noise exposure during the critical period of postnatal development in rats results in anomalous processing of acoustic stimuli in the adult auditory system. In the present study, the behavioral consequences of an acute acoustic trauma in the critical period are assessed in adult rats using the acoustic startle reflex (ASR) and prepulse inhibition (PPI) of ASR. Rat pups (strain Long-Evans) were exposed to broad-band noise of 125 dB SPL for 8 min on postnatal day 14; at the age of 3-5 months, ASR and PPI of ASR were examined and compared with those obtained in age-matched controls. In addition, hearing thresholds were measured in all animals by means of auditory brainstem responses. The results show that although the hearing thresholds in both groups of animals were not different, a reduced strength of the startle reflex was observed in exposed rats compared with controls. The efficacy of PPI in exposed and control rats was also markedly different. In contrast to control rats, in which an increase in prepulse intensity was accompanied by a consistent increase in the efficacy of PPI, the PPI function in the exposed animals was characterized by a steep increase in inhibitory efficacy at low prepulse intensities of 20-30 dB SPL. A further increase of prepulse intensity up to 60-70 dB SPL caused only a small and insignificant change of PPI. Our findings demonstrate that brief noise exposure in rat pups results in altered behavioral responses to sounds in adulthood, indicating anomalies in intensity coding and loudness perception.

  15. PROLONGED PERFORMANCE OF A HIGH REPETITION LOW FORCE TASK INDUCES BONE ADAPTATION IN YOUNG ADULT RATS, BUT LOSS IN MATURE RATS

    PubMed Central

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

    2015-01-01

    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 mo of age) and 14 young adult (2.5–6.5 mo 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

  16. 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.

  17. Social and non-social anxiety in adolescent and adult rats after repeated restraint.

    PubMed

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

    2009-06-22

    Adolescence is associated with potentially stressful challenges, and adolescents may differ from adults in their stress responsivity. To investigate possible age-related differences in stress responsiveness, the consequences of repeated restraint stress (90 min/day for 5 days) on anxiety, as indexed using the elevated plus-maze (EPM) and modified social interaction (SI) tests, were assessed in adolescent and adult Sprague-Dawley male and female rats. Control groups at each age included non-stressed and socially deprived animals, with plasma corticosterone (CORT) levels also measured in another group of rats on days 1 and 5 of stress (sampled 0, 30, 60, 90, and 120 min following restraint onset). While repeatedly restrained animals exhibited similar anxiety levels compared to non-stressed controls in the EPM, restraint stress increased anxiety at both ages in the SI test (as indexed by reduced social investigation and social preference). Daily weight gain measurements, however, revealed more marked stress-related suppression of body weight in adolescents versus adults. Analysis of stress-induced increases in CORT likewise showed that adolescents demonstrated less habituation than adults, embedded within typical sex differences in CORT magnitude (females greater than males) and age differences in CORT recovery (adolescents slower than adults). Despite no observable age-related differences in the behavioral response to restraint, adolescents were more sensitive to the repeated stressor in terms of physiological indices of attenuated weight gain and habituation of stress-induced CORT.

  18. 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.

  19. Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

    PubMed

    Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders.

  20. Electroconvulsive stimulation, but not chronic restraint stress, causes structural alterations in adult rat hippocampus--a stereological study.

    PubMed

    Olesen, Mikkel V; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress induces depression-like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress-induced depression-like behavior and increases neurogenesis. The total number of neurons and the granule cell layer volume was not affected by electroconvulsive stimulation.

  1. Perfluorooctane sulfonate effects on the reproductive axis in adult male rats.

    PubMed

    López-Doval, S; Salgado, R; Pereiro, N; Moyano, R; Lafuente, A

    2014-10-01

    Perfluorooctane sulfonate (PFOS) is a neurotoxic agent and it can disrupt the endocrine system activity. This work was undertaken to evaluate the possible effects of PFOS exposure on the hypothalamic-pituitary-testicular axis (HPT) in adult male rats, and to evaluate the possible morphological alterations induced by PFOS in the endocrine tissues of this axis. Adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, hypothalamic noradrenaline concentration increased in the anterior hypothalamus and in the median eminence, not changing in the mediobasal hypothalamus. PFOS treated rats presented a decrease of the gonadotropin releasing hormone (GnRH) gene expression, increasing the mRNA levels of the luteinizing hormone (LH) in rats treated with all doses administered except with the dose of 6 mg/kg/day. PFOS also induced a raise of the follicle stimulating hormone (FSH) gene expression in the animals exposed to 0.5 and 1.0 mg of PFOS/kg/day. After PFOS exposure, hypothalamic GnRH concentration was modified, LH and testosterone release was inhibited and FSH secretion was stimulated. Moreover, PFOS induced several histopathological alterations in the hypothalamus, pituitary gland and testis. The results obtained in the present study suggest in general terms that PFOS can inhibit the physiological activity of the reproductive axis in adult male rats, which could be explained, at least in part, by the structural alterations showed in the animals exposed to this chemical: very dense chromatin, condensed ribosomes and a loss of the morphology in the hypothalamus; a degeneration of the gonadotrophic cells, as well as a loss and degeneration of the spermatozoids and a very marked edema in the testis.

  2. 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

  3. Different forms of oestrogen rapidly upregulate cell proliferation in the dentate gyrus of adult female rats.

    PubMed

    Barha, C K; Lieblich, S E; Galea, L A M

    2009-03-01

    Oestrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. The dentate gyrus of the hippocampus retains the ability to produce neurones throughout adulthood and 17beta-oestradiol has been shown to influence hippocampal neurogenesis in adult female rats. The effects of other oestrogens, such as oestrone and 17alpha-oestradiol, on neurogenesis have not been investigated. The present study aimed to investigate the effects of 17beta-oestradiol, oestradiol benzoate, oestrone, and 17alpha-oestradiol on cell proliferation in ovariectomised adult female rats at two different time points. Young ovariectomised female rats were injected with one of the oestrogens at one of three doses. In Experiment 1, rats were exposed to the hormone for 4 h and, in Experiment 2, rats were exposed to the hormone for 30 min prior to 5-bromo-2-deoxyuridine injection to label proliferating cells and their progeny. We found that young ovariectomised females responded with increased cell proliferation to most oestrogens, except oestradiol benzoate, after 30 min of exposure. However, administration of oestrogens for a longer time interval was ineffective at increasing cell proliferation. After 30 min, 17beta-oestradiol and oestrone increased cell proliferation at low (0.3 microg) and high (10 microg) doses, whereas 17alpha-oestradiol increased cell proliferation at medium (1 microg) and high doses. The results of the present study indicate that different oestrogens rapidly increase cell proliferation in a dose-dependent manner, possibly through a nonclassical, nongenomic mechanism. Future experiments should focus on further elucidating the specific pathways utilised by each oestrogen. These results have important therapeutic implications because it may be possible to use 17alpha-oestradiol and lower doses of oestrogens in hormone replacement therapies.

  4. PRDM5 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat.

    PubMed

    Liu, Jie; Wu, Weijie; Hao, Jie; Yu, Mingchen; Liu, Jin; Chen, Xinlei; Qian, Rong; Zhang, Feng

    2016-12-01

    PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products that modulate cellular processes such as differentiation, cell growth and apoptosis. PRDM5 is a recently identified family member that functions as a transcriptional repressor and behaves as a putative tumor suppressor in different types of cancer. However, the expression and function of PRDM5 in spinal cord injury (SCI) are still unknown. In the present study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of PRDM5 expression in the spinal cord. We found that PRDM5 protein levels gradually increased, reaching a peak at day 5 and then gradually declined to a normal level at day 14 after SCI with Western blot analysis. Double immunofluorescence staining showed that PRDM5 immunoreactivity was found in neurons, astrocytes and microglia. However, the expression of PRDM5 was increased predominantly in neurons. Additionally, colocalization of PRDM5/active caspase-3 was been respectively detected in neurons. In vitro, we found that depletion of PRDM5 by short interfering RNA, obviously decreases neuronal apoptosis. In summary, this is the first description of PRDM5 expression in SCI. Our results suggested that PRDM5 might play crucial roles in CNS pathophysiology after SCI and this research will provide new drug targets for clinical treatment of SCI.

  5. Altered Cerebellar Circuitry following Thoracic Spinal Cord Injury in Adult Rats

    PubMed Central

    2016-01-01

    Cerebellar function is critical for coordinating movement and motor learning. However, events occurring in the cerebellum following spinal cord injury (SCI) have not been investigated in detail. We provide evidence of SCI-induced cerebellar synaptic changes involving a loss of granule cell parallel fiber input to distal regions of the Purkinje cell dendritic tree. This is accompanied by an apparent increase in synaptic contacts to Purkinje cell proximal dendrites, presumably from climbing fibers originating in the inferior olive. We also observed an early stage injury-induced decrease in the levels of cerebellin-1, a synaptic organizing molecule that is critical for establishing and maintaining parallel fiber-Purkinje cell synaptic integrity. Interestingly, this transsynaptic reorganizational pattern is consistent with that reported during development and in certain transgenic mouse models. To our knowledge, such a reorganizational event has not been described in response to SCI in adult rats. Regardless, the novel results of this study are important for understanding SCI-induced synaptic changes in the cerebellum, which may prove critical for strategies focusing on promoting functional recovery. PMID:27504204

  6. Regulation of neuropilin 1 by spinal cord injury in adult rats.

    PubMed

    Agudo, Marta; Robinson, Michelle; Cafferty, William; Bradbury, Elizabeth J; Kilkenny, Carol; Hunt, Stephen P; McMahon, Stephen B

    2005-03-01

    Using RT-PCR, in situ hybridization, Western blotting, and immunofluorescence, we have analyzed the expression of neuropilin 1 (Np1) in two models of spinal cord injury (spinal cord hemisection and dorsal column crush) and following dorsal root rhizotomy in adult rats. Our results show that Np1 RNA and protein are up-regulated in the spinal cord after all these lesions but remain unaltered in the adjacent dorsal root ganglia. In control animals, Np1 levels in the spinal cord are low and appear to be localized mainly in blood vessels, motoneurons, and in the superficial layers of the dorsal horn. After DCC and rhizotomy, Np1 is expressed de novo around the injury and in the deafferentated dorsal horn, respectively, mainly by OX42-positive microglial cells. Both lesions affect the sensory projections, and interestingly a consistent increase of Np1 signal is additionally seen in the dorsal horn where these projections terminate. Unexpectedly, this increase is bilateral after unilateral rhizotomy.

  7. Neuroanatomical distribution of galectin-3 in the adult rat brain.

    PubMed

    Yoo, Hong-Il; Kim, Eu-Gene; Lee, Eun-Jin; Hong, Sung-Young; Yoon, Chi-Sun; Hong, Min-Ju; Park, Sang-Jin; Woo, Ran-Sook; Baik, Tai-Kyoung; Song, Dae-Yong

    2017-04-01

    Galectin-3 is a member of the lectin subfamily that enables the specific binding of β-galactosides. It is expressed in a broad spectrum of species and organs, and is known to have various functions related to cell adhesion, signal transduction, and proinflammatory responses. Although, expression of galectin-3 in some activated neuroglia under neuroinflammation has been well documented in the central nervous system, little is known about the neuronal expression and distribution of galectin-3 in normal brain. To describe the cellular and neuroanatomical expression map of galectin-3, we performed galectin-3 immunohistochemistry on the entire normal rat brain and subsequently analyzed the neuronal distribution. Galectin-3 expression was observed not only in some neuroglia but also in neurons. Neuronal expression of galectin-3 was observed in many functional parts of the cerebral cortex and various other subcortical nuclei in the hypothalamus and brainstem. Neuroanatomical analysis revealed that robust galectin-3 immuno-signals were present in many hypothalamic nuclei related to a variety of physiological functions responsible for mediating anxiety responses, energy balance, and neuroendocrine regulation. In addition, the regions highly connected with these hypothalamic nuclei also showed intense galectin-3 expression. Moreover, multiple key regions involved in regulating autonomic functions exhibited high levels of galectin-3 expression. In contrast, the subcortical nuclei responsible for the control of voluntary motor functions and limbic system exhibited no galectin-3 immunoreactivity. These observations suggest that galectin-3 expression in the rat brain seems to be regulated by developmental cascades, and that functionally and neuroanatomically related brain nuclei constitutively express galectin-3 in adulthood.

  8. Neurones in the adult rat anterior medullary velum.

    PubMed

    Ibrahim, M; Menoud, P A; Celio, M R

    2000-03-27

    The presence of neurones in the rat anterior medullary velum (AMV) has been investigated by using antibodies to the calcium-binding proteins, parvalbumin (PV), calretinin (CR), and calbindin-D28k (CB). Disparate populations of mainly GABAergic neurones were located in the rostral and caudal regions of the AMV. The rostral region of the AMV was characterised by GABAergic CR-labelled or PV-labelled neurones. CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network. PV-labelled neurones had round somata (diameters between 6 and 10 microm) and were bi-tufted, with beaded dendrites. Both CR-labelled and PV-labelled dendrites formed punctate pericellular associations with unlabelled somatic profiles. In the caudal region of the AMV, PV-labelled neurones were GABAergic, multipolar cells, having round somata (diameters between 9 and 12 microm), with either beaded or nonbeaded dendrites forming a network of interconnecting dendrites. PV-labelled pericellular associations were made around both PV-labelled and unlabelled somatic profiles. CR labelled unipolar brush cells (UBCs) were not GABAergic. UBCs were characterised by a round to oval somata (10-15 microm in diameter) from which a single primary dendrite emerged to form a distal expansion having small terminal dendrites. From the distal expansion, there also appeared to be CR-labelled processes emanating and extending for up to 250 microm. CB occasionally labelled "Purkinje-like cells" (PLCs). The rat AMV is a more complex structure than first envisaged with the presence of predominantly inhibitory neurones expressing different calcium-binding proteins. Functional and anatomic aspects of this circuitry are further discussed.

  9. CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats.

    PubMed

    Das, Sutapa; Guha, Debjani

    2008-03-01

    Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.

  10. Use of the light/dark test for anxiety in adult and adolescent male rats.

    PubMed

    Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

    2013-11-01

    The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.

  11. Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.

    PubMed

    Guasti, Leonardo; Paul, Alex; Laufer, Ed; King, Peter

    2011-04-10

    Sonic hedgehog signaling was recently demonstrated to play an important role in murine adrenal cortex development. The organization of the rat adrenal differs from that of the mouse, with the zona glomerulosa and zona fasciculata separated by an undifferentiated zone in the rat, but not in the mouse. In the present study we aimed to determine the mRNA expression patterns of Sonic hedgehog and the hedgehog signaling pathway components Patched-1 and Gli1 in the developing and adult rat adrenal. Sonic hedgehog expression was detected at the periphery of the cortex in cells lacking CYP11B1 and CYP11B2 expression, while signal-receiving cells were localized in the overlying capsule mesenchyme. Using combined in situ hybridization and immunohistochemistry we found that the cells expressing Sonic hedgehog lie between the CYP11B2 and CYP11B1 layers, and thus Sonic hedgehog expression defines one cell population of the undifferentiated zone.

  12. 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.

  13. On Again, Off Again Effects of Gonadectomy on the Acoustic Startle Reflex in Adult Male Rats

    PubMed Central

    Turvin, J.C.; Messer, W.S.

    2007-01-01

    Numerous studies have shown sex and/or estrous cycle differences in the acoustic startle reflex (ASR) and its prepulse inhibition (PPI) in humans and animals. However, few have examined the effects of hormone manipulations on these behaviors. This study paired gonadectomy (GDX) in adult male rats with testing for ASR and PPI at 2, 4, 9, 16, 23, 30 and 37 days after surgery. Initial studies of control, GDX and GDX rats given testosterone propionate revealed no group differences in PPI, but did reveal phasic facilitation of the ASR in GDX rats that was greatest on the first and final testing sessions and that was attenuated by testosterone. A second study addressing roles for estrogen and androgen signaling tested new control and GDX rats along with GDX rats given estradiol or the non-aromatizable androgen, 5-alpha-dihydrotestosterone and revealed no group differences in PPI, and increases in ASR in GDX rats that were largest during the first and final testing sessions and that were attenuated by both hormone replacements. However, while responses in GDX rats given testosterone were similar to those of controls, ASR in estradiol- and to a lesser extent in dihydrotestosterone-treated GDX rats were typically lower than in controls. This may suggest that hormone modulation of the ASR requires synergistic estrogen and androgen actions. In the male brain where this can be achieved by local steroid metabolism, the enzymes responsible, e.g., aromatase, could help identify loci in the startle circuitry that may be especially relevant for the hormone modulation observed. PMID:17169383

  14. 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,...

  15. Leptin Attenuates the Contractile Function of Adult Rat Cardiomyocytes Involved in Oxidative Stress and Autophagy

    PubMed Central

    Luo, Liu-Jin; Liu, Ying-Ping; Yuan, Xun; Zhang, Gui-Ping; Hou, Ning; Wu, Xiao-Qian; Luo, Jian-Dong; Zhang, Gen-Shui

    2016-01-01

    Background Leptin has been identified as an important protein involved in obesity. As a chronic metabolic disorder, obesity is associated with a high risk of developing cardiovascular and metabolic diseases, including heart failure. The aim of this paper was to investigate the effects and the mechanism of leptin on the contractile function of cardiomyocytes in the adult rat. Methods Isolated adult rat cardiomyocytes were exposed to leptin (1, 10, and 100 nmol/L) for 1 hour. The calcium transients and the contraction of adult rat cardiomyocytes were recorded with SoftEdge MyoCam system. Apocynin, tempol and rapamycin were added respectively, and Western blotting was employed to evaluate the expression of LC3B and Beclin-1. Results The peak shortening and maximal velocity of shortening/relengthening (± dL/dtmax) of cell shortening were significantly decreased, and the time to 50% relengthening was prolonged with leptin perfusion. Leptin also significantly reduced the baseline, peak and time to 50% baseline of calcium transient. Leptin attenuated autophagy as indicated by decreased LC3-II and Beclin-1. All of the abnormalities were significantly attenuated by apocynin, tempol or rapamycin. Conclusions Our results indicated that leptin depressed the intracellular free calcium and myocardial systolic function via increasing oxidative stress and inhibiting autophagy. PMID:27899860

  16. Morphological alterations of central nervous system (CNS) myelin in vanadium (V)-exposed adult rats.

    PubMed

    García, Graciela B; Quiroga, Ariel D; Stürtz, Nelson; Martinez, Alejandra I; Biancardi, María E

    2004-08-01

    In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of vanadium in behavioral alterations and in brain lipid peroxidation was also investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days. Open field and rotarod tests were performed the day after the last dose had been administered and then animals were sacrificed by different methods for histological and lipid peroxidation studies. The present results show that intraperitoneal administration of V(+5) to adult rats resulted in changes in locomotor activity, specific myelin stainings and lipid peroxidation in some brain areas. They support the notion that CNS myelin could be a preferential target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms underlying this action could affect the myelin sheath leading to behavioral perturbations.

  17. Antipsychotic-induced suppression of locomotion in juvenile, adolescent and adult rats.

    PubMed

    Wiley, Jenny L

    2008-01-14

    Schizophrenia is a serious psychiatric disorder that is most frequently treated with the administration of antipsychotics. Although onset of schizophrenia typically occurs in late adolescence, the majority of preclinical research on the behavioral effects of antipsychotics and their mechanism(s) of action has been conducted on adult male animals. In this study, the acute effects of haloperidol (0.03-0.3 mg/kg, i.p.) and clozapine (1-10 mg/kg, i.p.) on locomotor activity were examined in juvenile [postnatal day 22 (PN22)], adolescent (PN40), and adult (>PN70) rats of both sexes. Subsequently, in order to determine whether tolerance to the activity suppressive effects of these drugs would occur in adolescents, PN40 rats were dosed and assessed for an additional nine days. While all groups exhibited some degree of suppression following acute administration of both drugs, juvenile rats were considerably more sensitive to this effect. With sub-chronic administration during late adolescent development (PN40-PN49), tolerance failed to develop. These results emphasize the importance of age in pharmacological characterization of antipsychotics and suggest that pre-adolescents may have enhanced sensitivity to the motor effects of these drugs. Further, they suggest that, similar to adults, older adolescents may not develop tolerance to the activity suppression induced by these two antipsychotics.

  18. 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.

  19. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    PubMed Central

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  20. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  1. Distribution of constitutively expressed MEF-2A in adult rat and human nervous systems.

    PubMed

    Ruffle, Rebecca A; Mapley, Andrew C; Malik, Manmeet K; Labruzzo, Salvatore V; Chabla, Janet M; Jose, Riya; Hallas, Brian H; Yu, Han-Gang; Horowitz, Judith M; Torres, German

    2006-06-15

    Myocyte enhancer factor 2A (MEF-2A) is a calcium-regulated transcription factor that promotes cell survival during nervous system development. To define and further characterize the distribution pattern of MEF-2A in the adult mammalian brain, we used a specific polyclonal antiserum against human MEF-2A to identify nuclear-localized MEF-2A protein in hippocampal and frontal cortical regions. Western blot and immunocytochemical analyses showed that MEF-2A was expressed not only in laminar structures but also in blood vessels of rat and human brains. MEF-2A was colocalized with doublecortin (DCX), a microtubule-associated protein expressed by migrating neuroblasts, in CA1 and CA2 boundaries of the hippocampus. MEF-2A was expressed heterogeneously in additional structures of the rat brain, including the striatum, thalamus, and cerebellum. Furthermore, we found a strong nuclear and diffuse MEF-2A labeling pattern in spinal cord cells of rat and human material. Finally, the neurovasculature of adult rats and humans not only showed a strong expression of MEF-2A but also labeled positive for hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channels. This study further characterizes the distribution pattern of MEF-2A in the mammalian nervous system, demonstrates that MEF-2A colocalizes with DCX in selected neurons, and finds MEF-2A and HCN1 proteins in the neurovasculature network.

  2. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    PubMed

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  3. Juvenile exposure to methamphetamine attenuates behavioral and neurochemical responses to methamphetamine in adult rats.

    PubMed

    McFadden, Lisa M; Carter, Samantha; Matuszewich, Leslie

    2012-04-01

    Previous research has shown that children living in clandestine methamphetamine (MA) labs are passively exposed to the drug [1]. The long-term effects of this early exposure on the dopaminergic systems are unknown, but may be important for adult behaviors mediated by dopamine, such as drug addiction. The current study sought to determine if juvenile exposure to low doses of MA would lead to altered responsiveness to the stimulant in adulthood. Young male and female rats (PD20-34) were injected daily with 0 or 2 mg/kg MA or left undisturbed and then tested at PD90. In the open field, adult rats exposed to MA during preadolescence had reduced locomotor activity compared to control non-exposed rats following an acute injection of MA (2 mg/kg). Likewise, methamphetamine-induced dopamine increases in the dorsal striatum were attenuated in male and female rats that had been exposed to MA as juveniles, although there were no changes in basal in vivo or ex vivo dopamine levels. These findings suggest that exposure of juveniles to MA leads to persistent changes in the behavioral and neurochemical responses to stimulants in adulthood.

  4. The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus

    PubMed Central

    Hradetzky, Eva; Sanderson, Thomas M; Tsang, Tsz M; Sherwood, John L; Fitzjohn, Stephen M; Lakics, Viktor; Malik, Nadia; Schoeffmann, Stephanie; O'Neill, Michael J; Cheng, Tammy MK; Harris, Laura W; Rahmoune, Hassan; Guest, Paul C; Sher, Emanuele; Collingridge, Graham L; Holmes, Elaine; Tricklebank, Mark D; Bahn, Sabine

    2012-01-01

    Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission, as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia. PMID:21956444

  5. Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats.

    PubMed

    Moreira, R M; Borges, P P; Lisboa, P C; Curty, F H; Moura, E G; Pazos-Moura, C C

    2000-09-01

    Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0. 25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro.

  6. Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.

    PubMed

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Ribeiro, Karine F; Petronilho, Fabrícia; Vuolo, Francieli; Colpo, Gabriela D; Pfaffenseller, Bianca; Kapczinski, Flávio; Dal-Pizzol, Felipe; Quevedo, João

    2013-04-01

    A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-α and IL-1β cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (p<0.05). Deprived rats treated with saline presented a decrease on BDNF levels in the amygdala (p<0.05), compared with all other groups. The IL-10 levels were decreased in the serum (p<0.05). TNF-α and IL-1β levels were increased in the serum and CSF of deprived rats treated with saline (p<0.05). Interestingly, imipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (p<0.05). Finally, these findings further support a relationship between immune activation, neurotrophins and the depression, and considering the action of imipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system.

  7. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    PubMed Central

    Eweka, Andrew Osayame; Eweka, Abieyuwa

    2010-01-01

    Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24), with average weight of 220g were randomly assigned into two treatments (A & B) of (n=16) and Control (c) (n=8) groups. The rats in the treatment groups (A & B) received 0.1g (500mg/kg body weight) and 0.2g (1000mg/kg body weight) of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c) received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings. PMID:22624138

  8. 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

  9. Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata.

    PubMed

    Li, Mingqiang; Nie, Lihong; Hu, Yajie; Yan, Xiang; Xue, Lian; Chen, Li; Zhou, Hua; Zheng, Yu

    2013-12-01

    The present experiments were carried out to investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of rats and effects of chronic intermittent hypoxia (CIH) on its expression. Sprague Dawley adult rats were randomly divided into two groups, including control (Con) group and CIH group. The endogenous production of hydrogen sulfide (H2S) in medulla oblongata tissue homogenates was measured using the methylene blue assay method, 3MST mRNA and protein expression were analyzed by RT-PCR and Western blotting, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of rats was investigated with immunohistochemical technique. CIH elevated the endogenous H2S production in rat medulla oblongata (P<0.01). The RT-PCR and Western blotting analyses showed that 3MST mRNA and protein were expressed in the medulla oblongata of rats and CIH promoted their expression (P<0.01). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N and Amb, but not in FN and NTS, were significantly increased in CIH group (P<0.05). In conclusion, 3MST exists in the neurons of medullary respiratory nuclei and its expression can be up-regulated by CIH in adult rat, suggesting that 3MST-H2S pathway may be involved in regulation of respiration and protection on medullary respiratory centers from injury induced by CIH.

  10. The alcohol-preferring (P) and high-alcohol-drinking (HAD) rats--animal models of alcoholism.

    PubMed

    McBride, William J; Rodd, Zachary A; Bell, Richard L; Lumeng, Lawrence; Li, Ting-Kai

    2014-05-01

    The objective of this article is to review the literature on the utility of using the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of rats in studies examining high alcohol drinking in adults and adolescents, craving-like behavior, and the co-abuse of alcohol with other drugs. The P line of rats meets all of the originally proposed criteria for a suitable animal model of alcoholism. In addition, the P rat exhibits high alcohol-seeking behavior, demonstrates an alcohol deprivation effect (ADE) under relapse drinking conditions, consumes amounts of ethanol during adolescence equivalent to those consumed in adulthood, and co-abuses ethanol and nicotine. The P line also exhibits excessive binge-like alcohol drinking, attaining blood alcohol concentrations (BACs) of 200 mg% on a daily basis. The HAD replicate lines of rats have not been as extensively studied as the P rats. The HAD1,2 rats satisfy several of the criteria for an animal model of alcoholism, e.g., these rats will voluntarily consume ethanol in a free-choice situation to produce BACs between 50 and 200 mg%. The HAD1,2 rats also exhibit an ADE under repeated relapse conditions, and will demonstrate similar levels of ethanol intake during adolescence as seen in adults. Overall, the P and HAD1,2 rats have characteristics attributed to an early onset alcoholic, and can be used to study various aspects of alcohol use disorders.

  11. IGF-I redirects doublecortin-positive cell migration in the normal adult rat brain.

    PubMed

    Maucksch, C; McGregor, A L; Yang, M; Gordon, R J; Yang, M; Connor, B

    2013-06-25

    The migration of subventricular zone (SVZ)-derived neural precursor cells through the rostral migratory stream (RMS) to the olfactory bulb is tightly regulated by local micro-environmental cues. Insulin-like Growth Factor-I (IGF-I) can stimulate the migration of several neuronal cell types and acts as a 'departure' factor in the avian SVZ. To establish whether IGF-I can also act as a migratory factor for adult neuronal precursor cells in vivo, in addition to its well established role in precursor cell proliferation and differentiation, we used AAV2-mediated gene transfer to produce ectopic expression of IGF-I in the normal adult rat striatum. We then assessed whether the expression of IGF-I would recruit SVZ-derived neuronal precursor cells from the RMS into the striatum. Ectopic expression of IGF-I in the normal adult rat brain significantly increased the number of doublecortin (Dcx)-positive cells and the extent of their migration into the striatum 4 and 8 weeks after AAV2-IGF-I injection but did not promote neuronal differentiation. In vitro migration assays confirmed that IGF-I is an inducer of migration and directs SVZ-derived adult neuronal precursor cell migration by both chemotaxis and chemokinesis. These results demonstrate that overexpression of IGF-I in the normal adult rat brain can override the normal cues directing precursor cell migration along the RMS and can redirect precursor cell migration into a non-neurogenic region. Enhanced expression of IGF-I following brain injury may therefore act as a diffusible factor mediating precursor cell migration to areas of neuronal cell damage.

  12. Chronic Paraspinal Muscle Injury Model in Rat

    PubMed Central

    Cho, Tack Geun; Kim, Young Baeg

    2016-01-01

    Objective The objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat. Methods Fifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations. Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers. Conclusion Our chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles. PMID:27651859

  13. Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase activity in pre-pubertal and adult rats.

    PubMed

    Marassi, Michelle P; Fortunato, Rodrigo S; da Silva, Alba C Matos; Pereira, Valmara S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia M Corrêa

    2007-01-01

    Iodothyronine deiodinase activities are regulated by sex steroids; however, the mechanisms underlying the reported sexual dimorphism are poorly defined. In the present report, we aimed to investigate whether type 1 deiodinase (D1) sexual dimorphism exists early in sexual development by studying pre-pubertal male (Pm) and female (Pf) rats, as well as adult controls (C) and gonadectomized male and females rats. Adult male Wistar rats were studied 21 days after orchiectomy (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher in pre-pubertal (P) rats than in the matching adults, with no difference between genders, although in adult males T3 was significantly lower than in females. There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal (P) rats was within the adult female range, and both were significantly lower than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult females, liver D1 activity was lower, while in adult males it was higher than in P rats. The same pattern of D1 activity was found in kidney. In thyroid and pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all significantly lower than in the adult male. There were no differences in serum T3 and T4 between C and Tex males, but serum TSH was significantly decreased in Tex rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes were detected in thyroid and pituitary. In Ovx females, T3 was significantly lower than in the C group. Serum T4 was significantly decreased by estradiol replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged. Eb replacement increased liver and thyroid D1 activity, but in the kidney, only the highest estradiol dose promoted a significant D1 increase. In conclusion, in males, hepatic and renal D1 activity appears to be significantly influenced by

  14. Ideal Experimental Rat Models for Liver Diseases.

    PubMed

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

  15. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  16. Excitation and inhibition jointly regulate cortical reorganization in adult rats.

    PubMed

    Benali, Alia; Weiler, Elke; Benali, Youssef; Dinse, Hubert R; Eysel, Ulf T

    2008-11-19

    The primary somatosensory cortex (SI) retains its capability for cortical reorganization after injury or differential use into adulthood. The plastic response of SI cells to peripheral stimulation is characterized by extension of cortical representations accompanied by changes of the receptive field size of neurons. We used intracortical microstimulation that is known to enforce local, intracortical synchronous activity, to induce cortical reorganization and applied immunohistochemical methods in the same individual animals to investigate how plasticity in the cortical topographic maps is linked to changes in the spatial layout of the inhibitory and excitatory neurotransmitter systems. The results reveal a differential spatiotemporal pattern of upregulation and downregulation of specific factors for an excitatory (glutamatergic) and an inhibitory (GABAergic) system, associated with changes of receptive field size and reorganization of the somatotopic map in the rat SI. Predominantly local mechanisms are the specific reduction of the calcium-binding protein parvalbumin in inhibitory neurons and the low expression of the activity marker c-Fos. Reorganization in the hindpaw representation and in the adjacent SI cortical areas (motor cortex and parietal cortex) is accompanied by a major increase of the excitatory transmitter glutamate and c-Fos. The spatial extent of the reorganization appears to be limited by an increase of glutamic acid decarboxylase and the inhibitory transmitter GABA. The local and medium-range net effects are excitatory and can facilitate receptive field enlargements and cortical map expansion. The longer-range increase of inhibition appears suited to limit these effects and to prevent neurons from pathological hyperexcitability.

  17. Perinatal exposure to xenoestrogens affects pain in adult female rats.

    PubMed

    Ceccarelli, Ilaria; Fiorenzani, Paolo; Della Seta, Daniele; Massafra, Cosimo; Cinci, Giuliano; Bocci, Anna; Aloisi, Anna Maria

    2009-01-01

    Estrogens have a variety of effects in addition to their action on reproductive structures, including permanent effects on the Central Nervous System (CNS). Therefore environmental chemicals with estrogenic activity (xenoestrogens) can potentially affect a number of CNS functions. In the present experiment, female rats receiving ethynylestradiol (EE) or methoxychlor (MXC) via the mothers during pregnancy (pre) or lactation (post) were tested in comparison with females born from mothers treated with OIL. The Object Recognition, Plantar and Formalin tests were carried out to evaluate the effects of these compounds on integrated functions such as memory and pain. Testosterone and estradiol plasma levels were determined by RIA. The results of the Object Recognition and Plantar tests did not differ among groups. However the groups differed in the Formalin test since flexing duration was higher in the EE- and MXC-pre groups than in the EE- and MXC-post and OIL groups. Estradiol plasma levels were higher in EE-pre than in the other groups. These results confirm the possibility that estrogen-like compounds (EE and MXC) can affect complex neural processes like pain when taken during critical stages of CNS development.

  18. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    PubMed

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults.

  19. A CONTROLLED SAFETY STUDY OF DIINDOLYLMETHANE IN THE IMMATURE RAT MODEL

    PubMed Central

    Elackattu, Alphi P.; Feng, Lining; Wang, Zhi

    2010-01-01

    OBJECTIVE Diindolylmethane, a natural product from cruciferous vegetables, has been shown to be a dietary component that has inhibitory effects on some tumors (e.g., laryngeal papilloma). However, current evidence to support its safety is based on adult humans or mature animals. There is little to show its safety in children. This study is designed to asses safety in the young rat model STUDY DESIGN Prospective Controlled Animal Study. METHODS 40 rats were separated into 4 treatment groups of 10 rats each, based on the amount of study drug they received in their daily food: 1. Immature rats fed low dose DIM, which is our proposed treatment dose (2.0mg/kg/day). 2. Immature rats fed high dose DIM (20.0mg/kg/day). 3. Immature rats fed no DIM (control). 4. Adult rats fed high dose DIM (20.0mg/kg/day). At the conclusion of the study we collected blood to compare serum chemistries and vitamin D levels, and harvest organs to observe for any gross or histological changes between the groups. Statistical methods involved one-way ANOVA and pairwise comparisons with Tukey’s multiple comparison adjustment. RESULTS Although our numbers do not allow for statistical significance, there was no appreciable difference in rat weights between the immature groups, nor was there appreciable difference between serum chemistries, or gross or histological examination of liver, kidney, or bone. CONCLUSIONS Diindolylmethane seems to have no adverse affects on the rat even when given in doses 10x what we propose to be therapeutic. This adds evidence to the safety of this drug in the pediatric population as a treatment option for recurrent respiratory papilloma. PMID:19544380

  20. Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats.

    PubMed

    Attella, M J; Hoffman, S W; Stasio, M J; Stein, D G

    1989-07-01

    Adult, male Sprague-Dawley rats received 100 mg/kg Ginkgo biloba extract (GBE) intraperitoneally for 30 days. GBE reduced overall activity and decreased sensitivity to light in the open field maze. The rats were also less responsive to noxious stimuli after 13 days of treatment with GBE. After the last injection, all subjects were trained on a delayed-spatial alternation task. Subsequent to acquisition of the spatial task, the rats received either sham operations and saline or bilateral frontal cortex lesions treated with either saline or GBE. Thirty additional days of treatment began on the day of injury, and open field behavior, analgesia, and metabolic activity measurements were again measured. The rats with lesions treated with saline were more active than their GBE-treated counterparts and sham controls but there were no differences in response to illumination or noxious stimuli. Retention of the delayed-spatial alternation indicated that rats with lesions treated with GBE were less impaired than brain-injured subjects receiving saline treatment. Histological examination showed that GBE reduced the extent of brain swelling in response to the injury.

  1. 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.

  2. Social interactions in adolescent and adult Sprague-Dawley rats: impact of social deprivation and test context familiarity.

    PubMed

    Varlinskaya, Elena I; Spear, Linda P

    2008-04-09

    Interactions with peers become particularly important during adolescence, and age differences in social interactions have been successfully modeled in rats. To determine the impact of social deprivation on social interactions under anxiogenic (unfamiliar) or non-anxiogenic (familiar) test circumstances during ontogeny, the present study used a modified social interaction test to assess the effects of 5 days of social isolation or group housing on different components of social behavior in early [postnatal day (P) 28], mid (P35), or late (P42) adolescent and adult (P70) male and female Sprague-Dawley rats. As expected, testing in an unfamiliar environment suppressed social interactions regardless of age, housing, and sex. Social deprivation drastically enhanced all forms of social behavior in P28 animals regardless of test situation, whereas depriving older animals of social interactions had more modest effects and was restricted predominantly to play fighting -- an adolescent-characteristic form of social interactions. Social investigation -- more adult-typical form of social behavior was relatively resistant to isolation-induced enhancement and was elevated in early adolescent isolates only. These findings confirm that different forms of social behavior are differentially sensitive to social deprivation across ontogeny.

  3. Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

    PubMed Central

    Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

    2014-01-01

    Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

  4. Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure.

    PubMed

    Gigante, Eduardo D; Santerre, Jessica L; Carter, Jenna M; Werner, David F

    2014-08-01

    Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults.

  5. Neonatal Administration of Memantine Enhances Social Cognition in Adult Rats Subjected to Early Maternal Deprivation

    PubMed Central

    Sánchez-Mendoza, Eduardo; Nieves, Nayadoleni; Merchor, Gustavo

    2016-01-01

    Schizophrenia is considered a neurodevelopmental disorder; however, all the available treatment options are used when the disease becomes clinically significant in adolescence or early adulthood. Using a developmental rat model of schizophrenia, we examined whether neonatal treatment with memantine, an NMDA receptor modulator, can improve schizophrenic-like symptoms in adulthood. Early maternal deprivation in rats produces deficits in social interaction behaviors in adulthood. In contrast, memantine administrated in neonatal rats subjected to early maternal deprivation significantly reduces deficits in social interaction behaviors in adulthood. These results raise the possibility that pharmacological treatment with memantine at the early developmental stage helps people with a risk to develop schizophrenic-like symptoms. PMID:28035183

  6. Developmental lead exposure impairs extinction of conditioned fear in young adult rats.

    PubMed

    McGlothan, Jennifer L; Karcz-Kubicha, Marzena; Guilarte, Tomás R

    2008-11-01

    Pavlovian fear conditioning is a model of emotional learning in which a neutral stimulus such as a tone is paired with an aversive stimulus such as a foot shock. Presentation of a tone with a foot shock in a context (test box) elicits a freezing response representative of stereotypic fear behavior. After conditioning has occurred, presentation of the context (test box) or tone in the absence of the unconditioned stimulus (shock) causes extinction of the fear response. Rats chronically exposed to environmentally relevant levels of lead (Pb(2+)) and controls were tested in a fear-conditioning (FC) paradigm at 50 days of age (PN50). Littermates to FC rats received an immediate shock (IS) when placed in the test box with no tone. Blood Pb(2+) levels in control and Pb(2+)-exposed animals were (mean+/-S.E.M.): 0.76+/-0.11 (n=15) and 25.8+/-1.28microg/dL (n=14). Freezing behavior was recorded during acquisition (day of training) or during 4 consecutive extinction days. Control and Pb(2+)-exposed FC rats exhibited the same level of freezing time on the acquisition day. No freezing behavior occurred in IS rats regardless of treatment. Presentation of context 24h later produced a freezing response on both control and Pb(2+)-exposed FC rats but not in IS rats. When tested in the extinction phase, Pb(2+)-exposed FC rats exhibited deficits in extinction compared to control FC rats. That is, when presented with context on 4 consecutive days after acquisition of the fear response, Pb(2+)-exposed FC rats exhibited a greater freezing response than control FC rats. These findings indicate that chronic Pb(2+) exposure produces a deficit in extinction learning and the animals remain more fearful than controls.

  7. Noise exposure during early development impairs the processing of sound intensity in adult rats.

    PubMed

    Bures, Zbynek; Grécová, Jolana; Popelár, Jirí; Syka, Josef

    2010-07-01

    During the early postnatal development of rats, the structural and functional maturation of the central auditory nuclei strongly relies on the natural character of the incoming neural activity. Even a temporary deprivation in the critical period results in a deterioration of neuronal responsiveness in adult animals. We demonstrate that besides the poorer frequency selectivity of neurons in the impaired animals reported previously [Grecova et al. (2009)Eur. J. Neurosci. 29, 1921-1930], the neuronal representation of sound intensity is significantly affected. Rate-intensity functions of inferior colliculus neurons were recorded in anaesthetized adult rats that were exposed to intense noise at postnatal day 14, and compared with those obtained in age-matched controls. Although the response thresholds were similar in the exposed and control rats, the neurons in the exposed animals had a longer first-spike latency, a narrower dynamic range, lower maximum response magnitudes and a steeper slope of the rate-intensity functions. The percentage of monotonic neurons was significantly lower in the exposed animals. The observed anomalies were confined to the mid- and high-frequency regions, whereas no significant changes were found in the low-frequency neurons. The altered parameters of the individual rate-intensity functions led also to differences in the cumulative responses. We conclude that a brief noise exposure during the critical period leads to a frequency-dependent alteration of the sound intensity representation in the inferior colliculus of adult rats. The results suggest that such impairments may appear in individuals with normal hearing thresholds, but with a history of noise exposure very early in childhood.

  8. Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

    PubMed

    Farag, Mahmoud M; Selima, Eman A; Salama, Mona A

    2013-11-15

    The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

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

    PubMed

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

    2015-07-08

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

  10. SEXUAL INTERACTIONS WITH UNFAMILIAR FEMALES REDUCE HIPPOCAMPAL NEUROGENESIS AMONG ADULT MALE RATS

    PubMed Central

    Spritzer, Mark D.; Curtis, Molly G.; DeLoach, Julia P.; Maher, Jack; Shulman, Leanne M.

    2016-01-01

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

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

    PubMed

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

    2016-03-24

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

  12. Chronic nicotine alters cannabinoid-mediated locomotor activity and receptor density in periadolescent but not adult male rats

    PubMed Central

    Werling, Linda L.; Reed, Stephanie Collins; Wade, Dean; Izenwasser, Sari

    2009-01-01

    A significant number of youths use cigarettes, and more than half of the youths who smoke daily also use illicit drugs. The focus of these studies is on how exposure to nicotine affects subsequent responses to both nicotine and cannabinoids in adolescents compared with adults. We have shown previously that chronic treatment with nicotine produces sensitization to its locomotor-activating effects in female and adult rats but not male adolescent rats. To better understand the effects of nicotine on adolescent and adult rats, rats were injected with nicotine or saline for 7 days and, on day 8, either challenged with delta-9-tetrahydrocannabinol (Δ9-THC) or the cannabinoid agonist CP 55,940 and tested for locomotor activity, or the brains were removed for quantitative autoradiography studies of the cannabinoid1 receptor. A separate group of rats was treated with nicotine plus the cannabinoid antagonist AM 251 and then challenged with CP 55,940. In adolescent male rats, nicotine administration led to sensitization to the locomotor-decreasing effects of both Δ9-THC and CP 55,940, but in adult male rats, the response to either drug was unchanged compared to controls. The effect of nicotine on CP 55,940-mediated locomotor activity was blocked by co-administration of AM 251 with the nicotine. Further, cannabinoid receptor density was increased in the prelimbic prefrontal cortex, ventral tegmental area, and select regions of the hippocampus in adolescent male rats pretreated with nicotine compared to vehicle-treated controls. There were no significant changes in cannabinoid receptor binding, however, in any of the brain regions examined in adult males pretreated with nicotine. The prelimbic prefrontal cortex and the hippocampus have been shown previously to be involved in stimulant reinforcement; thus it is possible that these changes contribute to the unique behavioral effects of chronic nicotine and subsequent drug administration in adolescents compared with adults. PMID

  13. Genetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala.

    PubMed

    McCoy, Chelsea R; Jackson, Nateka L; Day, Jeremy; Clinton, Sarah M

    2017-03-01

    Understanding biological mechanisms that shape vulnerability to emotional dysfunction is critical for elucidating the neurobiology of psychiatric illnesses like anxiety and depression. To elucidate molecular and epigenetic alterations in the brain that contribute to individual differences in emotionality, our laboratory utilized a rodent model of temperamental differences. Rats bred for low response to novelty (Low Responders, LRs) are inhibited in novel situations and display high anxiety, helplessness, and diminished sociability compared to High Novelty Responder (HR) rats. Our current transcriptome profiling experiment identified widespread gene expression differences in the amygdala of adult HR/LR rats; we hypothesize that HR/LR gene expression and downstream behavioral differences stem from distinct epigenetic (specifically DNA methylation) patterning in the HR/LR brain. Although we found similar levels of DNA methyltransferase proteins in the adult HR/LR amygdala, next-generation sequencing analysis of the methylome revealed 793 differentially methylated genomic sites between the groups. Most of the differentially methylated sites were hypermethylated in HR versus LR, so we next tested the hypothesis that enhancing DNA methylation in LRs would improve their anxiety/depression-like phenotype. We found that increasing DNA methylation in LRs (via increased dietary methyl donor content) improved their anxiety-like behavior and decreased their typically high levels of Forced Swim Test (FST) immobility; however, dietary methyl donor depletion exacerbated LRs' high FST immobility. These data are generally consistent with findings in depressed patients showing that treatment with DNA methylation-promoting agents improves depressive symptoms, and highlight epigenetic mechanisms that may contribute to individual differences in risk for emotional dysfunction.

  14. Evidence That the Periaqueductal Gray Matter Mediates the Facilitation of Panic-Like Reactions in Neonatally-Isolated Adult Rats

    PubMed Central

    Quintino-dos-Santos, Jeyce Willig; Müller, Cláudia Janaína Torres; Bernabé, Cristie Setúbal; Rosa, Caroline Azevedo; Tufik, Sérgio; Schenberg, Luiz Carlos

    2014-01-01

    Plenty of evidence suggests that childhood separation anxiety (CSA) predisposes the subject to adult-onset panic disorder (PD). As well, panic is frequently comorbid with both anxiety and depression. The brain mechanisms whereby CSA predisposes to PD are but completely unknown in spite of the increasing evidence that panic attacks are mediated at midbrain's dorsal periaqueductal gray matter (DPAG). Accordingly, here we examined whether the neonatal social isolation (NSI), a model of CSA, facilitates panic-like behaviors produced by electrical stimulations of DPAG of rats as adults. Eventual changes in anxiety and depression were also assessed in the elevated plus-maze (EPM) and forced-swimming test (FST) respectively. Male pups were subjected to 3-h daily isolations from post-natal day 2 (PN2) until weaning (PN21) allotting half of litters in individual boxes inside a sound-attenuated chamber (NSI, n = 26) whilst siblings (sham-isolated rats, SHAM, n = 27) and dam were moved to another box in a separate room. Non-handled controls (CTRL, n = 18) remained undisturbed with dams until weaning. As adults, rats were implanted with electrodes into the DPAG (PN60) and subjected to sessions of intracranial stimulation (PN65), EPM (PN66) and FST (PN67-PN68). Groups were compared by Fisher's exact test (stimulation sites), likelihood ratio chi-square tests (stimulus-response threshold curves) and Bonferroni's post hoc t-tests (EPM and FST), for P<0.05. Notably, DPAG-evoked panic-like responses of immobility, exophthalmus, trotting, galloping and jumping were markedly facilitated in NSI rats relative to both SHAM and CTRL groups. Conversely, anxiety and depression scores either did not change or were even reduced in neonatally-handled groups relative to CTRL, respectively. Data are the first behavioral evidence in animals that early-life separation stress produces the selective facilitation of panic-like behaviors in adulthood. Most importantly, results implicate

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

    SciTech Connect

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

    2012-03-09

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

  16. Gender differences in the effect of adult amphetamine on cognitive functions of rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Nohejlová, K; Slamberová, R

    2014-08-15

    Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure.

  17. Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats.

    PubMed

    Takeuchi, Takashi; Kitagawa, Hiroshi; Harada, Etsumori

    2004-05-01

    Using adult rats, the characteristic transporting system for lactoferrin (LF) from intestinal lumen into the blood circulation was investigated. The rats were randomly divided into two groups, a non-collected thoracic lymph (NC) group and a collected thoracic lymph (LC) group. Peripheral blood and thoracic lymph were collected from a jugular vein and a thoracic lymph duct, respectively, under anaesthesia. Bovine LF (bLF) was infused into the duodenal lumen by needle over a 1-min period at a dose of 1 g kg(-1). The transported bLF in the plasma and lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Morphological investigation was also carried out in the intestine, lymph node, and liver. Following intraduodenal administration of bLF, the transported bLF in the NC group was detected in the plasma, and reached a peak value at 2 h. Furthermore, the bLF concentration in the thoracic duct lymph fluid in the LC group increased significantly, and peaked 2 h after the administration. In addition, bLF was not detected in the plasma of the LC group. Immunohistochemical analysis clearly showed anti-bLF positive particles in the epithelial cells of the apical villi. The striated border and baso-lateral membrane were also bLF positive. These results suggest that intraduodenally infused bLF is transported into the blood circulation via the lymphatic pathway, not via portal circulation in adult rats.

  18. Lead Exposure Induces Weight Gain in Adult Rats, Accompanied by DNA Hypermethylation

    PubMed Central

    Zhao, Li; Li, Qin; Cang, Zhen; Chen, Chi; Lu, Meng; Cheng, Jing; Zhai, Hualing; Xia, Fangzhen; Ye, Lin; Lu, Yingli

    2017-01-01

    Objective Previous studies have revealed the association of lead (Pb) exposure with obesity. DNA methylation alteration has been suggested to be one of the regulatory mechanisms of obesity. We aimed to explore whether Pb exposure is related with weight gain and DNA methylation alteration. Methods Male adult 8 week Wistar rats were divided into 5 groups: the normal chow diet (NCD); the NCD+0.05%Pb; the NCD+0.15%Pb; the NCD+0.45%Pb and the high fat diet. Rats were exposed to different dosages of Pb through drinking water for 21 weeks. Body weight, fasted blood glucose level, fasted insulin level, homeostasis assessment of insulin resistance (HOMA-IR) index and lipid profile were detected. Intra-peritoneal glucose tolerance test (IPGTT) was constructed to evaluate the glucose tolerance. Lipid accumulation of liver was detected and liver DNA underwent whole genome bisulfite sequencing. Results The NCD+0.05%Pb group had significantly greater weight, HOMA-IR and triglycerides, and lower glucose intolerance than the NCD group (P <0.05). This group also showed hepatic lipid accumulation. These metabolic changes were not observed in the other two Pb dosage groups. Furthermore, DNA hypermethylation extended along pathways related to glucose and lipid metabolism in NCD+0.05%Pb group. Conclusion Pb exposure resulted in dose-specific weight gain in adult Wistar rats, accompanied by alteration of DNA methylation. PMID:28107465

  19. Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.

    PubMed

    Ivy, G O; Gould, H J; Killackey, H P

    1984-07-23

    Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.

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

    PubMed

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

    1982-07-01

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

  1. Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat.

    PubMed

    Bonomo, Isabela Teixeira; Lisboa, Patrícia Cristina; Passos, Magna Cottini Fonseca; Alves, Simone Bezerra; Reis, Adelina Martha; de Moura, Egberto Gaspar

    2008-08-01

    Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum tri-iodothyronine (T(3)). Maternal hypoprolactinemia at the end of lactation caused higher body weight in adult life, suggesting an association between maternal prolactin (PRL) level and programming of the offspring's adult body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD), liver and pituitary de-iodinase activities (D1 and/or D2), and in vitro post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into BRO - injected with 1 mg/twice a day, daily for the last 3 days of lactation, and C - control, saline-injected with the same frequency. At 180 days of age, the offspring were injected with (125)I i.p. and after 2 h, they were killed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (-51%), T(3) (-23%), and thyroxine (-21%), lower thyroid (125)I uptake (-41%), liver mGPD (-55%), and pituitary D2 (-51%) activities, without changes in the in vitro post-TRH TSH release. We show that maternal PRL suppression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.

  2. Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

    PubMed Central

    Merkley, Christina M.; Jian, Charles; Mosa, Adam; Tan, Yao-Fang; Wojtowicz, J. Martin

    2014-01-01

    Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age. PMID:25071426

  3. Functional plasticity of regenerated and intact taste receptors in adult rats unmasked by dietary sodium restriction.

    PubMed

    Hill, D L; Phillips, L M

    1994-05-01

    Unilateral chorda tympani nerve sectioning was combined with institution of a sodium-restricted diet in adult rats to determine the role that environment has on the functional properties of regenerating taste receptor cells. Rats receiving chorda tympani sectioning but no dietary manipulation (cut controls) and rats receiving only the dietary manipulation (diet controls) had normal responses to a concentration series of NaCl, sodium acetate (NaAc), and NH4Cl. However, responses from the regenerated nerve in NaCl-restricted rats (40-120 d postsectioning) to NaCl and NaAc were reduced by as much as 30% compared to controls, indicating that regenerating taste receptors are influenced by environmental (dietary) factors. Responses to NH4Cl were normal; therefore, the effect appears specific to sodium salts. Surprisingly, in the same rats, NaCl responses from the contralateral, intact chorda tympani were up to 40% greater than controls. Thus, in the same rat, there was over a twofold difference in sodium responses between the right and left chorda tympani nerves. A study of the time course of the functional alterations in the intact nerve revealed that responses to NaCl were extremely low immediately following sectioning (about 20% of the normal response), and then increased monotonically during the following 50 d until relative response magnitudes became supersensitive. This function occurred even when the cut chorda tympani was prevented from reinnervating lingual epithelia, demonstrating that events related to regeneration do not play a role in the functional properties of the contralateral side of the tongue.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    PubMed

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  5. Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

    PubMed

    Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G

    1983-01-01

    Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

  6. Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats

    PubMed Central

    Park, Mi-Sook; Oh, Hyean-Ae; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Sang-Hoon; Kim, Chang-Ju; Kim, Hyun-Bae; Kim, Hong

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage. PMID:25061593

  7. Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats.

    PubMed

    Park, Mi-Sook; Oh, Hyean-Ae; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Sang-Hoon; Kim, Chang-Ju; Kim, Hyun-Bae; Kim, Hong

    2014-06-01

    Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage.

  8. Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs)

    SciTech Connect

    Ostrow, Lyle W.; Suchyna, Thomas M.; Sachs, Frederick

    2011-06-24

    Highlights: {yields} Endothelin-1 expression by adult rat astrocytes correlates with cell proliferation. {yields} Stretch-induced ET-1 is inhibited by GsMtx-4, a specific inhibitor of Ca{sup 2+} permeant SACs. {yields} The less specific SAC inhibitor streptomycin also inhibits ET-1 secretion. {yields} Stretch-induced ET-1 production depends on a calcium influx. {yields} SAC pharmacology may provide a new class of therapeutic agents for CNS pathology. -- Abstract: The expression of endothelins (ETs) and ET-receptors is often upregulated in brain pathology. ET-1, a potent vasoconstrictor, also inhibits the expression of astrocyte glutamate transporters and is mitogenic for astrocytes, glioma cells, neurons, and brain capillary endothelia. We have previously shown that mechanical stress stimulates ET-1 production by adult rat astrocytes. We now show in adult astrocytes that ET-1 production is driven by calcium influx through stretch-activated ion channels (SACs) and the ET-1 production correlates with cell proliferation. Mechanical stimulation using biaxial stretch (<20%) of a rubber substrate increased ET-1 secretion, and 4 {mu}M GsMTx-4 (a specific inhibitor of SACs) inhibited secretion by 30%. GsMTx-4 did not alter basal ET-1 levels in the absence of stretch. Decreasing the calcium influx by lowering extracellular calcium also inhibited stretch-induced ET-1 secretion without effecting ET-1 secretion in unstretched controls. Furthermore, inhibiting SACs with the less specific inhibitor streptomycin also inhibited stretch-induced ET-1 secretion. The data can be explained with a simple model in which ET-1 secretion depends on an internal Ca{sup 2+} threshold. This coupling of mechanical stress to the astrocyte endothelin system through SACs has treatment implications, since all pathology deforms the surrounding parenchyma.

  9. Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

    PubMed Central

    Shepherd, Daniel J.; Tsai, Shih-Yen; O'Brien, Timothy E.; Farrer, Robert G.; Kartje, Gwendolyn L.

    2016-01-01

    Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis. PMID:27803646

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

    PubMed Central

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

    2015-01-01

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

  11. Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats.

    PubMed

    Doremus-Fitzwater, Tamara L; Spear, Linda P

    2011-08-01

    Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% wt/vol) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-s presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age.

  12. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex123

    PubMed Central

    Beshara, Simon; Beston, Brett R.; Pinto, Joshua G. A.

    2015-01-01

    Abstract Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity. PMID:26730408

  13. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex.

    PubMed

    Beshara, Simon; Beston, Brett R; Pinto, Joshua G A; Murphy, Kathryn M

    2015-01-01

    Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity.

  14. 11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis.

    PubMed

    Maya, Yoshifumi; Werner, Rudolf A; Schütz, Claudia; Wakabayashi, Hiroshi; Samnick, Samuel; Lapa, Constantin; Zechmeister, Christina; Jahns, Roland; Jahns, Valérie; Higuchi, Takahiro

    2016-12-01

    Myocarditis represents a major cause of dilated cardiomyopathy and sudden cardiac death in younger adults. Currently, definitive diagnosis of myocarditis requires endomyocardial biopsy, which is highly invasive and has the drawback of variable sensitivity due to inherent sampling error. Therefore, reliable noninvasive methods to detect and monitor cardiac inflammation are clinically relevant. In this study, we explored the potential of radiolabeled methionine to assess myocardial inflammatory activity in a rat model of experimental autoimmune myocarditis (EAM).

  15. Maternal isobutyl-paraben exposure alters anxiety and passive avoidance test performance in adult male rats.

    PubMed

    Kawaguchi, Maiko; Irie, Kaoru; Morohoshi, Kaori; Watanabe, Gen; Taya, Kazuyoshi; Morita, Masatoshi; Kondo, Yasuhiko; Imai, Hideki; Himi, Toshiyuki

    2009-10-01

    Isobutyl-paraben (IBP), one of the most widely used preservatives, exhibits estrogenic activity. In this study, we analyzed the effects of maternal IBP treatment on the emotional behavior and learning performance in mature offspring. Pregnant female Sprague-Dawley rats were treated with IBP via a subcutaneous Silastic capsule. Consequently, the offspring were exposed to IBP during gestation through the placentae, and before weaning through the milk. Male and female offspring were tested for emotional behavior in an open field and in an elevated plus maze at five and six weeks old, respectively. IBP-exposed male (but not female) rats spent less time in the open arms of the elevated plus maze. At 11 weeks old, all females were gonadectomized and treated chronically with 17beta-estradiol or cholesterol by Silastic capsules; all males were kept intact. They were tested for learning performance in a passive avoidance test and a Morris water maze. IBP exposure impaired the performance of males in the passive avoidance test. These findings suggest that male rats are more affected by early exposure to IBP than female rats. IBP affects their adult behavior including anxiety and learning abilities.

  16. Spermatogenetic disorders in adult rats exposed to tributyltin chloride during puberty.

    PubMed

    Yu, Wook Joon; Lee, Beom Jun; Nam, Sang Yoon; Kim, Young Chul; Lee, Yong Soon; Yun, Young Won

    2003-12-01

    Adverse effects of tributyltin (TBT) chloride were investigated on the reproductive system in male adult rats as exposed during puberty. Fifty Sprague-Dawley rats at the age of 35 days were assigned to five different groups: negative control receiving vehicle, methyltestosterone (10 mg/kg B.W.), and TBT chloride treatments (5, 10, and 20 mg/kg B.W.). Animals were treated by oral gavage for ten consecutive days and sacrificed at 5 weeks after final treatment. The treatment of TBT chloride at the high dose of 20 mg/kg B.W. significantly decreased homogenization-resistant testicular sperm counts (p<0.05). The TBT chloride treatment at the doses of 10 and 20 mg/kg B.W. also significantly decreased caudal epididymal sperm counts (p<0.01). Some of motion kinematic parameters (motility, mean angular displacement, lateral head displacement, and dance) of sperms retrieved from vasa deference were significantly decreased in rats treated with the TBT chloride at the dose of 20 mg/kg B.W. (p<0.05). These results provide a further evidence that an exposure to TBT chloride during pubertal period in male rats produces spermatogenic disorders characterized by decreasing testicular and epididymal sperm counts and some motion parameters of sperms in the vasa deference.

  17. Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex of adult rats.

    PubMed

    Bortel, Aleksandra; Nowak, Przemyslaw; Brus, Ryszard

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a noradrenergic neurotoxin which selectively damages noradrenergic projections originating from the locus coeruleus (LC). DSP-4 treatment of rats on the first and third days after birth produces a long-lasting lesion of noradrenergic neurons in the prefrontal cortex (PFC). In DSP-4-lesioned rats, studied as adults, we observed a decrease in norepinephrine content, with no significant change in the levels of dopamine, 5-hydroxytryptamine, and gamma-aminobutyric acid (GABA). There is now a well established interaction between noradrenergic and GABAergic systems, whereby the noradrenergic system is involved in the regulation of basal GABA release, while GABAergic neurons simultaneously exert tonic inhibitory regulation of LC norepinephrine neurons. We examined GABAergic neurotransmission in the norepinephrine-denervated PFC for a better appreciation of the interaction between these two systems. Treatment with the GABA transaminase inhibitor vigabatrine (VGB) increased the GABA level of PFC (tissue content) in both intact and lesioned groups. Additionally, VGB increased extracellular GABA concentration in the PFC in both control and DSP-4-lesioned animals, but the elevation of GABA was 2-fold higher in DSP-4 lesioned rats. These findings indicate that neonatal DSP-4 treatment increases GABAergic neurotransmission in the PFC of rats in adulthood, perhaps by decreasing reactivity of central GABA(A) receptors.

  18. Effects of estradiol and progesterone on vertebral collagen, glycosaminoglycans and phosphatases in ovariectomized adult rats.

    PubMed

    Gopala Krishnan, V; Arunakaran, J; Govindarajulu, P; Srinivasan, N

    2003-03-01

    Vertebral collagen, glycosaminoglycans (GAGs), tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were measured in ovariectomized (ovx) adult Wistar rats treated with estradiol (E 2 ) (10 micro g/kg BW for 35 days on alternate days, and progesterone (P 4 ) (140 micro g/kg BW for 35 days on alternate days) in E 2 + P 4 treated rats. P 4 given alone or in combination with E 2 significantly increased the levels of collagen in the vertebral bone. Neither ovx nor E 2 treatment altered the concentration of collagen in these rats. Administration of E 2 or P 4 significantly decreased the concentration of hyaluronic acid (HA), but remaining unaffected when a combination of these steroids was given. In contrast to their effect on HA, E 2 and P 4 each significantly increased the levels of chondroitin sulfate (CS) in the vertebral bone. The specific activity of ALP was decreased after ovx. E 2 and P 4 alone or in combination also registered a significant decrease in the activities of ALP and TRAP. The results suggest that E 2 and P 4 each exert definite effects on vertebral bone turnover in ovariectomized rats.

  19. Tianeptine facilitates spreading depression in well-nourished and early-malnourished adult rats.

    PubMed

    Amancio-Dos-Santos, Angela; Maia, Luciana Maria Silva de Seixas; Germano, Paula Catirina Pereira da Silva; Negrão, Yleana Danielle Dos Santos; Guedes, Rubem Carlos Araújo

    2013-04-15

    Nutritional status during development can modify the brain's electrophysiological properties and its response to drugs that reduce the serotonin availability in the synaptic cleft. Here we used cortical spreading depression (CSD) in the rat as a neurophysiological parameter to investigate the interaction between nutritional status and treatment with tianeptine, a serotonin uptake enhancer. From postnatal day 2 to 24, well-nourished and early-malnourished rat pups were s.c. injected with tianeptine (5 or 10mg/kg; 10 ml/kg) or equivalent volume of saline solution (control group). When the animals were 25-30 days old, CSD was recorded on the brain cortical surface. In the well-nourished rats, but not in the malnourished group, systemic tianeptine dose-dependently increased the CSD propagation velocity, with 10mg/kg producing a significant (P<0.05) effect. An experiment in adult rats showed that cortical topical application of tianeptine solutions (5mg/ml, 10mg/ml, and 20mg/ml) increased the CSD propagation in both the well-nourished and early-malnourished conditions. In well-nourished animals, 0.5mg/ml topical tianeptine did not affect CSD propagation, and 2mg/ml produced a small, but significant CSD acceleration. Our results indicate a facilitating action of tianeptine on CSD propagation, probably via tianeptine's pharmacological action on the serotonin system. These findings support previous data suggesting an antagonistic role of the serotoninergic system on CSD.

  20. The emerging role for rat models in gene discovery

    PubMed Central

    Dwinell, Melinda R.; Lazar, Jozef; Geurts, Aron M.

    2011-01-01

    Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review, we will briefly outline the rat models, bioinformatic tools, and technologies that are changing the landscape of translational research. The strategies used to translate disease traits to genes to function, and ultimately, to improve human health will be discussed. Finally, our perspectives on how rat models will continue to positively impact biomedical research will be provided. PMID:21732192

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

    PubMed Central

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

    2015-01-01

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

  2. Neonatal Nicotine Exposure Leads to Hypothalamic Gliosis in Adult Overweight Rats.

    PubMed

    Younes-Rapozo, V; Moura, E G; Manhães, A C; Pinheiro, C R; Carvalho, J C; Barradas, P C; de Oliveira, E; Lisboa, P C

    2015-12-01

    Astrocytes and microglia, the immune competent cells of central nercous system, can be activated in response to metabolic signals such as obesity and hyperleptinaemia. In rats, maternal exposure to nicotine during lactation leads to central obesity, hyperleptinaemia, leptin resistance and alterations in hypothalamic neuropeptides in the offspring during adulthood. In the present study, we studied the activation of astrocytes and microglia, as well as the pattern of inflammatory mediators, in adult offspring of this experimental model. On postnatal day 2 (P2), osmotic minipumps releasing nicotine (NIC) (-6 mg/kg/day) or saline for 14 days were s.c. implanted in dams. Male offspring were killed on P180 and hypothalamic immunohistochemistry, retroperitoneal white adipose tissue (WAT) polymerase chain reaction analysis and multiplex analysis for plasma inflammatory mediators were carried out. At P180, NIC astrocyte cell number was higher in the arcuate nucleus (ARC) (medial: +82%; lateral: +110%), in the paraventricular nucleus (PVN) (+144%) and in the lateral hypothalamus (+121%). NIC glial fibrillary acidic protein fibre density was higher in the lateral ARC (+178%) and in the PVN (+183%). Interleukin-6 was not affected in the hypothalamus. NIC monocyte chemotactic protein 1 was only higher in the periventricular nucleus (+287%). NIC microglia (iba-1-positive) cell number was higher (+68%) only in the PVN, as was the chemokine (C-X3-C motif) receptor 1 density (+93%). NIC interleukin-10 was lower in the WAT (-58%) and plasma (-50%). Thus, offspring of mothers exposed to nicotine during lactation present hypothalamic astrogliosis at adulthood and microgliosis in the PVN.

  3. The effect of methylphenidate and rearing environment on behavioral inhibition in adult male rats

    PubMed Central

    Hill, Jade C.; Covarrubias, Pablo; Terry, Joel; Sanabria, Federico

    2012-01-01

    Rationale The ability to withhold reinforced responses—behavioral inhibition—is impaired in various psychiatric conditions including Attention Deficit Hyperactivity Disorder (ADHD). Methodological and analytical limitations have constrained our understanding of the effects of pharmacological and environmental factors on behavioral inhibition. Objectives To determine the effects of acute methylphenidate (MPH) administration and rearing conditions (isolated vs. pair-housed) on behavioral inhibition in adult rats. Methods Inhibitory capacity was evaluated using two response-withholding tasks, differential reinforcement of low rates (DRL) and fixed minimum interval (FMI) schedules of reinforcement. Both tasks made sugar pellets contingent on intervals longer than 6 s between consecutive responses. Inferences on inhibitory and timing capacities were drawn from the distribution of withholding times (interresponse times, or IRTs). Results MPH increased the number of intervals produced in both tasks. Estimates of behavioral inhibition increased with MPH dose in FMI and with social isolation in DRL. Nonetheless, burst responding in DRL and the divergence of DRL data relative to past studies, among other limitations, undermined the reliability of DRL data as the basis for inferences on behavioral inhibition. Conclusions Inhibitory capacity was more precisely estimated from FMI than from DRL performance. Based on FMI data, MPH, but not a socially enriched environment, appears to improve inhibitory capacity. The highest dose of MPH tested, 8 mg/kg, did not reduce inhibitory capacity but reduced the responsiveness to waiting contingencies. These results support the use of the FMI schedule, complemented with appropriate analytic techniques, for the assessment of behavioral inhibition in animal models. PMID:22057663

  4. Chronic morphine exposure during puberty decreases postpartum prolactin secretion in adult female rats.

    PubMed

    Byrnes, Elizabeth M

    2005-03-01

    Opiate use in teenage populations has been increasing in recent years. The potential impact of exposure to high levels of opiates at a time when reproductive systems are maturing has not been well studied, especially in females. The present study used an animal model of adolescent opiate abuse in females to examine the potential impact of high levels of opiates during puberty on several reproductive parameters, including suckling-induced prolactin secretion. Two groups of juvenile female rats were administered increasing doses of morphine sulfate or saline (s.c.) from age 30-50 days, beginning with a dose of 2.5 mg/kg and achieving a maximal dose of 50 mg/kg. As adults, these females were mated and reared either their own or foster pups. On either postpartum day 5 or 10, following a 4 h separation, suckling-induced prolactin secretion was measured. In addition, on postpartum day 5 maternal behavior latencies were determined. The results demonstrate reduced suckling-induced prolactin secretion on postpartum day 5 in females previously exposed to morphine during pubertal development. These effects were observed in females rearing either their own or fostered pups. These effects were not due to any differences in maternal behavior latencies, as retrieval or crouching latencies were unaffected. In summary, chronic morphine exposure during puberty results in changes in the regulation of prolactin secretion during early lactation, which are observed several weeks after cessation of drug treatment. These data suggest that prior opiate use during puberty can continue to affect the regulation of prolactin secretion into adulthood.

  5. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

    PubMed

    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

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

    PubMed

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

    2014-12-14

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

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

    PubMed

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

    2015-03-01

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

  8. Intestinal mast cells and eosinophils in relation to Strongyloides ratti adult expulsion from the small and large intestines of rats.

    PubMed

    Shintoku, Y; Kadosaka, T; Kimura, E; Takagi, H; Kondo, S; Itoh, M

    2013-04-01

    Mucosal mast cells (MMC) play a crucial role in the expulsion of Strongyloides ratti adults from the small intestine of mice. We reported the large intestinal parasitism of S. ratti in rats, and there has been no report on MMC in the large intestine of the natural host. We studied kinetics of MMC, together with eosinophils, in the upper and lower small intestines, caecum and colon of infected rats. Two distinct phases of mastocytosis were revealed: one in the upper small intestine triggered by stimulation of 'ordinary' adults, and the other in the colon stimulated by 'immune-resistant' adults that started parasitizing the colon around 19 days post-infection. In all 4 intestinal sites, the MMC peaks were observed 5-7 days after the number of adult worms became the maximum and the height of MMC peaks appeared to be dependent on the number of parasitic adults, suggesting an important role played by worms themselves in the MMC buildup.

  9. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    PubMed

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats.

  10. Stress-induced suppression of hippocampal neurogenesis in adult male rats is altered by prenatal ethanol exposure

    PubMed Central

    SLIWOWSKA, J. H.; BARKER, J. M.; BARHA, C. K.; LAN, N.; WEINBERG, J.; GALEA, L. A. M.

    2016-01-01

    In adulthood, both alcohol (ethanol) and stress are known to suppress hippocampal neurogenesis in male rats. Similarly, most studies report that prenatal alcohol exposure (PAE) reduces cell proliferation and/or cell survival in the hippocampus of adult males. Furthermore, PAE is known to have marked effects on behavioral and hypothalamic–pituitary–adrenal (HPA) responsiveness to stressors. However, no studies have examined the modulation of adult hippocampal neurogenesis by stress in PAE animals. We hypothesized that, in accordance with previous data, PAE would suppress basal levels of adult hippocampal neurogenesis, and further that stress acting on a sensitized HPA axis would have greater adverse effects on adult hippocampal neurogenesis in PAE than in control rats. Adult male offspring from PAE, pair-fed (PF) control, and ad libitum-fed control (C) groups were subjected to restraint stress (9 days, 1 h/day) or left undisturbed. Rats were then injected with bromodeoxyuridine (BrdU) on day 10, perfused 24 h (proliferation) or 3 weeks (survival) later, and brains processed for BrdU immunohistochemistry. We found that (1) under non-stressed conditions, PAE rats had a small but statistically significant suppressive effect on levels of hippocampal neurogenesis and (2) unexpectedly, repeated restraint stress significantly reduced neurogenesis in C and PF, but not PAE rats. We speculate that the failure of PAE males to mount an appropriate (i.e. suppressive) neurogenic response to stressors, implies reduced plasticity and adaptability or resilience, which could impact negatively on hippocampal structure and function. PMID:20536332

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

    PubMed

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

    2013-06-01

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

  12. Effect of Ozone on Intestinal Epithelial Homeostasis in a Rat Model

    PubMed Central

    Sukhotnik, Igor; Starikov, Alona; Coran, Arnold G.; Pollak, Yulia; Sohotnik, Rima; Shaoul, Ron

    2015-01-01

    Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model. Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 mL of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 mL of ozone/oxygen mixture by gavage and 2 mL of water IP for 5 days; 3) O3-IP rats were treated with 2 mL of water by gavage and 2 mL of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice. Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover. Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat model. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration. PMID:25717388

  13. Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults.

    PubMed

    Hori, S E; Powell, K J; Robertson, G S

    2007-01-05

    Recognition memory was assessed in adult rats that received bilateral injections of saline (sham lesions) or ibotenic acid (lesioned) in the ventral hippocampus as neonates (postnatal day 7, PD7) or young adult (42 days of age, PD42) using the Novel Object Recognition Test (NORT). Normal or sham-lesioned rats were able to distinguish novel from familiar objects over a 0.5 and 2 h delay between the sample and choice phases. Adult rats (PD70) lesioned as neonates performed progressively worse than sham-lesioned animals at delays of 0.5 and 2 h. A single injection of darbepoetin alfa (500 or 5000 U/kg, i.p.), given 1 h before the sample phase restored performance 0.5 or 2 h later in the choice phase to same levels as sham-lesioned rats. Adults lesioned on PD42 displayed deficits in NORT performance with a 2 h delay between the choice and sample phases that were completely reversed by administration of darbepoetin alfa (5000 U/kg, i.p.) 1 h before the sample phase. These results suggest that darbepoetin alfa may have utility in treating memory deficits associated with brain dysfunction related to developmental disorders such as schizophrenia.

  14. Sox9 modulates cell survival and adipogenic differentiation of multipotent adult rat mesenchymal stem cells.

    PubMed

    Stöckl, Sabine; Bauer, Richard J; Bosserhoff, Anja K; Göttl, Claudia; Grifka, Joachim; Grässel, Susanne

    2013-07-01

    Sox9 is a key transcription factor in early chondrogenesis with distinct roles in differentiation processes and during embryonic development. Here, we report that Sox9 modulates cell survival and contributes to the commitment of mesenchymal stem cells (MSC) to adipogenic or osteogenic differentiation lineages. We found that the Sox9 activity level affects the expression of the key transcription factor in adipogenic differentiation, C/EBPβ, and that cyclin D1 mediates the expression of the osteogenic marker osteocalcin in undifferentiated adult bone-marrow-derived rat MSC. Introducing a stable Sox9 knockdown into undifferentiated rat MSC resulted in a marked decrease in proliferation rate and an increase in apoptotic activity. This was linked to a profound upregulation of p21 and cyclin D1 gene and protein expression accompanied by an induction of caspase 3/7 activity and an inhibition of Bcl-2. We observed that Sox9 silencing provoked a delayed S-phase progression and an increased nuclear localization of p21. The protein stability of cyclin D1 was induced in the absence of Sox9 presumably as a function of altered p38 signalling. In addition, the major transcription factor for adipogenic differentiation, C/EBPβ, was repressed after silencing Sox9. The nearly complete absence of C/EBPβ protein as a result of increased destabilization of the C/EBPβ mRNA and the impact on osteocalcin gene expression and protein synthesis, suggests that a delicate balance of Sox9 level is not only imperative for proper chondrogenic differentiation of progenitor cells, but also affects the adipogenic and probably osteogenic differentiation pathways of MSC. Our results identified Sox9 as an important link between differentiation, proliferation and apoptosis in undifferentiated adult rat mesenchymal stem cells, emphasizing the importance of the delicate balance of a precisely regulated Sox9 activity in MSC not only for proper skeletal development during embryogenesis but probably also

  15. Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

    PubMed Central

    Furuta, Miyako; Bridges, Robert S.

    2009-01-01

    The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  17. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions?

    PubMed

    Olivier, B; Chan, J S W; Pattij, T; de Jong, T R; Oosting, R S; Veening, J G; Waldinger, M D

    2006-01-01

    Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes helps to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. These preclinical studies and models contribute to a better understanding of the neurobiology of ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded ejaculation.

  18. Optimization and pharmacological characterization of a refined cisplatin-induced rat model of peripheral neuropathic pain.

    PubMed

    Han, Felicity Yaqin; Wyse, Bruce D; Smith, Maree T

    2014-12-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side-effect of many front-line anticancer drugs. This study was designed to establish and pharmacologically characterize a refined rat model of cisplatin-induced CIPN. Adult male Sprague-Dawley rats received four (n=18) or five (n=18) single intraperitoneal bolus doses of cisplatin at 3 mg/kg, or saline (control group), once-weekly. Body weight and general health were assessed over a 49-day study period. von Frey filaments and the Hargreaves test were used to define the time course for the development of mechanical allodynia and thermal hypoalgesia in the hindpaws and for efficacy assessment of analgesic/adjuvant agents. The general health of rats administered four cisplatin doses was superior to that of rats administered five doses. Mechanical allodynia was fully developed (paw withdrawal thresholds≤6 g) in the bilateral hindpaws from day 32 to 49 for both cisplatin dosing regimens. They also showed significant thermal hypoalgesia in the bilateral hindpaws. In cisplatin-treated rats with paw withdrawal thresholds of up to 6 g, single bolus doses of gabapentin and morphine produced dose-dependent analgesia, whereas meloxicam and amitriptyline lacked efficacy. We have established and pharmacologically characterized a refined rat model of CIPN that is suitable for efficacy profiling of compounds from analgesic discovery programmes.

  19. Noninvasive fatigue fracture model of the rat ulna.

    PubMed

    Tami, A E; Nasser, P; Schaffler, M B; Knothe Tate, M L

    2003-11-01

    Fatigue damage occurs in response to repeated cyclic loading and has been observed in situ in cortical bone of humans and other animals. When microcracks accumulate and coalesce, failure ensues and is referred to as fatigue fracture. Experimental study of fatigue fracture healing is inherently difficult due to the lack of noninvasive models. In this study, we hypothesized that repeated cyclic loading of the rat ulna results in a fatigue fracture. The aim of the study was to develop a noninvasive long bone fatigue fracture model that induces failure through accumulation and coalescence of microdamage and replicates the morphology of a clinical fracture. Using modified end-load bending, right ulnae of adult Sprague-Dawley rats were cyclically loaded in vivo to fatigue failure based on increased bone compliance, which reflects changes in bone stiffness due to microdamage. Preterminal tracer studies with 0.8% Procion Red solution were conducted according to protocols described previously to evaluate perfusion of the vasculature as well as the lacunocanalicular system at different time points during healing. Eighteen of the 20 animals loaded sustained a fatigue fracture of the medial ulna, i.e. through the compressive cortex. In all cases, the fracture was closed and non-displaced. No disruption to the periosteum or intramedullary vasculature was observed. The loading regime did not produce soft tissue trauma; in addition, no haematoma was observed in association with application of load. Healing proceeded via proliferative woven bone formation, followed by consolidation within 42 days postfracture. In sum, a noninvasive long bone fatigue fracture model was developed that lends itself for the study of internal remodeling of periosteal woven bone during fracture healing and has obvious applications for the study of fatigue fracture etiology.

  20. Auto-catalytic Ceria Nanoparticles Offer Neuroprotection to Adult Rat Spinal Cord Neurons

    PubMed Central

    Das, Mainak; Patil, Swanand; Bhargava, Neelima; Kang, Jung-Fong; Riedel, Lisa M.; Seal, Sudipta; Hickman, James J.

    2007-01-01

    This paper describes the evaluation of the auto-catalytic anti-oxidant behavior and biocompatibility of Cerium oxide nanoparticles for applications in spinal cord repair and other diseases of the CNS. The application of a single dose of nano-Ceria at a nano-molar concentration is biocompatible, regenerative and provides a significant neuroprotective effect on adult rat spinal cord neurons. Retention of neuronal function is demonstrated from electrophysiological recordings and the possibility of its application to prevent ischemic insult is suggested from an oxidative injury assay. A mechanism is proposed to explain the auto-catalytic properties of these nanoparticles. PMID:17222903

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

    PubMed

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

    2012-06-01

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

  2. ENU mutagenesis to generate genetically modified rat models.

    PubMed

    van Boxtel, Ruben; Gould, Michael N; Cuppen, Edwin; Smits, Bart M G

    2010-01-01

    The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach for generating genetically modified rats has been the target-selected N-ethyl-N-nitrosourea (ENU) mutagenesis-based technology. Here, we describe the detailed protocols for ENU mutagenesis and mutant retrieval in the rat model organism.

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

    PubMed

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

    2014-04-01

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

  4. The cortical response to sensory deprivation in adult rats is affected by gonadectomy.

    PubMed

    Mowery, Todd M; Elliott, Kevin S; Garraghty, Preston E

    2009-05-01

    The present study investigated the effects of adult-onset sensory deprivation and gonadectomy. Adult male and female rats underwent unilateral transection of the infraorbital nerve. Half of the subjects had been gonadectomized 1 week prior to the nerve injury. We found that the areas of deprived barrels were significantly reduced when compared to barrels in the contralateral control hemisphere, and that this shrinkage was independent of sex and gonadectomy. We also found significant reductions in cytochrome oxidase staining intensity in the deprived barrels. While there were no differences in the magnitude of this effect between males and females, this effect was substantially more pronounced in the gonadectomized subjects. That is, gonadal hormones appeared to play a significant neuroprotective role in the metabolic response of the barrel cortex to deprivation. Thus, either males and females have a common neuroprotective hormonal pathway, or each has a sex-specific hormone pathway that serves an equivalent neuroprotective function.

  5. Natural variation in maternal care shapes adult social behavior in rats.

    PubMed

    Starr-Phillips, Emily J; Beery, Annaliese K

    2014-07-01

    Features of the early postnatal environment profoundly shape later physical and behavioral phenotypes. The amount of licking/grooming that rat dams direct towards their offspring has durable consequences, including behavioral and physiological dimensions of stress reactivity, cognition, and reproductive behavior. We examined how natural variation in maternal care alters social behavior in adult offspring and how this relates to anxiety behavior and oxytocin receptor density. Male and female offspring of mothers who received high levels of licking spent significantly more time in social contact with unfamiliar individuals than did offspring whose dams provided less grooming. Reduced anxiety behavior was associated with greater social interaction. No differences in oxytocin receptor binding assessed by (125) I-OVTA autoradiography were detected between groups. The present investigation characterizes a novel impact of maternal care on adult social interaction behavior, replicates anxiety behavior differences, and illustrates connections between social behavior and anxiety in adulthood across maternal treatment groups.

  6. Eszopiclone and fluoxetine enhance the survival of newborn neurons in the adult rat hippocampus.

    PubMed

    Su, Xiaowei W; Li, Xiao-Yuan; Banasr, Mounira; Duman, Ronald S

    2009-11-01

    Clinical research has shown that co-administration of eszopiclone, a sedative-hypnotic sleeping agent, and fluoxetine, a serotonin uptake inhibitor, exerts an additive antidepressant action in treating patients with both depression and insomnia. Preclinical studies demonstrate that the behavioural actions of antidepressants are linked to neurogenesis in the adult hippocampus. To test the hypothesis that the additive effects of eszopiclone and fluoxetine could act via such a mechanism, the influence of combined administration of these agents on the proliferation and survival of bromodeoxyuridine (BrdU)-labelled newborn cells in the hippocampus of adult rats was determined. Chronic eszopiclone+fluoxetine co-administration significantly increased the survival, but not proliferation, of newborn neurons in dorsal hippocampus by approximately 50%, an effect greater than either drug alone. These findings are consistent with the hypothesis that eszopiclone enhances the antidepressant action of fluoxetine, in part via a novel mechanism that increases the survival of newborn neurons.

  7. Prenatal exposure to SKF-38393 alters the response to light of adult rats.

    PubMed

    Ferguson, S A; Kennaway, D J

    2000-05-15

    The current study examined the consequences of prenatal SKF-38393 exposure on the cellular response in the adult suprachiasmatic nuclei to light. Pregnant rats were injected with the dopamine agonist SKF-38393 or vehicle daily from gestational day 15 to 21. Adult offspring received a light pulse (1 min/2 lux) 4 or 8 h after lights off (ZT16 or ZT20 where ZT=zeitgeber time). Brains were processed for c-FOS-like immunoreactivity in the SCN. At ZT20 the number of cells expressing c-FOS protein after a light pulse was the same in both groups. At ZT16 the number of cells in the SCN of SKF-38393-exposed animals was 58% lower than the vehicle-treated group. The data suggest that prenatal SKF-38393 treatment may have long-term consequences for SCN function.

  8. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    PubMed

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  9. N-Methyl-D-Aspartate Receptor-Mediated Axonal Injury in Adult Rat Corpus Callosum

    PubMed Central

    Zhang, Jingdong; Liu, Jianuo; Fox, Howard S.; Xiong, Huangui

    2013-01-01

    Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N-methyl-D-aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input–output response. Both Glut and NMDA decreased the CAP amplitude and input–output responses, suggesting an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement of NMDAR in Glut-induced axonal injury was further assayed by detection of β-amyloid precursor protein (β-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β-APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro. PMID:23161705

  10. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    PubMed

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  11. Structural changes in the adult rat auditory system induced by brief postnatal noise exposure.

    PubMed

    Ouda, Ladislav; Burianová, Jana; Balogová, Zuzana; Lu, Hui Pin; Syka, Josef

    2016-01-01

    In previous studies (Grécová et al., Eur J Neurosci 29:1921-1930, 2009; Bures et al., Eur J Neurosci 32:155-164, 2010), we demonstrated that after an early postnatal short noise exposure (8 min 125 dB, day 14) changes in the frequency tuning curves as well as changes in the coding of sound intensity are present in the inferior colliculus (IC) of adult rats. In this study, we analyze on the basis of the Golgi-Cox method the morphology of neurons in the IC, the medial geniculate body (MGB) and the auditory cortex (AC) of 3-month-old Long-Evans rats exposed to identical noise at postnatal day 14 and compare the results to littermate controls. In rats exposed to noise as pups, the mean total length of the neuronal tree was found to be larger in the external cortex and the central nucleus of the IC and in the ventral division of the MGB. In addition, the numerical density of dendritic spines was decreased on the branches of neurons in the ventral division of the MGB in noise-exposed animals. In the AC, the mean total length of the apical dendritic segments of pyramidal neurons was significantly shorter in noise-exposed rats, however, only slight differences with respect to controls were observed in the length of basal dendrites of pyramidal cells as well as in the neuronal trees of AC non-pyramidal neurons. The numerical density of dendritic spines on the branches of pyramidal AC neurons was lower in exposed rats than in controls. These findings demonstrate that early postnatal short noise exposure can induce permanent changes in the development of neurons in the central auditory system, which apparently represent morphological correlates of functional plasticity.

  12. Neonatal stress alters LTP in freely moving male and female adult rats.

    PubMed

    Kehoe, P; Bronzino, J D

    1999-01-01

    We previously reported that neonatal isolation stress significantly changes measures of hippocampal long-term potentiation (LTP) in male and female juvenile rats, i.e., at 30 days of age. The changes in dentate granule population measures, i.e., excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway, indicated that juvenile rats exposed to neonatal isolation exhibit different enhancement profiles with respect to both the magnitude and duration of LTP in a sex-specific manner. Isolated males showed a significantly greater enhancement of LTP, while female "isolates" showed significantly longer LTP duration when compared to all other groups. The present study was designed to determine whether the effects of the neonatal isolation stress paradigm endures into adulthood. Rats isolated from their mothers for 1 h per day during postnatal days 2-9 were surgically prepared at 70-90 days of age, with stimulating and recording electrodes placed in the medial perforant pathway and the hippocampal dentate gyrus, respectively. Prior to tetanization, no significant effect of sex or treatment was obtained for baseline measures of EPSP slope or PSA. In order to rule out baseline differences in hippocampal cell excitability in female adult rats, we measured the response of dentate granule cells for one estrus cycle and found no pretetanization enhancement in the evoked response in either controls or previously stressed rats. Following tetanization, there was a significant treatment and sex effect. During the induction of LTP, PSA values were significantly enhanced in both isolated males and females and had significantly longer LTP duration when compared to the unhandled control group. Additionally, we observed that females took longer to reach baseline levels than males. Taken together, these results indicate that repeated infant isolation stress enhances LTP induction and duration in both males and

  13. Sustained increase in adult neurogenesis in the rat hippocampal dentate gyrus after transient brain ischemia.

    PubMed

    Wang, Congmin; Zhang, Mingguang; Sun, Chifei; Cai, Yuqun; You, Yan; Huang, Liping; Liu, Fang

    2011-01-13

    It is known that the number of newly generated neurons is increased in the young and adult rodent subventricular zone (SVZ) and dentate gyrus (DG) after transient brain ischemia. However, it remains unclear whether increase in neurogenesis in the adult DG induced by ischemic stroke is transient or sustained. We here reported that from 2 weeks to 6 months after transient middle cerebral artery occlusion (MCAO), there were more doublecortin positive (DCX+) cells in the ipsilateral compared to the sham-control and contralateral DG of the adult rat. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected 2 days after MCAO to label newly generated cells, a large number of BrdU-labeled neuroblasts differentiated into mature granular neurons. These BrdU-labeled neurons survived for at least 6 months. When BrdU was injected 6 weeks after injury, there were still more newly generated neuroblasts differentiated into mature neurons in the ipsilateral DG. Altogether, our data indicate that transient brain ischemia initiates a prolonged increase in neurogenesis and promotes the normal development of the newly generated neurons in the adult DG.

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

    SciTech Connect

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

    2011-03-01

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

  15. Effect of serotonergic drugs on footshock-induced ultrasonic vocalization in adult male rats.

    PubMed

    Sánchez, C.

    1993-06-01

    Modulation of ultrasonic vocalization (20-30kHz) emitted by adult rats under stressful conditions such as unavoidable foot-shock has been evaluated as a model of anxiety. The effects of 5-HT(1A) receptor agonists with different intrinsic activities and the role of other 5-HT(1) receptor subtypes, and of 5-HT(2) and 5-HT(3) receptors, in mediation of ultrasonic vocalization were studied, as were the effects of increasing serotonergic activity by administration of the 5-HT releaser fenfluramine or the 5-HT precursor 1-5 HTP. The time spent vocalizing 1-6min after four increascapable (1.0mA) footshocks was recorded. Drugs with affinity for 5-HT(1A) receptors (i.e. 8-OHDPAT, flesinoxan, ipsapirone, buspirone, gepirone, NAN-190) abolished the vocalization irrespective of their efficacy. The mixed 5-HT(1) receptor and beta-adrenoceptor antagonists (-)-alprenolol and pindolol inhibited foot-shock-induced ultrasonic vocalization, whereas (-) penbutolol was ineffective. The beta(1)-adrenoceptor antagonist metoprolol and the beta(2)-adrenoceptor antagonist ICI 118.551 were without effect. This suggests that (-)-alprenolol and pindolol act as partial 5-HT(1) agonists in the test model. The non-selective 5-HT(1) receptor agonists eltoprazine, m-CPP and 5-MeODMT and the 5-HT(2) receptor agonists DO1 and d-LSD also abolished the vocalization, whereas the 5-HT(2) receptor antagonist ritanserin and the 5-HT(3) receptor antagonists ondansetron, ICS 205-930 and zacopride were without effect. (-)-Penbutolol reversed 8-OHDPAT-induced inhibition. Ritanserin reversed DOI-induced inhibition of ultrasonic vocalization, but not 8-OHDPAT-induced inhibition. This suggests that there is no functional interaction between 5-HT(1A) and 5-HT(2) receptors in this model. Fenfluramine and 1-5-HTP dose-dependently inhibited footshock-induced ultrasonic vocalization. These findings indicate that the effect most likely is mediated by postsynaptic 5-HT receptors, although contribution by presynaptic 5

  16. Modeling interpopulation dispersal by banner-tailed kangaroo rats

    USGS Publications Warehouse

    Skvarla, J.L.; Nichols, J.D.; Hines, J.E.; Waser, P.M.

    2004-01-01

    Many metapopulation models assume rules of population connectivity that are implicitly based on what we know about within-population dispersal, but especially for vertebrates, few data exist to assess whether interpopulation dispersal is just within-population dispersal "scaled up." We extended existing multi-stratum mark-release-recapture models to incorporate the robust design, allowing us to compare patterns of within- and between-population movement in the banner-tailed kangaroo rat (Dipodomys spectabilis). Movement was rare among eight populations separated by only a few hundred meters: seven years of twice-annual sampling captured >1200 individuals but only 26 interpopulation dispersers. We developed a program that implemented models with parameters for capture, survival, and interpopulation movement probability and that evaluated competing hypotheses in a model selection framework. We evaluated variants of the island, stepping-stone, and isolation-by-distance models of interpopulation movement, incorporating effects of age, season, and habitat (short or tall grass). For both sexes, QAICc values clearly favored isolation-by-distance models, or models combining the effects of isolation by distance and habitat. Models with probability of dispersal expressed as linear-logistic functions of distance and as negative exponentials of distance fit the data equally well. Interpopulation movement probabilities were similar among sexes (perhaps slightly biased toward females), greater for juveniles than adults (especially for females), and greater before than during the breeding season (especially for females). These patterns resemble those previously described for within-population dispersal in this species, which we interpret as indicating that the same processes initiate both within- and between-population dispersal.

  17. Does Pilocarpine-Induced Epilepsy in Adult Rats Require Status epilepticus?

    PubMed Central

    Navarro Mora, Graciela; Bramanti, Placido; Osculati, Francesco; Chakir, Asmaa; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea; Fabene, Paolo Francesco

    2009-01-01

    Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE) is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a) whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS) and b) whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22) months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy. PMID:19503612

  18. Examining a Model of Life Satisfaction among Unemployed Adults

    ERIC Educational Resources Information Center

    Duffy, Ryan D.; Bott, Elizabeth M.; Allan, Blake A.; Torrey, Carrie L.

    2013-01-01

    The present study examined a model of life satisfaction among a diverse sample of 184 adults who had been unemployed for an average of 10.60 months. Using the Lent (2004) model of life satisfaction as a framework, a model was tested with 5 hypothesized predictor variables: optimism, job search self-efficacy, job search support, job search…

  19. Evidence for a General Factor Model of ADHD in Adults

    ERIC Educational Resources Information Center

    Gibbins, Christopher; Toplak, Maggie E.; Flora, David B.; Weiss, Margaret D.; Tannock, Rosemary

    2012-01-01

    Objective: To examine factor structures of "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.) symptoms of ADHD in adults. Method: Two sets of models were tested: (a) models with inattention and hyperactivity/impulsivity as separate but correlated latent constructs and (b) hierarchical general factor models with a general factor for…

  20. Establishment of rat model of central venous catheter (CVC): associated infection and evaluation of the virulence of bacterial biofilms.

    PubMed

    Ye, Lian-Hua; Huang, Yun-Chao; Guo, Feng-Li; Liu, Xin; Zhao, Guang-Qiang; Duan, Lin-Can; Jin, Cong-Guo

    2014-09-01

    In this study, a central venous catheter (CVC)-associated infection model was established in rats to investigate and evaluate the effect of biofilms on the virulence of the pathogens. Twenty-four adult SD rats were randomly divided into biofilm positive (BF+) and biofilm negative (BF-) groups to be challenged with strains of S.epidermidis. Serum levels of inflammatory cytokines were measured and the infection rate and counts of bacteria cells were studied. Compared to rats of BF- group, the serum level of TNF and IL-6 significantly increased in rats of BF+ group (P < 0.01) and the level of IL-10 and IFN-γ significantly decreased (P < 0.01), striking the balance of pro-inflammatory/anti-inflammatory cytokines. The infection rate and bacterial counts in tissues and blood of rats of BF + group were significantly higher than those of rats of BF- group (P < 0.05).Inflammatory cell infiltration in vital organs (heart, lung, liver and kidneys) was more significant in rats of BF+ group than that of rats of BF- group. CVC-associated infection model can be successfully reproduced in rats by injecting 5 × 10(6) CFU of S.epidermidis. Biofilm formation can significantly enhance the virulence of the bacteria, leading to uncontrolled infection. The serum level of inflammatory cytokines, infection rate and the extent of inflammatory cell infiltration are important markers for evaluating the virulence of biofilm.

  1. Inhibition by dietary D-psicose of body fat accumulation in adult rats fed a high-sucrose diet.

    PubMed

    Ochiai, Masaru; Nakanishi, Yosuke; Yamada, Takako; Iida, Tetsuo; Matsuo, Tatsuhiro

    2013-01-01

    We investigated the anti-obesity effects of dietary D-psicose on adult rats fed a high-sucrose diet. Wistar rats (16 weeks old) that had previously been fed a high-sucrose diet (HSD) were fed HSD or a high-starch diet (HTD) with or without 5% D-psicose for 8 weeks. The food efficiency, carcass fat percentage, abdominal fat accumulation, and body weight gain were all significantly suppressed by dietary D-psicose.

  2. DOPAMINE RECEPTOR INACTIVATION IN THE CAUDATE-PUTAMEN DIFFERENTIALLY AFFECTS THE BEHAVIOR OF PREWEANLING AND ADULT RATS

    PubMed Central

    DER-GHAZARIAN, T.; GUTIERREZ, A.; VARELA, F. A.; HERBERT, M. S.; AMODEO, L. R.; CHARNTIKOV, S.; CRAWFORD, C. A.; MCDOUGALL, S. A.

    2012-01-01

    The irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been used to study the ontogeny of dopamine (DA) receptor functioning in the young and adult rat. Most notably, systemic administration of EEDQ blocks the DA agonist-induced behaviors of adult rats, while leaving the behavior of preweanling rats unaffected. The purpose of the present study was to: (a) determine whether the age-dependent actions of EEDQ involve receptors located in the dorsal caudate-putamen (CPu) and (b) confirm that EEDQ's behavioral effects result from the inactivation of DA receptors rather than some other receptor type. In Experiment 1, EEDQ or DMSO were bilaterally infused into the CPu on PD 17 or PD 84. After 24 h, rats were given bilateral microinjections of the full DA agonist R(–)-propylnorapomorphine (NPA) or vehicle into the dorsal CPu and behavior was assessed for 40 min. In Experiment 2, preweanling rats were treated as just described, except that DA receptors were protected from EEDQ-induced alkylation by administering systemic injections of D1 (SCH23390) and D2 (sulpiride) receptor antagonists. As predicted, microinjecting EEDQ into the dorsal CPu attenuated the NPA-induced locomotor activity and stereotypy of adult rats. In contrast, rats given bilateral EEDQ infusions on PD 17 exhibited a potentiated locomotor response when treated with NPA. Experiment 2 showed that DA receptor inactivation was responsible for NPA's actions. A likely explanation for these results is that EEDQ inactivates a sizable percentage of DA receptors on PD 17, but leaves the remaining receptors in a supersensitive state. This receptor supersensitivity, which probably involves alterations in G protein coupling, could account for NPA-induced locomotor potentiation. Either adult rats do not show a similar EEDQ-induced change in receptor dynamics or DA receptor inactivation was more complete in older animals and effectively eliminated the expression of DA agonist

  3. Neonatal isolation decreases cued fear conditioning and frontal cortical histone 3 lysine 9 methylation in adult female rats.

    PubMed

    Kao, Gour-Shenq; Cheng, Ling-Yi; Chen, Li-Hsien; Tzeng, Wen-Yu; Cherng, Chienfang G; Su, Chien-Chou; Wang, Ching-Yi; Yu, Lung

    2012-12-15

    Early life stress is thought to enhance adult susceptibility to stress and stress-related mood disorders. In this study, fear-potentiated startle was used to model the acquisition of a traumatic event-related memory in female rats experiencing early life stress. Daily 1-hr maternal and sibling separation throughout day 2-9 postpartum (D2-9 PP) caused a decrease in the fear-potentiated startle, but not acoustic startle baseline, in adult female rats. The separation procedure did not affect corticosterone secretion but produced an increase in serum estradiol concentration. Moreover, the separation procedure did not affect histone 3 lysine 9 (H3K9) acetylation but decreased H3K9 mono- and tri-methylation in frontal cortices. Treatment with 5-aza-2'-deoxycytidine (AZA) (5mg/kg at alternative days from D2PP to D9PP or 10mg/kg at D5PP and D9PP), a DNA methylation inhibitor, did not affect the separation-decreased fear-potentiated startle. Treatment with valproic acid (VPA), a histone deacetylase inhibitor, at 3 dosing regimens (300mg/kg at D2-9PP; 100mg/kg at D2-4PP, 200mg/kg at D5-7PP, 300mg/kg at D8-9PP; 100mg/kg at D2-5PP, 200mg/kg at D6-9PP) prior to daily separation reversed such a decrease in fear-potentiated startle. The lowest effective VPA dosing regimen used (100mg/kg at D2-5PP, 200mg/kg at D6-9PP) reversed the separation-decreased H3K9 mono- and tri-methylation in frontal cortices. Eight-day VPA (300mg/kg/day) and AZA (5mg/kg/day) administrations starting at D28PP were ineffective in altering the separation-decreased fear-potentiated startle. We, hereby, suggest that decreased frontal cortical H3K9 mono- and tri-methylation may be involved in early life separation-decreased fear memory of adult rats.

  4. Subchronic treatment with phencyclidine in adolescence leads to impaired exploratory behavior in adult rats without altering social interaction or N-methyl-D-aspartate receptor binding levels.

    PubMed

    Metaxas, A; Willems, R; Kooijman, E J M; Renjaän, V A; Klein, P J; Windhorst, A D; Donck, L Ver; Leysen, J E; Berckel, B N M van

    2014-11-01

    Although both the onset of schizophrenia and human phencyclidine (PCP) abuse typically present within the interval from adolescence to early adulthood, the majority of preclinical research employing the PCP model of schizophrenia has been conducted on neonatal or adult animals. The present study was designed to evaluate the behavioral and neurochemical sequelae of subchronic exposure to PCP in adolescence. Male 35-42-day-old Sprague Dawley rats were subcutaneously administered either saline (10 ml · kg(-1) ) or PCP hydrochloride (10 mg · kg(-1) ) once daily for a period of 14 days (n = 6/group). The animals were allowed to withdraw from treatment for 2 weeks, and their social and exploratory behaviors were subsequently assessed in adulthood by using the social interaction test. To examine the effects of adolescent PCP administration on the regulation of N-methyl-D-aspartate receptors (NMDARs), quantitative autoradiography was performed on brain sections of adult, control and PCP-withdrawn rats by using 20 nM (3) H-MK-801. Prior subchronic exposure to PCP in adolescence had no enduring effects on the reciprocal contact and noncontact social behavior of adult rats. Spontaneous rearing in response to the novel testing arena and time spent investigating its walls and floor were reduced in PCP-withdrawn animals compared with control. The long-term behavioral effects of PCP occurred in the absence of persistent deficits in spontaneous locomotion or self-grooming activity and were not mediated by altered NMDAR density. Our results document differential effects of adolescent PCP administration on the social and exploratory behaviors of adult rats, suggesting that distinct neurobiological mechanisms are involved in mediating these behaviors.

  5. Neonatal nicotine exposure increases excitatory synaptic transmission and attenuates nicotine-stimulated GABA release in the adult rat hippocampus.

    PubMed

    Damborsky, Joanne C; Griffith, William H; Winzer-Serhan, Ursula H

    2015-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1-7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking.

  6. Characterization of strychnine-sensitive glycine receptors in acutely isolated adult rat basolateral amygdala neurons.

    PubMed

    McCool, B A; Botting, S K

    2000-03-24

    Large concentrations of the beta-amino acid, taurine, can be found in many forebrain areas such as the basolateral amygdala, a portion of the limbic forebrain intimately associated with the regulation of fear/anxiety-like behaviors. In addition to its cytoprotective and osmoregulatory roles, taurine may also serve as an agonist at GABA(A)- and strychnine-sensitive glycine receptors. In this latter context, the present study demonstrates that application of taurine to acutely isolated neurons from the basolateral amygdala of adult rats causes significant alterations in resting membrane current, as measured by whole-cell patch clamp electrophysiology. Using standard pharmacological approaches, we find that currents gated by concentrations of taurine adult rats.

  7. Exposure to constant light during testis development increases daily sperm production in adult Wistar rats.

    PubMed

    Rocha, D C; Debeljuk, L; França, L R

    1999-06-01

    Testis histometry and daily sperm production (DSP) were evaluated in adult (160-day-old) Wistar rats exposed to constant light for the first 25 days after birth, and compared with control animals which were exposed to a 12 h-light-12 h-dark light regimen. Significantly greater (P < 0.05) numbers of Sertoli cell nucleoli and round spermatids per cross-section of seminiferous tubule were found in animals exposed to constant light. In addition, epididymis weight, DSP per testis and per gram of testis, as well as Leydig cell compartment volume, were significantly increased in treated animals. Although there was a clear trend toward an increased Sertoli cell population per testis in animals exposed to constant light, this difference was not statistically significant (P < 0.05). The number of round spermatids as expressed per Sertoli cell was the same in both groups. Surprisingly, the diameter and volume of round spermatid nucleus at stages I and VII of the cycle of seminiferous epithelium were significantly lower (P < 0.05) in treated animals. In conclusion, constant illumination during neonatal testis development increased sperm production and Leydig cell compartment volume in adult rats probably through a mechanism involving elevated follicle stimulating hormone and luteinizing hormone during the prepubertal period. To our knowledge, this is the first study showing that altering the light regimen can affect sperm production in non-seasonal breeders.

  8. Diazepam affects the nuclear thyroid hormone receptor density and their expression levels in adult rat brain.

    PubMed

    Constantinou, Caterina; Bolaris, Stamatis; Valcana, Theony; Margarity, Marigoula

    2005-07-01

    Thyroid hormones (THs) are involved in the occurrence of anxiety and affective disorders; however, the effects following an anxiolytic benzodiazepine treatment, such as diazepam administration, on the mechanism of action of thyroid hormones has not yet been investigated. The effect of diazepam on the in vitro nuclear T3 binding, on the relative expression of the TH receptors (TRs) and on the synaptosomal TH availability were examined in adult rat cerebral hemispheres 24 h after a single intraperitoneal dose (5 mg/kg BW) of this tranquillizer. Although, diazepam did not affect the availability of TH either in blood circulation or in the synaptosomal fraction, it decreased (33%) the nuclear T3 maximal binding density (B(max)). No differences were observed in the equilibrium dissociation constant (K(d)). The TRalpha2 variant (non-T3-binding) mRNA levels were increased by 33%, whereas no changes in the relative expression of the T3-binding isoforms of TRs (TRalpha1, TRbeta1) were observed. This study shows that a single intraperitoneal injection of diazepam affects within 24 h, the density of the nuclear TRs and their expression pattern. The latest effect occurs in an isoform-specific manner involving specifically the TRalpha2 mRNA levels in adult rat brain.

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

    PubMed

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

    2008-05-01

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

  10. Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2016-04-21

    Methylphenidate (MPH) is a central stimulant, prescribed for the treatment of attention deficit/hyperactivity disorder. The long-term behavioral consequences of MPH treatment are unknown. In this study, the oxidative stress and neuroinflammation induced by various doses of MPH were investigated. Forty adult male rats were divided into 5 groups; and treated with different doses of MPH for 21 days. Twenty four hours after drug treatment, Open Field Test (OFT) was performed in all animals. At the end of the study, blood cortisol level (BCL) was measured and hippocampus was isolated and oxidative stress and inflammation parameters and histological changes were analyzed. Chronic MPH at all doses decreased central square entries, number of rearing, ambulation distance and time spent in central square in OFT. BCL increased in doses 10 and 20mg/kg of MPH. Furthermore, MPH in all doses markedly increased lipid peroxidation, mitochondrial oxidized glutathione (GSSG) level, Interleukin 1β (IL-1β) and Tumor Necrosis Factor α (TNF-α) in isolated hippocampus. MPH (10 and 20mg/kg) treated groups had decreased mitochondrial reduced glutathione (GSH) content, and reduced superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) activities. 10 and 20mg/kg of MPH change cell density and morphology of cells in Dentate Gyrus (DG) and CA1 areas of hippocampus. Chronic treatment with high doses of MPH can cause oxidative stress, neuroinflammation and neurodegeneration in hippocampus of adult rats.

  11. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat.

    PubMed

    Wang, Hui-Dong; Dunnavant, Floyd D; Jarman, Tabitha; Deutch, Ariel Y

    2004-07-01

    The generation of new cells in the adult mammalian brain may significantly modify pathophysiological processes in neuropsychiatric disorders. We examined the ability of chronic treatment with the antipsychotic drugs (APDs) olanzapine and haloperidol to increase the number and survival of newly generated cells in the prefrontal cortex (PFC) and striatal complex of adult male rats. Animals were treated with olanzapine or haloperidol for 3 weeks and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. Half of the animals continued on the same APD for two more weeks after BrdU challenge, with the other half receiving vehicle during this period. Olanzapine but not haloperidol significantly increased both the total number and density of BrdU-labeled cells in the PFC and dorsal striatum; no effect was observed in the nucleus accumbens. Continued olanzapine treatment after the BrdU challenge did not increase the survival of newly generated cells. The newly generated cells in the PFC did not express the neuronal marker NeuN. Despite the significant increase in newly generated cells in the PFC of olanzapine-treated rats, the total number of these cells is low, suggesting that the therapeutic effects of atypical APD treatment may not be due to the presence of newly generated cells that have migrated to the cortex.

  12. Bisphenol A exposure at an environmentally relevant dose induces meiotic abnormalities in adult male rats.

    PubMed

    Liu, Chuan; Duan, Weixia; Zhang, Lei; Xu, Shangcheng; Li, Renyan; Chen, Chunhai; He, Mindi; Lu, Yonghui; Wu, Hongjuan; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    Whether environmental exposure to bisphenol A (BPA) may induce reproductive disorders is still controversial but certain studies have reported that BPA may cause meiotic abnormalities in C. elegans and female mice. However, little is known about the effect of BPA on meiosis in adult males. To determine whether BPA exposure at an environmentally relevant dose could induce meiotic abnormalities in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 20 μg/kg body weight (bw)/day for 60 consecutive days. We found that BPA significantly increased the proportion of stage VII seminiferous epithelium and decreased the proportion of stage VIII. Consequently, spermiation was inhibited and spermatogenesis was disrupted. Further investigation revealed that BPA exposure delayed meiosis initiation in the early meiotic stage and induced the accumulation of chromosomal abnormalities and meiotic DNA double-strand breaks (DSBs) in the late meiotic stage. The latter event subsequently activated the phosphatidylinositol 3-kinase-related protein kinase (ATM). Our results suggest that long-term exposure to BPA may lead to continuous meiotic abnormalities and ultimately put mammalian reproductive health at risk.

  13. Maternal separation exaggerates spontaneous recovery of extinguished contextual fear in adult female rats.

    PubMed

    Xiong, Gui-Jing; Yang, Yuan; Wang, Li-Ping; Xu, Lin; Mao, Rong-Rong

    2014-08-01

    Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD.

  14. Sex mediates dopamine and adrenergic receptor expression in adult rats exposed prenatally to cocaine

    PubMed Central

    Ferris, Mark J.; Mactutus, Charles F.; Silvers, Janelle M.; Hasselrot, Ulla; Strupp, Barbara J.; Booze, Rosemarie M.

    2010-01-01

    The extent of catecholaminergic receptor and respective behavioral alterations associated with prenatal cocaine exposure varies according to exogenous factors such as the amount, frequency, and route of maternal exposure, as well as endogenous factors such as specific brain regions under consideration and sex of the species. The goal of the current study was to use autoradiography to delineate possible moderators of dopaminergic and adrenergic receptor expression in adult rat offspring exposed to cocaine in utero. The current study demonstrated sex-dependent D1 receptor, α2, and noradrenergic transporter binding alterations in prelimbic, hippocampus, and anterior cingulate regions of adult rat brains exposed to cocaine during gestational days 8–21. Of further interest was the lack of alterations in the nucleus accumbens for nearly all receptors/transporters investigated, as well as the lack of alterations in D3 receptor binding in nearly all of the regions investigated (nucleus accumbens, prelimbic region, hippocampus, and cingulate gyrus). Thus, the current investigation demonstrated persistent receptor and transporter alterations that extend well into adulthood as a result of cocaine exposure in utero. Furthermore, the demonstration that sex played a mediating role in prenatal cocaine-induced, aberrant receptor/transporter expression is of primary importance for future studies that seek to control for sex in either design or analysis. PMID:17933484

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

    NASA Astrophysics Data System (ADS)

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

    2008-08-01

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

  16. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

    PubMed

    Greisen, Mia H; Altar, C Anthony; Bolwig, Tom G; Whitehead, Richard; Wörtwein, Gitta

    2005-03-15

    Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

  17. Children's and Adults' Models for Predicting Teleological Action: The Development of a Biology-Based Model.

    ERIC Educational Resources Information Center

    Opfer, John E.; Gelman, Susan A.

    2001-01-01

    Two studies examined models that preschoolers, fifth-graders, and adults use to guide predictions of self-beneficial, goal-directed action. Found that preschoolers' predictions were consistent with an animal-based model, fifth-graders' with biology-based and complexity-based models, and adults' predictions with a biology-based model. All age…

  18. IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats

    PubMed Central

    Pang, Yi; Bhatt, Abhay J.; Fan, Lir-Wan

    2015-01-01

    We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an antiinflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist. PMID:25665855

  19. IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats.

    PubMed

    Lan, Kuo-Mao; Tien, Lu-Tai; Pang, Yi; Bhatt, Abhay J; Fan, Lir-Wan

    2015-04-02

    We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist.

  20. Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model.

    PubMed

    Yang, Xiaoxia; Doerge, Daniel R; Fisher, Jeffrey W

    2013-07-01

    Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies on the maturation of phase II enzymes coupled with serum time course data in pups. The calibrated model predicted the measured serum concentrations of BPA and BPA conjugates after administration of 100μg/kg of d6-BPA in adult rats (oral gavage and intravenous administration) and postnatal days 3, 10, and 21 pups (oral gavage). The observed age-dependent BPA serum concentrations were partially attributed to the immature metabolic capacity of pups. A comparison of the dosimetry of BPA across immature rats and monkeys suggests that dose adjustments would be necessary to extrapolate toxicity studies from neonatal rats to infant humans.

  1. Rat model of cholelithiasis with human gallstones implanted in cholestasis-induced virtual gallbladder

    PubMed Central

    Cona, Marlein Miranda; Liu, Yewei; Yin, Ting; Feng, Yuanbo; Chen, Feng; Mulier, Stefaan; Li, Yue; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2016-01-01

    AIM: To facilitate translational research on cholelithiasis, we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species. METHODS: Under anesthesia, 16 adult rats of equal genders underwent two times of abdominal surgery. First, their common bile duct (CBD) was ligated to cause cholestasis by total biliary obstruction (TBO). On day 0, 1, 3, 7, 14, 21 and 28 after TBO, magnetic resonance imaging (MRI) was conducted to monitor the dilatation of the CBD, and blood was sampled to analyze total serum bilirubin (TSB). Secondly, on day 30, the abdomen was re-opened and gallstone(s) collected from human patients were implanted in the dilated CBD as a virtual gallbladder (VGB), which was closed by suture ligation. This rat cholelithiasis model was examined by MRI, clinical observation, microcholangiography and histology. RESULTS: All rats survived two laparotomies. After ligation, the CBD was dilated to a stable size of 4 to 30 mm in diameter on day 21-28, which became a VGB. The rats initially showed signs of jaundice that diminished over time, which paralleled with the evolving TSB levels from 0.6 ± 0.3 mg/dL before ligation, through a peak of 10.9 ± 1.9 mg/dL on day 14, until a nearly normalized value after day 28. The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter. The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology. CONCLUSION: A rat model cholelithiasis with human gallstones has been established, which proves feasible, safe, reliable, nontoxic and cost-effective. Given the gallstones of human origin, applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration. PMID:27376020

  2. Comparison of DEXA and QMR for assessing fat and lean body mass in adult rats.

    PubMed

    Miller, Colette N; Kauffman, Tricia G; Cooney, Paula T; Ramseur, Keshia R; Brown, Lynda M

    2011-04-18

    There are several techniques used to measure body composition in experimental models including dual energy X-ray absorptiometry (DEXA) and quantitative magnetic resonance (QMR). DEXA/QMR data have been compared in mice, but have not been compared previously in rats. The goal of this study was to compare DEXA and QMR data in rats. We used rats that varied by sex, diet, and age, in addition we compared dissected samples containing subcutaneous (pelt) or visceral fat (carcass). The data means were compared by focusing on the differences between DEXA/QMR data using a series of scatter plots without assuming that either method is more accurate as suggested by Bland and Altman. DEXA/QMR data did not agree sufficiently in carcass or pelt FM or in pelt LBM. The variation observed within these groups suggests that DEXA and QMR measurements are not comparable. Carcass LBM in young rats did yield comparable data once the data for middle-aged rats was removed. The variation in our data may be a result of different direct and indirect measures that DEXA and QMR technologies use to quantify FM and LBM. DEXA measures FM and estimates fat-free mass. In contrast, QMR uses separate equations of magnetic resonance to measure FM, LBM, total body water and free water. We found that QMR overestimated body mass in our middle-aged rats, and this increased the variation between methods. Our goal was to evaluate the precision of DEXA/QMR data in rats to determine if they agree sufficiently to allow direct comparison of data between methods. However DEXA and QMR did not yield the same estimates of FM or LBM for the majority of our samples.

  3. Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats.

    PubMed

    Gomes, Karin M; Inácio, Cecília G; Valvassori, Samira S; Réus, Gislaine Z; Boeck, Carina R; Dal-Pizzol, Felipe; Quevedo, João

    2009-11-06

    The prescription of methylphenidate (MPH) has dramatically increased in this decade for attention deficit hyperactivity disorder (ADHD) treatment. The action mechanism of MPH is not completely understood and studies have been demonstrated that MPH can lead to neurochemical adaptations. Superoxide radical anion is not very reactive per se. However, severe species derived from superoxide radical anion mediate most of its toxicity. In this study, the superoxide level in submitochondrial particles was evaluated in response to treatment with MPH in the age-dependent manner in rats. MPH was administrated acutely or chronically at doses of 1, 2 or 10 mg/kg i.p. The results showed that the acute administration of MPH in all doses in young rats increased the production of superoxide in the cerebellum and only in the high dose (10mg/kg) in the hippocampus, while chronic treatment had no effect. However, acute treatment in adult rats had no effect on production of superoxide, but chronic treatment decreased the production of superoxide in the cerebellum at the lower doses. Our data suggest that the MPH treatment can influence on production of superoxide in some brain areas, but this effect depends on age of animals and treatment regime with MPH.

  4. Choline dietary supplementation improves LiCl-induced context aversion retention in adult rats.

    PubMed

    Moreno, Hayarelis C; Gil, Marta; Carias, Diamela; Gallo, Milagros; de Brugada, Isabel

    2012-06-25

    Previous studies have demonstrated that choline is an essential nutrient during prenatal and early postnatal developmental periods. Thus, the availability of choline during these periods produces some beneficial effects on hippocampal-dependent learning and memory in rats. However, research on the effect of adult choline supplementation on learning and memory abilities is scarce. In the present study, 3-4 month-old male Wistar rats receiving a 7-week choline-supplemented diet (4.5 fold that of a standard diet) and control rats receiving a standard diet were trained in a LiCl-induced contextual aversion task. Short and long-term context aversion retention was assessed by recording the consumption of a flavoured solution in the aversive and safe contexts over two subsequent tests. Statistical analysis showed that the supplemented group exhibited greater intake suppression in the aversive context than in the safe context when two retention tests were applied 3 and 15 days after conditioning. These results suggest that increasing dietary choline availability during adulthood may favour the retention of a context aversion.

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

    PubMed

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

    2013-06-01

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

  6. Feeding neonatal rats with IgG antibodies leads to humoral hyporesponsiveness in the adult.

    PubMed Central

    Peppard, J V

    1992-01-01

    Feeding monoclonal IgG2a or IgG1 anti-horseradish peroxidase (HRP) antibodies to 12-16-day-old neonatal rats caused a profound suppression of the humoral anti-HRP response in these rats as adults. The hyporesponsiveness to HRP was specific and long-lasting (up to 5 months). It was shown to be dose dependent, requiring relatively large doses of IgG (100-600 micrograms) for maximum effect. Secondary IgG (IgG1, IgG2a and IgG2b) responses were most depressed. The effect could be reproduced by i.p. injection of antibody. Hyporesponsiveness was not attributable to circulating antiidiotype antibodies directed against the monoclonal IgG, nor to the continued presence of the monoclonal anti-HRP since rats receiving antibody at or some weeks after the time of weaning and gut 'closure' responded well to subsequent HRP challenge. The effect was thus dependent on IgG administered over the identical period during which the neonatal circulation is rich in maternal IgG supplied via the milk. A direct function for maternal IgG in moulding the immune repertoire of the offspring, as well as providing passive protection, is suggested by these results. PMID:1385314

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  8. Cadmium chloride exposure modifies amino acid daily pattern in the mediobasal hypothalamus in adult male rat.

    PubMed

    Caride, A; Fernández-Pérez, B; Cabaleiro, T; Bernárdez, G; Lafuente, A

    2010-01-01

    The present study was conducted to investigate the possible effects of cadmium exposure on the daily pattern of aspartate, glutamate, glutamine, gamma-aminobutyric acid (GABA) and taurine levels in the mediobasal hypothalamus of adult male rats. For this purpose, animals were treated with cadmium at two different exposure doses (25 and 50 mg l(-1) of cadmium chloride, CdCl(2)) in the drinking water for 30 days. Control age-matched rats received CdCl(2)-free water. After the treatment, rats were killed at six different time intervals throughout a 24 h cycle. CdCl(2) exposure modified the amino acid daily pattern, as it decreased aspartate, glutamate, GABA and taurine levels at 12:00 h with both exposure doses employed. In addition, the treatment with 25 mg l(-1) of CdCl(2) induced the appearance of minimal values at 16:00 h and maximal values between 04:00 and 08:00 h for glutamate, and a peak of glutamine content at 20:00 h. The heavy metal also decreased GABA medium levels around the clock in the mediobasal hypothalamus. However, CdCl(2) did not alter the metabolic correlation between glutamate, aspartate, glutamine and GABA observed in control animals. These results suggest that CdCl(2) induced several alterations in aspartate, glutamate, glutamine, GABA and taurine daily pattern in the mediobasal hypothalamus and those changes may be related to alterations in hypothalamic function.

  9. Oral administration of leaf extracts of Momordica charantia affect reproductive hormones of adult female Wistar rats

    PubMed Central

    Adewale, Osonuga Odusoga; Oduyemi, Osonuga Ifabunmi; Ayokunle, Osonuga

    2014-01-01

    Objective To determine the effect of graded doses of aqueous leaf extracts of Momordica charantia on fertility hormones of female albino rats. Methods Twenty adult, healthy, female Wistar rats were divided into four groups: low dose (LD), moderate dose (MD) and high dose (HD) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. Result Estrogen levels reduced by 6.40 nmol/L, 10.80 nmol/L and 28.00 nmol/L in the LD, MD and HD groups respectively while plasma progesterone of rats in the LD, MD and HD groups reduced by 24.20 nmol/L, 40.8 nmol/L and 59.20 nmol/L respectively. Conclusion Our study has shown that the antifertility effect of Momordica charantia is achieved in a dose dependent manner. Hence, cautious use of such medication should be advocated especially when managing couples for infertility. PMID:25183143

  10. Circadian variations in expression of the trkB receptor in adult rat hippocampus.

    PubMed

    Dolci, Claudia; Montaruli, Angela; Roveda, Eliana; Barajon, Isabella; Vizzotto, Laura; Grassi Zucconi, Gigliola; Carandente, Franca

    2003-12-19

    The expression of brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS) and the expression of its high-affinity trkB receptor on neuron surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and protein) and trkB mRNA shows circadian oscillations in rat hippocampal homogenates. We investigated circadian variations in trkB expression in specific areas of the adult rat hippocampal formation by immunohistochemistry. In sets of two experiments performed in the spring, 39 2-month-old male Wistar rats were accustomed to a 12-h light-12-h dark cycle for 2 weeks. Three animals were then sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal formation were obtained and processed for trkB immunohistochemistry. Cell staining intensity was assessed by image analysis of different hippocampal areas on five sections per animal. Circadian rhythmicity was evaluated by the cosinor method. Statistically significant circadian variations in trkB expression were found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the hippocampus, with highest expression during the first half of the dark (activity) period. These findings suggest a relationship between trkB expression and the physiological neuronal activation of wakefulness. TrkB receptor expression in the hippocampal regions studied was continuous and changes were gradual over the 24-h cycle, suggesting that more complex regulatory mechanisms also intervened.

  11. Protective effects of Peganum harmala extracts on thiourea-induced diseases in adult male rat.

    PubMed

    Hamden, Khaled; Masmoudi, Hatem; Ellouz, Feriel; ElFeki, Adelfatteh; Carreau, Serge

    2008-01-01

    Cancers and hepatoprotective prevention using traditional medicines have attracted increasing interest. The aim of our study was to characterize the putative protective effects of ethanol and chloroform extracts of Peganum harmala on thiourea-induced diseases in adult male rat. We seek to determine the effects of these plant extracts on body weight, thyroid and endocrine cancer parameters. In addition the putative hepatoprotective effect was checked by the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the bilirubin level in the blood. Our data show that ethanol and chloroform extracts of Peganum harmala protected the animal against the carcinogenic effects induced by thiourea since neuron-specific enolase (NSE) and thyroglobulin (TG) levels were back to the normal range. In addition, the observed-hepatocytotoxicity after thiourea treatment was greatly reduced (AST and ALT activities were respectively 270 IU/l and 60 IU/l and in the same order of magnitude as in the untreated rats) as well as the bilirubin levels (6 micromol/l) especially for animals receiving the choroform preparation. Therefore we may suggest that extracts of Peganum harmala are efficient to reduce the toxicity induced by thiourea in male rat as far as the above parameters are concerned.

  12. The Changing Nature of Adult Education in the Age of Transnational Migration: Toward a Model of Recognitive Adult Education

    ERIC Educational Resources Information Center

    Guo, Shibao

    2015-01-01

    This chapter examines the changing nature of adult education in the age of transnational migration and proposes recognitive adult education as an inclusive model that acknowledges and affirms cultural difference and diversity as positive and desirable assets.

  13. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect

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

    2011-09-15

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral

  14. Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

    PubMed Central

    Eladl, Mohamed Ahmed; M Elsaed, Wael; Atef, Hoda; El-Sherbiny, Mohamed

    2017-01-01

    Background Several renal disorders affect the glomerular podocytes. Compensatory structural and functional changes have been observed in animals that have undergone unilateral renal ablation. These changes occur as a pliant response to quench the increased functional demand to maintain homeostasis of fluid and solutes. Nestin is an intermediate filament protein present in the glomerular podocytes of the adult kidney and is linked with the maintenance of its foot process structure. Structural changes in the podocytes ultimately restructure the filtration barrier. Very few studies related to the ultrastructural and histopathologic changes of the podocytes are documented. The present study aimed to assess the histopathologic changes at the ultrastructural level in the adapted kidney at different time intervals following unilateral renal ablation in adult rats and its relation with nestin. Methods Forty-eight rats were divided into four groups (n=12 in each group). The animals of Group A were control naïve rats, while the group B, group C and group D animals underwent left unilateral nephrectomy and the remaining right kidney was removed on days 10, 20 and 30, respectively. Each group included four sham-operated rats, which were sacrificed at the same time as the naïve rats. Each nephrectomized sample was weighed and its sections were subjected to hematoxylin and eosin examination, transmission electron microscopic study as well as immunostaining using the intermediate filament protein nestin. Results No difference was found between the kidney sections from the control group and the sham-operated groups. A significant increase in the weight of the right kidneys was noted in groups B, C and D (P<0.001). The ultrastructural adaptive changes seen in the glomeruli of group B were subsequently reduced in groups C and D. This finding corresponded to a similar pattern of nestin expression in the podocytes, which showed significant increase in group B followed by reduced

  15. Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia

    PubMed Central

    Prieto-Lloret, Jesus; Ramirez, Maria; Olea, Elena; Moral-Sanz, Javier; Cogolludo, Angel; Castañeda, Javier; Yubero, Sara; Agapito, Teresa; Gomez-Niño, Angela; Rocher, Asuncion; Rigual, Ricardo; Obeso, Ana; Perez-Vizcaino, Francisco; González, Constancio

    2015-01-01

    Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55–60% O2 for the last 5–6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2-sensitivity of K+ currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life. Key points Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is

  16. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats.

    PubMed

    Ren, Ke; Novikova, Svetlana I; He, Fang; Dubner, Ronald; Lidow, Michael S

    2005-09-22

    Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR) injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors) to compare gene expression profiles in the lumbar spinal dorsal horn (LDH) of adult (P60) male rats that received neonatal CAR treatment within (at postnatal day 3; P3) and outside (at postnatal 12; P12) of the sensitive period. The data were obtained both without inflammation (at baseline) and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems) were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems) in the LDH ipsilateral to the neonatally-injured paw. The

  17. Signaling by TGF-betas in tubule cultures of adult rat testis

    PubMed Central

    Chan, Kai-Hui; Galuska, Sebastian P; Kudipudi, Pradeep Kumar; Riaz, Mohammad Assad; Loveland, Kate L; Konrad, Lutz

    2017-01-01

    Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1. In contrast, BMPs (BMP2 and BMP7) do not signal via the high-affinity type I and type II TGFβ receptors, TBR1 or TBR2. Furthermore, treatment of tubule cultures with either TGF-β1 or TGF-β2 had profound significant stimulatory effects on secretion of plasminogen activator-1 (PAI-1) through utilization of TGF-β and BMP receptors. Specific inhibitors for either TBR1 or BMP receptors yielded nearly complete inhibition of TGF-β signaling. The TBR1-TBR2 signalosome was detected with Duolink upon stimulation with either TGF-β1 or TGF-β2, predominantly in spermatogenic cells of the adult rat testis, particularly in elongated spermatids. In summary, this examination of intact rat testicular tubules demonstrated for the first time that TGF-βs signal mainly through TBR1 and TBR2 but also use BMP receptors, including for secretion of PAI-1. Whereas ALK2 participates in the TGF-β1-induced TBR1-TBR2 signalosome, ALK3 and ALK6 are involved in signaling of TGF-β2. Detection of the TBR1-TBR2 signalosome in late spermiogenic cells indicates a post-meiotic activity. PMID:28386343

  18. Immune responses in sprague-dawley rats exposed to dibutyltin dichloride in drinking water as adults.

    PubMed

    DeWitt, Jamie C; Copeland, Carey B; Luebke, Robert W

    2005-07-01

    Organotins are used commercially as agricultural pesticides, antifouling agents, and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern as they leach from supply pipes into drinking water and have been reported to cause multisystem toxicity, including immunotoxicity. As part of an ongoing study to evaluate immunotoxic effects of organotins, we assessed immune function in adult Sprague-Dawley (CD) rats after exposure to dibutyltin dichloride (DBTC). Individually-housed adult male and female CD rats were given drinking water containing 0, 10, or 25 mg DBTC/L (final concentration) in 0.5% Alkamuls for 28 days. Water bottles were changed and water consumption was monitored twice weekly and body weights (BW) were recorded weekly. Delayed-type hypersensitivity (DTH), primary and secondary antibody responses to sheep red blood cells, and natural killer (NK) cell activity were evaluated in separate groups of treated and control animals on day 29 of exposure. Water consumption was significantly decreased in both sexes at 25 mg DBTC/L. BW, immune organ weights, the DTH response, and NK cell activity did not vary by dose. Different results for antibody responses in male rats were obtained in two experimental replicates. In the first replicate, IgG was elevated at the highest dose whereas in the second replicate, IgM was suppressed. However, as these effects occurred at the high dose of 25 mg DBTC/L, which is a concentration a million times higher than levels of DBTC reported in drinking water, our data suggest that DBTC is unlikely to cause immunotoxicity at concentrations found in drinking water supplies.

  19. Identification of interneurons activated at different inclines during treadmill locomotion in adult rats.

    PubMed

    Tillakaratne, Niranjala J K; Duru, Paul; Fujino, Hidemi; Zhong, Hui; Xiao, Mei Si; Edgerton, V Reggie; Roy, Roland R

    2014-12-01

    By using c-fos as an activity-dependent marker, we identified the cholinergic interneurons around the central canal and lumbar interneurons throughout the gray matter that were activated after a 30-min bout of quadrupedal treadmill stepping at a 0° or 25° incline in adult rats. Increased loading (elevated treadmill incline) imposed during treadmill stepping activated more cholinergic interneurons in the proximity of the central canal, i.e., central canal cluster cells and partition neurons. Since cholinergic central canal cells are thought to modulate motoneuron excitability, these data suggest that increased load during stepping may increase motoneuronal activity through activating more cholinergic central canal cells. We identified the muscle-specific motoneurons and afferent terminals in the spinal cord by injecting cholera toxin subunit B in the soleus and tibialis anterior muscles. The number of interneurons in lumbar segments L4 (tibialis anterior) and L5 (soleus) was higher in both groups that stepped on the treadmill compared with control and was highest in rats that stepped at a 25° incline. In a majority of laminae, the distribution of total and muscle-specific activated interneurons was highest in the 25° incline group and lowest in the control group for both muscles. These data could reflect increased peripheral (proprioceptive) input as well as supraspinal drive associated with stepping and demonstrate the differences in 1) the activation of cholinergic interneurons near the central canal and 2) the laminar and segmental location of interneurons throughout the gray matter that play a role in generating stepping under different loading conditions in adult rats.

  20. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats.

    PubMed

    Ellgren, Maria; Spano, Sabrina M; Hurd, Yasmin L

    2007-03-01

    Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 microg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 microg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 microg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

  1. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  2. Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test

    PubMed Central

    Onifer, Stephen M.; Reed, William R.; Sozio, Randall S.; Long, Cynthia R.

    2015-01-01

    Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats (n = 12) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n = 12) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1–5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P < 0.001). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted. PMID:26693243

  3. Developmental effects of wheel running on hippocampal glutamate receptor expression in young and mature adult rats.

    PubMed

    Staples, M C; Somkuwar, S S; Mandyam, C D

    2015-10-01

    Recent evidence suggests that the behavioral benefits associated with voluntary wheel running in rodents may be due to modulation of glutamatergic transmission in the hippocampus, a brain region implicated in learning and memory. However, the expression of the glutamatergic ionotropic N-methyl-d-aspartate receptor (GluN) in the hippocampus in response to chronic sustained voluntary wheel running has not yet been investigated. Further, the developmental effects during young and mature adulthood on wheel running output and GluN expression in hippocampal subregions has not been determined, and therefore is the main focus of this investigation. Eight-week-old and 16-week-old male Wistar rats were housed in home cages with free access to running wheels and running output was monitored for 4weeks. Wheel access was terminated and tissues from the dorsal and ventral hippocampi were processed for Western blot analysis of GluN subunit expression. Young adult runners demonstrated an escalation in running output but this behavior was not evident in mature adult runners. In parallel, young adult runners demonstrated a significant increase in total GluN (1 and 2A) subunit expression in the dorsal hippocampus (DH), and an opposing effect in the ventral hippocampus (VH) compared to age-matched sedentary controls; these changes in total protein expression were not associated with significant alterations in the phosphorylation of the GluN subunits. In contrast, mature adult runners demonstrated a reduction in total GluN2A expression in the DH, without producing alterations in the VH compared to age-matched sedentary controls. In conclusion, differential running activity-mediated modulation of GluN subunit expression in the hippocampal subregions was revealed to be associated with developmental effects on running activity, which may contribute to altered hippocampal synaptic activity and behavioral outcomes in young and mature adult subjects.

  4. Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens.

    PubMed

    Alaux-Cantin, Stéphanie; Warnault, Vincent; Legastelois, Rémi; Botia, Béatrice; Pierrefiche, Olivier; Vilpoux, Catherine; Naassila, Mickaël

    2013-04-01

    Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism. However, mechanisms underlying this susceptibility remain unknown. We evaluated the effect of adolescent binge-like ethanol intoxication on vulnerability to alcohol abuse in Sprague-Dawley rats. To model binge-like ethanol intoxication, every 2 days, rats received an ethanol injection (3.0 g/kg) for 2 consecutive days across 14 days either from postnatal day 30 (PND30) to 43 (early adolescence) or from PND 45 to PND 58 (late adolescence). In young adult animals, we measured free ethanol consumption in the two-bottle choice paradigm, motivation for ethanol in the operant self-administration task and both ethanol's rewarding and aversive properties in the conditioned place preference (CPP) and taste aversion (CTA) paradigms. While intermittent ethanol intoxications (IEI) during late adolescence had no effect on free-choice 10% ethanol consumption, we found that IEI during early adolescence promoted free-choice 10% ethanol consumption, enhanced motivation for ethanol in the self-administration paradigm and induced a loss of both ethanol-induced CPP and CTA in young adults. No modification in either sucrose self-administration or amphetamine-induced CPP was observed. As the nucleus accumbens (Nac) is particularly involved in addictive behavior, we analyzed IEI-induced long-term neuroadaptations in the Nac using c-Fos immunohistochemistry and an array of neurotransmission-related genes. This vulnerability to ethanol abuse was associated with a lower c-Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission-related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism.

  5. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD we