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Sample records for adult rat model

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. A Novel Model of Surgical Injury in Adult Rat Kidney: A “Pouch Model”

    PubMed Central

    Litbarg, Natalia O.; Vujicic, Snezana; Setty, Suman; Sethupathi, Periannan; Dunea, George; Arruda, Jose A.; Singh, Ashok K.

    2013-01-01

    Regenerative mechanisms after surgical injury have been studied in many organs but not in the kidney. Studying surgical injury may provide new insights into mechanisms of kidney regeneration. In rodent models, extrarenal tissues adhere to surgical kidney wound and interfere with healing. We hypothesized that this can be prevented by wrapping injured kidney in a plastic pouch. Adult rats tolerated 5/6 nephrectomy with pouch application well. Histological analysis demonstrates that application of the pouch effectively prevented formation of adhesions and induced characteristic wound healing manifested by formation of granulation tissue. Additionally, selected tubules of the wounded kidney extended into the granulation tissue forming branching tubular epithelial outgrowths (TEOs) without terminal differentiation. Tubular regeneration outside of renal parenchyma was not previously observed, and suggests previously unrecognized capacity for regeneration. Our model provides a novel approach to study kidney wound healing. PMID:24100472

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2006-03-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2012-12-01

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

  10. Electroacupuncture upregulates ERK signaling pathways and promotes adult hippocampal neural progenitors proliferation in a rat model of depression

    PubMed Central

    2013-01-01

    Background In this study, we investigate the proliferation of adult neural stem cells (NSCs) in a chronic unpredictable stress (CUS) rat model of depression, the effects of electroacupunture (EA) on depressive-like symptoms and the corresponding signaling pathways. Methods SD rats were subjected to 4 weeks of CUS to induce depressive-like behaviors. EA was performed at the Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan) acupoints. Rats were injected with BrdU and the brains were cut into sections. Double-labeling with BrdU/Sox2 and p-ERK/Nestin was performed to demonstrate the in vivo proliferation of adult NSCs in hippocampus and ERK activation in NSCs. Hippocampal microdialysates of different groups were collected to observe the in vitro effects on NSCs. Results After 8 treatments, EA generated a clear antidepressant effect on the stressed rats and promoted the NSC proliferation. ERK activation might be involved in the antidepressant-like effects of EA treatment. Hippocampal microdialysates from EA-treated stressed rats influenced NSCs to form larger neural spheres and exhibit higher p-ERK level in vitro, compared to the untreated stressed rats. Meanwhile, the antidepressant-like effects of EA involved contribution from both acupoint specificity and electrical stimulus. Conclusions EA might interfere with the hippocampal microenvironment and enhance the activation of ERK signaling pathways. This could mediate, at least in part, the beneficial effects of EA on NSC proliferation and depressive-like behaviors. PMID:24165147

  11. 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

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

    PubMed

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

    2016-04-01

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

  13. A comparison of different models with motor dysfunction after traumatic brain injury in adult rats.

    PubMed

    Wang, Meng; Pu, Hongjian; Liu, Yingchao; Wang, Zengtao; Wang, Bomin; Xu, Wendong

    2014-12-01

    The aim of this study was to evaluate the validity of the model that could produce reproducible and persistent motor weakness and define the accurate tasks and testing parameters for longitudinal assessment of neurological deficits after traumatic brain injury (TBI). We compared the effects of two rat models that suffered different controlled cortical impact (CCI) injury, as well as extensive motor cortex resection model, on behavior recovery and brain morphology. Behavioral tests including the skilled reaching task, limb-use asymmetry test and the grasping test were employed to evaluate neurofunctional recovery from pre- to 12 weeks after the injury. The results demonstrated that all the rats in four groups showed spontaneous functional improvement with the past of time after surgery, especially in rats with mild and moderate CCI injury. At the end of the experiment, the animals' performance reached preoperative base lines on reaching task and limb-use asymmetry test in mild and moderate groups, while severe motor weakness could be observed in rats with severe CCI injury, as well as rats with extended motor cortex resection. Overall, the results of this study indicated that both models with severe CCI injury and extended resection of the motor cortex developed reproducible and long-lasting motor weakness, comparable in severity and duration and identified skilled reaching task, as well as limb-use asymmetry test, as sensitive assessments for slight neurological deficits after brain injury. This will help to provide the basis for further research of the processes after the TBI and development of novel therapies. PMID:25385190

  14. 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. PMID:26657171

  15. Nicotine-induced behavioral sensitization in an adult rat model of attention deficit/hyperactivity disorder (ADHD).

    PubMed

    Watterson, Elizabeth; Spitzer, Alexander; Watterson, Lucas R; Brackney, Ryan J; Zavala, Arturo R; Olive, M Foster; Sanabria, Federico

    2016-10-01

    Attention deficit hyperactivity disorder (ADHD) is associated with increased risk of tobacco dependence. Nicotine, the main psychoactive component of tobacco, appears to be implicated in ADHD-related tobacco dependence. However, the behavioral responsiveness to nicotine of the prevalent animal model of ADHD, the spontaneously hypertensive rat (SHR), is currently underinvestigated. The present study examined the activational effects of acute and chronic nicotine on the behavior of adult male SHRs, relative to Wistar Kyoto (WKY) controls. Experiment 1 verified baseline strain differences in open-field locomotor activity. Experiment 2 tested for baseline strain differences in rotational behavior using a Rotorat apparatus. Adult SHR and WKY rats were then exposed to a 7-day regimen of 0.6mg/kg/d s.c. nicotine, or saline, prior to each assessment. A separate group of SHRs underwent similar training, but was pre-treated with mecamylamine, a cholinergic antagonist. Nicotine sensitization, context conditioning, and mecamylamine effects were then tested. Baseline strain differences were observed in open-field performance and in the number of full rotations in the Rotorat apparatus, but not in the number of 90° rotations or direction changes. In these latter measures, SHRs displayed weaker nicotine-induced rotational suppression than WKYs. Both strains expressed nicotine-induced sensitization of rotational activity, but evidence for strain differences in sensitization was ambiguous; context conditioning was not observed. Mecamylamine reversed the effects of nicotine on SHR performance. These findings are consistent with the hypothesis that a reduced aversion to nicotine (expressed in rats as robust locomotion) may facilitate smoking among adults with ADHD. PMID:27363925

  16. Assessing the effects of model Maillard compound intake on iron, copper and zinc retention and tissue delivery in adult rats.

    PubMed

    Roncero-Ramos, Irene; Pastoriza, Silvia; Navarro, M Pilar; Delgado-Andrade, Cristina

    2016-01-01

    The behaviour of dietary Maillard reaction compounds (MRP) as metal chelating polymers can alter mineral absorption and/or retention. Our aim in this study was to analyse the long-term effects of the consumption of model MRP from glucose-lysine heated for 90 min at 150 °C (GL) on iron, copper and zinc whole-body retention and tissue delivery. For 88 days, weaning rats were fed a Control diet or one containing 3% GL, until reaching the adult stage. During the experimental period a mineral balance was conducted to investigate the mineral retention. At day 88, the animals were sacrificed, blood was drawn for haemoglobin determination and some organs were removed. Copper and zinc balances were unaffected (Cu: 450 vs. 375 μg; Zn: 6.7 vs. 6.2 mg for Control and GL groups, respectively) and no change was observed in whole-body delivery. Iron retention, too, was unaltered (11.2 mg for Control and GL groups) but due to the tendency toward decreased body weight in the GL group (248 vs. 233 g for the Control and GL groups), whole-body iron concentration was 13% higher in the GL group than in the Control group. Absorbed iron accumulated particularly in the liver (144 vs. 190 μg g(-1) for the Control and GL groups), thus reducing haemoglobin levels. The long-term intake of MRP induced iron accumulation in the body but this did not result in enhanced iron functionality, since the haemoglobin concentration declined. Taking into account the findings of our research group's studies of young and adult rats, we now corroborate the hypothesis that the negative effect of GL MRP consumption on iron functionality takes place regardless of the animals' stage of life. PMID:26593232

  17. 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. PMID:24882551

  18. 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

  19. 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

  20. 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 ...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. Injection time-dependent effect of adult human bone marrow stromal cell transplantation in a rat model of severe traumatic brain injury.

    PubMed

    Han, Eun Young; Chun, Min Ho; Kim, Sang Tae; Lim, Dong-pyo

    2013-03-01

    The object of this study is to evaluate the effects of injecting adult human bone marrow stromal cells (hBMSCs) into rats with severe traumatic brain injury in acute phase and to determine more optimal injection timing between day 1 and day 2 postinjury. The lateral fluid percussion injury model was used. Adult hBMSCs were transplanted into hemisphere to injury sites in the corpus callosum ipsilateral on day 1 (n = 12) or day 7 (n = 8) after injury. A control group (n = 7) underwent only a sham operation without stem cell transplantation. Rats in all groups were analyzed by magnetic resonance spectroscopy (MRS), and by using behavioral, rotarod, and Barnes maze tests on day 1, 7, 14, and 42. Another nine randomly designated rats were sacrificed for immunohistochemical staining. Behavioral test scores increased significantly at all time-points after TBI in the day 7-injected group, compared to the others (p=0.008). GFAP staining was lower on day 42 in day 7-injected rats than in those injected on day 1. But no significant inter- or intra-group differences were observed for other tests. The injection of hBMSCs was found to have limited therapeutic potential with respect to neuroprotection after traumatic brain injury. However, because injection on day 7 after TBI produced greater functional improvements in neurobehavioral tests and more effectively suppressed astroglial activation than an injection on post-injury day 1, we cautiously recommend the injection time of day 7 post injury in hBMSCs transplantation in severe TBI, rather than day 1 post injury but further studies on developing hBMSC-based new therapeutic approaches should be warranted for improving neuroprotection in severe TBI. PMID:23363468

  5. 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

  6. 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

  7. Self-assembled adult adipose-derived stem cell spheroids combined with biomaterials promote wound healing in a rat skin repair model.

    PubMed

    Hsu, Shan-Hui; Hsieh, Pai-Shan

    2015-01-01

    Adult adipose-derived stem cells (ASCs) are a type of multipotent mesenchymal stem cells (MSCs) with easy availability and serve as a potential cell source for cell-based therapy. Three-dimensional MSC spheroids may be derived from the self-assembly of individual MSCs grown on certain polymer membranes. In this study, we demonstrated that the self-assembled ASC spheroids on chitosan-hyaluronan membranes expressed more cytokine genes (fibroblast growth factor 1, vascular endothelial growth factor, and chemokine [C-C motif] ligand 2) as well as migration-associated genes (chemokine [C-X-C motif] receptor type 4 and matrix metalloprotease 1) compared with ASC dispersed single cells grown on culture dish. To evaluate the in vivo effects of these spheroids, we applied ASC single cells and ASC spheroids in a designed rat skin repair model. Wounds of 15 × 15 mm were created on rat dorsal skin, where ASCs were administered and covered with hyaluronan gel/chitosan sponge to maintain a moist environment. Results showed that skin wounds treated with ASC spheroids had faster wound closure and a significantly higher ratio of angiogenesis. Tracking of fluorescently labeled ASCs showed close localization of ASC spheroids to microvessels, suggesting enhanced angiogenesis through paracrine effects. Based on the in vitro and in vivo results, the self-assembled ASC spheroids may be a promising cellular source for skin tissue engineering and wound regeneration. PMID:25421559

  8. 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

  9. Interactions between respiratory oscillators in adult rats.

    PubMed

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

    2016-01-01

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

  10. 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

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

    EPA Science Inventory

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

  12. TRIMETHYLTIN DISRUPTS ACOUSTIC STARTLE RESPONDING IN ADULT RATS

    EPA Science Inventory

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

  13. 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...

  14. Impaired pancreatic duct-cell growth in focal areas of regeneration after partial pancreatectomy in the adult Goto-Kakizaki rat, a spontaneous model of non-insulin dependent diabetes mellitus.

    PubMed

    Plachot, C; Portha, B

    2001-03-01

    The Paris colony of adult Goto-Kakizaki (GK/Par) rat, a genetic model of non-insulin dependent diabetes mellitus, is characterized by a restriction of the beta-cell mass and reduced beta-cell regeneration capacity. In order to have a better understanding of the impaired mechanism(s) leading to reduced beta-cell plasticity in the GK/Par rat, we have investigated duct-cell growth capacity following 90% pancreatectomy, a well-defined procedure leading in non-diabetic rats, to sequential duct proliferation and subsequent differentiation. To this aim, we have performed pancreatectomy in 8-10-week-old male normoglycaemic Wistar and diabetic GK rats. Duct-cell proliferation and apoptosis were evaluated at different time points: day 0 (D0), day 2 (D2), day 7 (D7) and day 14 (D14) after pancreatectomy. A transient wave of duct-cell proliferation was observed on D2 in both small and main ducts in the pancreatectomized Wistar rats. A similar increase occurred in the similarly treated GK rats, but to a higher extent as compared to the Wistar rats. Thereafter, duct-cell proliferation from main or small ducts returned to non-pancreatectomized values on D7 and remained at this level on D14 in both the Wistar and GK pancreatectomized groups. In the common pancreatic duct, the number of proliferative duct-cells was higher in GK rats compared to Wistar on D0. In both the operated Wistar and GK rats, duct-cell proliferation from the common pancreatic duct similarly decreased on D2. On D7 and D14, the same parameter returned to non-pancreatectomized values in the Wistar rats, while it was maintained lower in the GK rats as compared to the GK values on D0. In focal areas of regeneration, duct-cell proliferation was significantly lower in the pancreatectomized GK group compared to the age-related Wistar group on D7 (Wistar: 5.85+/-0.98%, GK: 3.02+/-0.69%; p < 0.01) and D14 (Wistar: 3.82+/-0.29%, GK: 2.62+/-0.27%; ns). Only a few apoptotic duct-cells were observed, with no difference

  15. 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

  16. 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.

  17. 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…

  18. 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

  19. 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.

  20. Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

    PubMed Central

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

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes. PMID:23301065

  1. 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.

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

    PubMed

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

    2016-10-01

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

  3. ACUTE TOXICITY OF PESTICIDES IN ADULT AND WEANLING RATS

    EPA Science Inventory

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    1999-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-15

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2009-02-01

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

  12. BMP3 expression in the adult rat CNS.

    PubMed

    Yamashita, Kanna; Mikawa, Sumiko; Sato, Kohji

    2016-07-15

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

  13. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2006-04-12

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

  17. 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.

  18. 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

  19. A novel rat model for chemotherapy-induced alopecia

    PubMed Central

    Wikramanayake, T. C.; Amini, S.; Simon, J.; Mauro, L. M.; Elgart, G.; Schachner, L. A.; Jimenez, J. J.

    2011-01-01

    Summary Background More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. Aim To develop a clinically relevant adult rat model for CIA. Methods We first tested whether neonatal pigmented Long–Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle. and starting 15 days later, the rats were treated with etoposide for 3 days. Results Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. Conclusions A novel, pigmented adult rat model has been established for CIA. By hair shaft clipping during early telogen, synchronized anagen entry was induced that resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA and will be a useful tool to test agents for the prevention and treatment of CIA. PMID:22409523

  20. 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.

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

    PubMed Central

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

    2015-01-01

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

  2. Mesenteric lymph flow in adult and aged rats.

    PubMed

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

    2011-11-01

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

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

    PubMed

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

    2013-12-01

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

  5. 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.

  6. 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

  7. 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

  8. 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. PMID:25975172

  9. Modeling nicotine addiction in rats.

    PubMed

    Caille, Stephanie; Clemens, Kelly; Stinus, Luis; Cador, Martine

    2012-01-01

    Among the human population, 15% of drug users develop a pathological drug addiction. This figure increases substantially with nicotine, whereby more than 30% of those who try smoking develop a nicotine addiction. Drug addiction is characterized by compulsive drug-seeking and drug-taking behaviors (craving), and loss of control over intake despite impairment in health, social, and occupational functions. This behavior can be accurately modeled in the rat using an intravenous self-administration (IVSA) paradigm. Initial attempts at establishing nicotine self-administration had been problematic, yet in recent times increasingly reliable models of nicotine self-administration have been developed. The present article reviews different characteristics of the nicotine IVSA model that has been developed to examine nicotine reinforcing and motivational properties in rats. PMID:22231818

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

    PubMed

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

    2011-06-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2005-03-15

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

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

    PubMed

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

    1995-05-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  19. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

    PubMed

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

    2016-06-01

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

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

    PubMed

    Schneider, Miriam; Koch, Michael

    2003-10-01

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

  1. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

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

    2009-01-01

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

  2. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

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

  3. 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

  4. 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. PMID:25312505

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

    PubMed

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

    2011-11-01

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

  6. 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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    1988-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. 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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  14. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

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

    2009-06-01

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

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

    PubMed

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

    2008-02-01

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

  16. 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...

  17. Behavioral Differences Between Late Preweanling and Adult Female Sprague-Dawley Rat Exploration of Animate and Inanimate Stimuli and Food

    PubMed Central

    Smith, Kiersten S.; Morrell, Joan I.

    2010-01-01

    The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied stimuli, including inanimate objects systematically varied in size and interactive properties, biological stimuli, and food. Preweanlings were faster to initiate specific stimulus exploration and were more interactive with most specific stimuli than adults; the magnitude of these preweanling-adult quantitative differences ranged from fairly small to very large depending upon the stimulus. In contrast, preweanlings were adult-like in their interaction with food and prey. Preweanling response to some stimuli, for example to live pups, was qualitatively different from that of adults; the preweanling behavioral repertoire was characterized by pup-seeking while the adult response was characterized by pup-avoidance. The specific stimulus interactions of preweanlings were less impacted than those of adults by the time of day of testing and placement of a stimulus in an anxiety-provoking location. The impact of novelty was stimulus dependent. The differences in interactions of preweanlings versus adults with specific stimuli suggests that CNS systems underlying these behavior patterns are at different stages of immaturity at PND 18 such that there may be an array of developmental trajectories for various categories of specific stimuli. These data provide a basis for the use of the preweanling as a preclinical model for understanding and medicating human disorders during development that are characterized by dysfunctional interactions with specific stimuli. PMID:21056059

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

    EPA Science Inventory

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

  19. 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.

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

    PubMed

    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. PMID:18758003

  1. 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 (...

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Dlugos, Cynthia A

    2015-08-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2000-11-15

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

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

    PubMed

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

    2006-09-01

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

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

    PubMed Central

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

    1996-01-01

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

  10. Flux control exerted by overt carnitine palmitoyltransferase over palmitoyl-CoA oxidation and ketogenesis is lower in suckling than in adult rats.

    PubMed Central

    Krauss, S; Lascelles, C V; Zammit, V A; Quant, P A

    1996-01-01

    We examined the potential of overt carnitine palmitoyltransferase (CPT I) to control the hepatic catabolism of palmitoyl-CoA in suckling and adult rats, using a conceptually simplified model of fatty acid oxidation and ketogenesis. By applying top-down control analysis, we quantified the control exerted by CPT I over total carbon flux from palmitoyl-CoA to ketone bodies and carbon dioxide. Our results show that in both suckling and adult rat, CPT I exerts very significant control over the pathways under investigation. However, under the sets of conditions we studied, less control is exerted by CPT I over total carbon flux in mitochondria isolated from suckling rats than in those isolated from adult rats. Furthermore the flux control coefficient of CPT I changes with malonyl-CoA concentration and ATP turnover rate. PMID:8912677

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  14. 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...

  15. The effects of early-life predator stress on anxiety- and depression-like behaviors of adult rats.

    PubMed

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  16. The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

    PubMed Central

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  17. 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.

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

    PubMed

    Panadero, Maribel; Herrera, Emilio; Bocos, Carlos

    2005-01-14

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

  19. 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

  20. Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

    PubMed Central

    Tajuddin, Nuzhath; Moon, Kwan-Hoon; Marshall, S. Alex; Nixon, Kimberly; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2014-01-01

    Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  1. Enriched Environment Altered Aberrant Hippocampal Neurogenesis and Improved Long-Term Consequences After Temporal Lobe Epilepsy in Adult Rats.

    PubMed

    Zhang, Xiaoqian; Liu, Tingting; Zhou, Zhike; Mu, Xiaopeng; Song, Chengguang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

    2015-06-01

    Abnormal hippocampal neurogenesis is thought to contribute to cognitive impairments in chronic temporal lobe epilepsy (TLE). Stromal cell-derived factor-1 (SDF-1) and its specific receptor CXCR4 play important roles in neurogenesis. We investigated whether enriched environment (EE) might be beneficial for TLE. Adult rats were randomly assigned as control rats, rats subjected to status epilepticus (SE), or post-SE rats treated with EE for 30 days. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze. Western blot was used to measure the expression of SDF-1 and CXCR4 in the hippocampus. In the present study, we found the TLE model resulted in aberrant neurogenesis such as reduced proliferation, intensified dendritic development of newborn neurons, as well as spontaneous seizures and cognitive impairments. More importantly, EE treatment significantly increased the cell proliferation and survival, extended the apical dendrites, and delayed the attenuation of the expression of SDF-1 and CXCR4, accompanied by decreased long-term seizure activity and improved cognitive impairments in adult rats after TLE. These results provided morphological evidence that EE might be beneficial for treating TLE. PMID:25946980

  2. The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

    PubMed

    Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

    2015-09-14

    Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. PMID:26238258

  3. 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. PMID:25479965

  4. Neonatal stress from limited bedding elicits visceral hyperalgesia in adult rats.

    PubMed

    Guo, Yumei; Wang, Zhuo; Mayer, Emeran A; Holschneider, Daniel P

    2015-01-01

    Early life stress is a risk factor for developing functional pain disorders. The 'limited bedding' (LB) model elicits psychological stress in the dam and her pups by providing minimal nesting material following delivery. Little is known about the effects of LB on visceral pain. Rats (female, male) were exposed to LB on postnatal days 2-9. Electromyographic visceromotor responses were recorded at the age of 11-12 weeks during titrated colorectal distension. LB exposure resulted in significant visceral hyperalgesia in both sexes. Sex differences were demonstrated only in nonstressed controls, with females showing a greater visceromotor response. Our results prepare the way for use of the LB model in studying the development of visceral pain in adults with functional gastrointestinal disorders. PMID:25426824

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

    PubMed

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

    2015-12-01

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

  6. Temperament moderates the influence of periadolescent social experience on behavior and adrenocortical activity in adult male rats

    PubMed Central

    Caruso, M.J.; McClintock, M.K.; Cavigelli, S.A.

    2014-01-01

    Adolescence is a period of significant behavioral and physiological maturation, particularly related to stress responses. Animal studies that have tested the influence of adolescent social experiences on stress-related behavioral and physiological development have led to complex results. We used a rodent model of neophobia to test the hypothesis that the influence of adolescent social experience on adult behavior and adrenocortical function is modulated by preadolescent temperament. Exploratory activity was assessed in 53 male Sprague-Dawley rats to classify temperament and then they were housed in one of three conditions during postnatal days (PND) 28-46: (1) with familiar kin, (2) with novel social partners, or (3) individually with no social partners. Effects on adult adrenocortical function were evaluated from fecal samples collected while rats were individually-housed and exposed to a 1-hour novel social challenge during PND 110-114. Adolescent-housing with novel or no social partners led to reduced adult glucocorticoid production compared to adolescent-housing with familiar littermates. Additionally, highly-exploratory pre-weanling rats that were housed with novel social partners during adolescence exhibited increased exploratory behavior and a more rapid return to basal glucocorticoid production in adulthood compared to those housed with familiar or no social partners during adolescence and compared to low-exploratory rats exposed to novel social partners. In sum, relatively short-term adolescent social experiences can cause transient changes in temperament and potentially longer-term changes in recovery of glucocorticoid production in response to adult social challenges. Furthermore, early temperament may modulate the influence of adolescent experiences on adult behavioral and adrenocortical function. PMID:25066485

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2016-10-01

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

  10. Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring

    PubMed Central

    Wilson, Christina A.; Terry, Alvin V.

    2013-01-01

    Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the α7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

  11. A preliminary study of age-related difference in resistance to sepsis in the rat model.

    PubMed

    Wei, C I; Gilliam, M C; Cohen, M D; Cornell, J A; Moazam, F

    1987-11-01

    Although the pathophysiology of intraabdominal sepsis is well established in the adult animal, there is a paucity of similar information in the newborn animal. Using the Wichterman (K.A. Wichterman, A.E. Baue, and I.H. Chaudry, Journal of Surgical Research 29: 189, 1980) model of intraabdominal sepsis, 42 Sprague-Dawley suckling rat pups and 42 adults underwent cecal ligation followed by a single needle puncture of the cecum. Whereas a mortality of 47.6% was noted in the adult animals, only 7.1% of the suckling animals succumbed by the end of 1 week. After the ip LD50 of Escherichia coli was determined independently in each age group, appropriate doses of the bacteria were injected into the peritoneums of 36 suckling and 30 adult rats. The peritoneal fluid was aspirated at 0, 2, 4, 8, 24, and 48 hr and the bacterial concentration in the suspension was determined. The rate of bacterial clearance from the peritoneum of the suckling rats was found to be significantly greater at 2, 4, and 8 hr as compared with the adult animal. In vitro assay of the phagocytic activity of the peritoneal macrophages demonstrated a significantly higher activity in the cells obtained from the suckling rats than in those from the adult (P less than 0.05). A more efficient bacterial clearance and a higher phagocytic activity in the peritoneal macrophages of the suckling rats may contribute to the difference in the mortality between the two age groups. PMID:3316844

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

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2016-07-01

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

  13. 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.

  14. 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.

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

    PubMed

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

    2013-11-01

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

  16. Locomotor activity changes in female adolescent and adult rats during repeated treatment with a cannabinoid or club drug.

    PubMed

    Wiley, Jenny L; Evans, Rhys L; Grainger, Darren B; Nicholson, Katherine L

    2011-01-01

    Adolescents and young adults of both sexes are the primary consumers of "club" drugs; yet, most of the mechanistic preclinical research in this area has been performed in adult male rodents. The purpose of this study was to evaluate the acute and repeated effects of drugs that are commonly abused by adolescents in female adolescent and adult rats in a rodent model of behavioral sensitization. During two five-day periods separated by a two-day break, rats were injected daily with saline or with one of the following drugs: cocaine (7 or 15 mg/kg), ketamine (3 or 10 mg/kg), 3,4-methylenedioxymethamphetamine (MDMA) (3, 10, or 30 mg/kg), or Δ(9)-tetrahydrocannabinol (THC) (0.03, 0.1, 0.3 or 1 mg/kg) and their locomotor activity was measured. Cocaine increased activity across days in both age groups. Whereas ketamine produced progressive increases in activity with repeated administration in rats of both ages, MDMA increased, and then decreased, activity in the chronic dosing regimen in female adolescents only. Tolerance to the initial stimulatory effects of low doses of THC was observed at both ages. The results with THC are similar to those obtained for male rats tested under identical conditions in a previous study; however, in contrast with the present results in females, male adolescent rats in the previous study failed to develop behavioral sensitization to ketamine. Together, these results suggest that age and sex strongly influence the progressive adaptive changes that occur with repeated administration of some, but not all, of these commonly abused substances. PMID:22180350

  17. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring.

    PubMed

    O'Loan, Jonathan; Eyles, Darryl W; Kesby, James; Ko, Pauline; McGrath, John J; Burne, Thomas H J

    2007-04-01

    Developmental vitamin D (DVD) deficiency alters brain development and behaviour in the rat. The aim of this study was to vary levels of vitamin D deficiency during gestation and examine the effects on developmental milestones and behaviour in adult offspring. By manipulating the withdrawal and reintroduction of vitamin D in the diet of female Sprague-Dawley rats, their offspring were subjected to four different prenatal vitamin D conditions: (a) control (normal vitamin D throughout gestation); (b) early-DVD deficiency; (c) late-DVD deficiency; and (d) full-DVD deficiency. We show that the standard measure for vitamin D status, 25(OH)D(3), can be significantly manipulated within 7 days by dietary intervention. We also show that levels of the active form of this vitamin, 1,25(OH)(2)D(3), replete within the same time frame as 25(OH)D(3) but are slower to deplete. Developmental milestones remained normal across all four dietary groups. Concerning the adult behavioural phenotype, both full- and late-DVD deficiency were associated with MK-801-induced hyperlocomotion. Overall, these data suggest that vitamin D deficiency restricted to late gestation only is sufficient to disrupt adult brain functioning in the rat. These findings suggest there may be a therapeutic window for maternal dietary intervention in the DVD model of psychosis. PMID:17276604

  18. Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats.

    PubMed

    Iwamoto, J; Takeda, T; Katsumata, T; Tanaka, T; Ichimura, S; Toyama, Y

    2002-02-01

    The purpose of the present study was to determine whether etidronate treatment could prevent bone loss caused by orchidectomy (ORX) and unilateral sciatic neurectomy (NX) in adult male rats. Seventy-four male Wistar rats, aged 10 months, were randomly divided into eight groups: baseline controls (n = 10); age-matched sham-operated controls (AMC; n = 9); ORX (n = 9); NX (n = 10); ORX + NX (n = 9); ORX + etidronate treatment (ORX + E; n = 7); NX + E (n = 10); and ORX + NX + E (n = 10). Etidronate treatment (10 mg/kg per day subcutaneously) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, bone mineral density (BMD) of the proximal and middle tibia (PT and MT, respectively), distal and middle femur (DF and MF, respectively), and fourth lumbar vertebral body (LVB) was measured by dual-energy X-ray absorptiometry (Model DCS-600, Aloka, Tokyo, Japan). The mechanical properties of the MF and third LVB were measured by three-point bending and compression tests, respectively. Levels of urinary deoxypyridinoline (Dpd) and serum osteocalcin (Oc) were also measured by enzyme-linked immunosorbent assay. Four weeks of aging had no significant effects on BMD, bone mechanical properties, or bone markers. ORX significantly increased the levels of urinary Dpd and serum Oc, which resulted in significant decreases in BMD of the PT, MT, DF, MF, and fourth LVB, as well as the mechanical strength (maximum load) of the MF and third LVB. NX significantly increased levels of urinary Dpd and decreased levels of serum Oc, resulting in a significant decrease in BMD of the PT, DF, and fourth LVB. The ORX-induced decrease in BMD of the PT was more pronounced when combined with NX. Etidronate treatment for NX, ORX, and ORX + NX rats significantly decreased levels of urinary Dpd and serum Oc, resulting in complete prevention of loss of BMD and/or bone mechanical strength. The present study demonstrates the efficacy of etidronate treatment for prevention

  19. Adult Children of Alcoholics: A Counseling Model.

    ERIC Educational Resources Information Center

    Crawford, Robert L.; Phyfer, Ann Quinn

    1988-01-01

    Notes that adult children of alcoholics attending college present unique problems and opportunities to the college counselor. Presents a treatment model for serving such students which identifies four survivor roles and their manifestations, and suggests counseling techniques for each role. (Author/NB)

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

    PubMed Central

    Mustroph, M.L.; King, M.A.; Klein, R.L.; Ramirez, J.J.

    2012-01-01

    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. PMID:22561128

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

    PubMed

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

    2012-05-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-07-01

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

  4. Traumatic arteriogenic erectile dysfunction: a rat model.

    PubMed

    El-Sakka, A; Yen, T S; Lin, C S; Lue, T F

    2001-06-01

    We developed a rat model of traumatic arteriogenic erectile dysfunction (ED) for the study of vasculogenic ED. Bilateral ligation of the internal iliac artery was performed on 30 three-month old male Sprague-Dawley rats as an experimental group. The control group consisted of 12 rats which underwent dissection of the internal iliac artery without ligation. Before their euthanization at 3 days, 7 days, and 1 month (10 rats in the experimental group and four rats in the control group at each time point), erectile function was assessed by electrostimulation of the cavernous nerves. Penile tissues were collected for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining, trichrome staining, electron microscopy and RT-PCR for transforming growth factor beta (TGF-beta1), insulin like growth factor-I (IGF-I) and fibroblast growth factors (FGF) mRNA expression. Electrostimulation of the cavernous nerves revealed a highly significant declining of the intracavernous pressure after 3 and 7 days. No significant recovery of erectile function was noted at 1 month. Histology showed degeneration of the dorsal nerve fibers in all experimental rats. There was little decrease in the bulk of intracavernous smooth muscle in the experimental rats euthanazed 7 and 30 days. NADPH diaphorase staining revealed a significant decrease in nitric oxide synthase (NOS) containing nerve fibers in the dorsal and intracavernosal nerves in all rats in the experimental group. Electron microscopy showed a variety of changes such as collapse of sinusoids, increased cell debris, fibroblast and myofibroblast loss, intracellular deposition of fat and collagen and fatty degeneration. RT-PCR revealed up-regulation of TGF-beta1 after 3 days but not after 7 days or 1 month. There is no significant difference in IGF-I or FGF expression between the experimental and control group. Bilateral ligation of internal iliac arteries produces a reliable animal model for traumatic arteriogenic ED. Further

  5. Sympathectomy alters bone architecture in adult growing rats.

    PubMed

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

    2008-08-15

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

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

    PubMed

    Fujinami, R S; Paterson, P Y

    1981-07-01

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

  7. 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

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

    PubMed

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

    2008-09-01

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

  9. 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

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

    PubMed

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

    2008-10-20

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

  11. 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...

  12. Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers.

    PubMed

    He, Z P; Tan, W Q; Tang, Y F; Zhang, H J; Feng, M F

    2004-04-01

    Oval cells, putative hepatic stem cells, could potentially provide a novel solution to the severe shortage of donor livers, because of their ability to proliferate and differentiate into functional hepatocytes. We have previously demonstrated that oval cells can be induced to differentiate into cells with morphologic, phenotypic, and functional characteristics of mature hepatocytes. In this study, we have established a new model combining ethionine treatment with partial hepatectomy to activate oval cells, then developed a procedure utilizing selective enzymatic digestion and density gradient centrifugation to isolate and purify such cells from heterogeneous liver cell population. We identified oval cells by their morphological characteristics and phenotypic properties, thereby providing definitive evidence of the presence of hepatic stem-like cells in adult rat livers. Viewed by transmission electron microscopy, they were small cells with ovoid nuclei, a high nucleus/cytoplasm ratio and few organelles, including mitochondria and endoplasmic reticulum. Flow cytometric assay showed that these cells highly expressed OV-6, cytokeratin-19 (CK-19) and albumin. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis displayed that the freshly isolated cells co-expressed albumin, cytokeratin-7 (CK-7) and CK-19 mRNA, indicating that they were essentially bipotential hepatic stem-like cells. Furthermore, we set up a culture system containing growth factors and a fibroblast feeder layer, to provide nourishment to these cells. Thus, we were able to culture them in vitro for more than 3 months, with the number of cells doubling 100 times. Gene expressions of albumin, CK-7 and CK-19 in the cells derived from the expanding colonies at day 95 were confirmed by RT-PCR analysis. These data suggested that the hepatic oval cells derived from adult rat livers possess a high potential to proliferate in vitro with a large increase in number, while maintaining the bipotential

  13. 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.

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

    PubMed Central

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

    2005-01-01

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

  15. 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

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

    PubMed

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

    2016-07-01

    Astrocytes are multitasking players in brain complexity, possessing several receptors and mechanisms to detect, participate and modulate neuronal communication. The functionality of astrocytes has been mainly unraveled through the study of primary astrocyte cultures, and recently our research group characterized a model of astrocyte cultures derived from adult Wistar rats. We, herein, aim to characterize other basal functions of these cells to explore the potential of this model for studying the adult brain. To characterize the astrocytic phenotype, we determined the presence of GFAP, GLAST and GLT 1 proteins in cells by immunofluorescence. Next, we determined the concentrations of thirteen amino acids, ATP, ADP, adenosine and calcium in astrocyte cultures, as well as the activities of Na(+)/K(+)-ATPase and acetylcholine esterase. Furthermore, we assessed the presence of the GABA transporter 1 (GAT 1) and cannabinoid receptor 1 (CB 1) in the astrocytes. Cells demonstrated the presence of glutamine, consistent with their role in the glutamate-glutamine cycle, as well as glutamate and D-serine, amino acids classically known to act as gliotransmitters. ATP was produced and released by the cells and ADP was consumed. Calcium levels were in agreement with those reported in the literature, as were the enzymatic activities measured. The presence of GAT 1 was detected, but the presence of CB 1 was not, suggesting a decreased neuroprotective capacity in adult astrocytes under in vitro conditions. Taken together, our results show cellular functionality regarding the astrocytic role in gliotransmission and neurotransmitter management since they are able to produce and release gliotransmitters and to modulate the cholinergic and GABAergic systems. PMID:26915106

  17. 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. PMID:26590368

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

    PubMed Central

    Carroll, Marilyn E.

    2010-01-01

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

  19. Folic acid in combination with adult neural stem cells for the treatment of spinal cord injury in rats

    PubMed Central

    Zhang, Chen; Shen, Lin

    2015-01-01

    Purpose: To observe the therapeutic effect of folic acid in combination with adult neural stem cells on spinal cord injury and to investigate the possible mechanism. Methods: A total of 120 Wistar rats were randomly assigned to six groups: normal, model, sham-surgery, folic acid injection, adult neural stem cell transplantation, and combination (folic acid injection + adult neural stem cells transplantation) groups. Morphology of neural stem cells was observed by inverted microscopy. Expression of CD105, CD45, CD44, and CD29 were detected by flow cytometry; expression of neuron-specific enolase and glial fibrillary acidic protein were determined by immunofluorescence. Motor coordination and integration capabilities were assessed using BBB scores; Morphology of spinal cord tissues was observed by hematoxylin-eosin staining and 5-bromodeoxyuridine immunohistochemistry. GDNF, BDNF and NT-3 expression in spinal cord tissues were determined by ELISA; while expression of the apoptosis-related proteins BCL-2, Bax and caspase-3 was detected using western blotting. Results: Flow cytometry showed that the isolated cells were positive for CD44 and CD29 and negative for CD105 and CD45. Combination treatment significantly improved the behavior of model rats with spinal cord injury, attenuated inflammatory reaction of spinal cord tissues, restored injured nerve cells, and increased expression of GDNF, BDNF and NT-3 in spinal cord tissues, up regulated BCL-2 expression, and down regulated Bax and caspase-3 expression. Conclusions: Folic acid in combination with adult neural stem cells significantly improved nerve function and plays a key role in maintaining microenvironment homeostasis in the neurons of rats with spinal cord injury. PMID:26379837

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

    PubMed Central

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

    2013-01-01

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

  1. 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

  2. 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

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

    PubMed

    Warszawski, D; Gorodischer, R; Kaplanski, J

    1978-01-01

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

  4. 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

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

    EPA Science Inventory

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

  6. 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...

  7. 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...

  8. 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…

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

    EPA Science Inventory

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

  10. 5,7-DIHYDROXYTRYPTAMINE INJECTIONS INCREASE GLIAL FIBRILLARY ACIDIC PROTEIN IN THE HYPOTHALAMUS OF ADULT RATS

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  12. 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...

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

    PubMed

    Haastert-Talini, Kirsten

    2012-01-01

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

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

    PubMed

    Oosthuizen, M K; Amrein, I

    2016-06-01

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

  15. Evaluation of a novel delayed-type hypersensitivity assay to Candida albicans in adult and neonatal rats.

    PubMed

    Thorn, Mitchell; Hudson, Adam W; Kreeger, John; Kawabe, Thomas T; Bowman, Christopher J; Collinge, Mark

    2015-01-01

    Delayed-type hypersensitivity (DTH) is a T-cell-mediated immune response that may be used for immunotoxicity testing in non-clinical species. However, in some cases DTH assays using T-dependent antigens may be confounded by the production of antibodies to the antigen. The authors have previously modified a DTH assay, initially validated in the mouse, for use in juvenile rats to assess the effect of immunosuppressive drugs on the developing rat immune system. The assay measures footpad swelling induced by subcutaneous footpad injection of Candida albicans (C. albicans) derived-chitosan in rats previously sensitized with C. albicans. Antibodies to chitosan are not produced in this model. However, considerable inter-animal variability inherent in the footpad swelling assay can make it difficult to precisely quantify the magnitude of the immune response and inhibition by immunosuppressants, particularly if complete suppression is not observed. This report describes the development of an ex vivo assay to assess DTH in rats using interferon (IFN)-γ production by splenocytes, obtained from rats sensitized with C. albicans, as the quantifiable measure of the DTH response. Adult and neonatal rats administered dexamethasone (DEX), a known immunosuppressant, exhibited immunosuppression as evidenced by a reduction in ex vivo IFNγ production from splenocytes challenged with C. albicans-derived chitosan. Current data indicate that the ex vivo based DTH assay is more sensitive than the conventional footpad swelling assay due to a lower background response and the ability to detect a response as early as post-natal day (PND) 12. The ex vivo based rat DTH assay offers a highly sensitive and quantitative alternative to the footpad swelling assay for the assessment of the immunotoxic potential of drugs. The increased sensitivity of the ex vivo DTH assay may be useful for identifying smaller changes in response to immunotoxic drugs, as well as detecting responses earlier in animal

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

    PubMed

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

    2016-06-01

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

  17. 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

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

    PubMed Central

    2009-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  20. Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat.

    PubMed

    Matthews, Keith; Robbins, Trevor W

    2003-01-01

    Depression is a major public health concern, representing one of the most significant causes of disability and morbidity. Despite significant advances in the definition of specific cognitive, emotional and neural dysfunctions that are associated with depression, there has been frustratingly little progress in the elucidation of plausible aetiological and pathophysiological mechanisms. The complex, multi-system dysfunctions of depressive illness do not lend themselves to hypothesis-driven, systematic manipulation in patients. For this reason, there is a need to develop valid and reliable models of affective psychopathology in laboratory animals. In this paper, we review briefly some of our previous work demonstrating that a specific periodic neonatal maternal separation procedure leads to a robust constellation of behavioural changes in the adult rat that resemble core aspects of human depressive psychopathology. We also present data from a study of the adult effects of the same manipulation on electrical intracranial self-stimulation behaviour. These data further support the hypothesis that it is possible to model vulnerability to anhedonia in the adult rat by manipulation of early experience. PMID:12732222

  1. Human Placenta-Derived Adherent Cell Treatment of Experimental Stroke Promotes Functional Recovery after Stroke in Young Adult and Older Rats

    PubMed Central

    Shehadah, Amjad; Chen, Jieli; Pal, Ajai; He, Shuyang; Zeitlin, Andrew; Cui, Xu; Zacharek, Alex; Cui, Yisheng; Roberts, Cynthia; Lu, Mei; Hariri, Robert; Chopp, Michael

    2014-01-01

    Background Human Placenta-Derived Adherent Cells (PDAC®) are a novel mesenchymal-like cell population derived from normal human placental tissue. PDA-001 is a clinical formulation of PDAC® developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in young adult (2–3 month old) and older rats (10–12 months old). Methods To evaluate efficacy and determine the optimal number of transplanted cells, young adult Wistar rats were subjected to MCAo and treated 1 day post MCAo with 1×106, 4×106 or 8×106 PDA-001 cells (i.v.), vehicle or cell control. 4×106 or 8×106 PDA-001 cells were also tested in older rats after MCAo. Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS) and foot-fault test. Young adult rats were sacrificed 56 days after MCAo, older rats were sacrificed 29 days after MCAo, and lesion volumes were measured using H&E. Immunohistochemical stainings for bromodeoxyuridine (BrdU) and von Willebrand Factor (vWF), and synaptophysin were performed. Results In young adult rats, treatment with 4×106 PDA-001 cells significantly improved functional outcome after stroke (p<0.05). In older rats, significant functional improvement was observed with PDA-001 cell therapy in both of the 4×106 and 8×106 treatment groups. Functional benefits in young adult and older rats were associated with significant increases in the number of BrdU immunoreactive endothelial cells, vascular density and perimeter in the ischemic brain, as well as significantly increased synaptophysin expression in the ischemic border zone (p<0.05). Conclusion PDA-001 treatment significantly improved functional outcome after stroke in both young adult and older rats. The neurorestorative effects induced by PDA-001 treatment may be related to increased vascular density and

  2. 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

  3. 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…

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

    PubMed

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

    2011-10-24

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

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

    PubMed

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

    1997-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. The rat choledochojejunostomy model for microsurgical training

    PubMed Central

    Lee, Jun Suh

    2016-01-01

    Purpose The feasibility of a rat choledochojejunostomy (CJ) training model was investigated, as an introductory model to microsurgery for general surgeons. Methods Roux-en-Y CJ was performed on 20 rats. Interrupted 10-0 prolene sutures were used to perform CJ. The animals were observed for 7 days and sacrificed and examined. Results The rats were divided into 2 groups of 10 based on surgical order. The CJ time showed a significant decrease from 36.2 ± 5.6 minutes in group 1 to 29.4 ± 5.7 minutes in group 2 (P = 0.015). The bile leakage rate was 40% in group 1 and 10% in group 2. The survival time was 5.4 ± 2.2 days in group 1 and 7 days in group 2 (P = 0.049). Conclusion The rat CJ training model is a feasible introductory model for general surgeons with no previous experience in microsurgery. PMID:27186568

  10. 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.

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

    PubMed Central

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

    2016-01-01

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

  12. 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.

  13. Multivariate models of adult Pacific salmon returns.

    PubMed

    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

  14. 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

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

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

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

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

    SciTech Connect

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

    1980-12-01

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

  19. Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.

    PubMed

    Turner, K J; Morley, M; Atanassova, N; Swanston, I D; Sharpe, R M

    2000-02-01

    The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively

  20. Different effects of prenatal stress on ERK2/CREB/Bcl-2 expression in the hippocampus and the prefrontal cortex of adult offspring rats.

    PubMed

    Zhu, Zeen; Sun, Hongli; Gong, Xiaojie; Li, Hui

    2016-05-25

    It has become increasingly evident that prenatal stress and its psychological and physiological concomitants are associated with the pathophysiology of mood disorders. However, the mechanisms underlying the prenatal stress-induced offspring's anxiety disorders remain unknown. We recently reported that prenatal stress enhanced anxiety-like behavior in adult offspring rat, and involved N-methyl-D-aspartate receptor subunits, including NR1 and NR2A. In the present research, using the same prenatal stress model, we measured the ERK2/CREB/Bcl-2 mRNA levels by real-time PCR. Our findings indicated that prenatal stress decreased ERK2 and CREB mRNA levels in the hippocampus and the prefrontal cortex and Bcl-2 mRNA levels in the hippocampus of offspring rat. The results showed that the abnormal ERK2, CREB, and Bcl-2 mRNA levels may be involved in the anxiety-like behavior of adult rats with prenatal stress. PMID:27096215

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

    PubMed

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

    2011-10-10

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

  4. Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

    PubMed

    Winston, John H; Sarna, Sushil K

    2016-07-01

    Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats. PMID:27151940

  5. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-11-10

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

  8. 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.

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

    PubMed

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

    2015-12-01

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

  10. Testosterone influences spatial strategy preferences among adult male rats

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    1985-01-01

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

  12. 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.

  13. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    Whiting, S J; Whitney, H L

    1987-07-01

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

  19. Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction.

    PubMed

    Noonan, Michele A; Bulin, Sarah E; Fuller, Dwain C; Eisch, Amelia J

    2010-01-01

    Drugs of abuse dynamically regulate adult neurogenesis, which appears important for some types of learning and memory. Interestingly, a major site of adult neurogenesis, the hippocampus, is important in the formation of drug-context associations and in the mediation of drug-taking and drug-seeking behaviors in animal models of addiction. Correlative evidence suggests an inverse relationship between hippocampal neurogenesis and drug-taking or drug-seeking behaviors, but the lack of a causative link has made the relationship between adult-generated neurons and addiction unclear. We used rat intravenous cocaine self-administration in rodents, a clinically relevant animal model of addiction, to test the hypothesis that suppression of adult hippocampal neurogenesis enhances vulnerability to addiction and relapse. Suppression of adult hippocampal neurogenesis via cranial irradiation before drug-taking significantly increased cocaine self-administration on both fixed-ratio and progressive-ratio schedules, as well as induced a vertical shift in the dose-response curve. This was not a general enhancement of learning, motivation, or locomotion, because sucrose self-administration and locomotor activity were unchanged in irradiated rats. Suppression of adult hippocampal neurogenesis after drug-taking significantly enhanced resistance to extinction of drug-seeking behavior. These studies identify reduced adult hippocampal neurogenesis as a novel risk factor for addiction-related behaviors in an animal model of cocaine addiction. Furthermore, they suggest that therapeutics to specifically increase or stabilize adult hippocampal neurogenesis could aid in preventing initial addiction as well as future relapse. PMID:20053911

  20. Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction

    PubMed Central

    Noonan, Michele A.; Bulin, Sarah; Fuller, Dwain C.; Eisch, Amelia J.

    2010-01-01

    Drugs of abuse dynamically regulate adult neurogenesis, which appears important for some types of learning and memory. Interestingly, a major site of adult neurogenesis - the hippocampus - is important in the formation of drug-context associations and in the mediation of drug-taking and drug-seeking behaviors in animal models of addiction. Correlative evidence suggests an inverse relationship between hippocampal neurogenesis and drug-taking or drug-seeking behaviors, but the lack of a causative link has made the relationship between adult-generated neurons and addiction unclear. We used rat i.v. cocaine self-administration in rodents, a clinicall-relevant animal model of addiction, to test the hypothesis that suppression of adult hippocampal neurogenesis enhances vulnerability to addiction and relapse. Suppression of adult hippocampal neurogenesis via cranial irradiation before drug-taking significantly increased cocaine self-administration on both fixed-ratio and progressive-ratio schedules, as well as induced a vertical shift in the dose-response curve. This was not a general enhancement of learning, motivation or locomotion, as sucrose self-administration and locomotor activity were unchanged in irradiated rats. Suppression of adult hippocampal neurogenesis after drug-taking significantly enhanced resistance to extinction of drug-seeking behavior. These studies identify reduced adult hippocampal neurogenesis as a novel risk factor for addiction-related behaviors in an animal model of cocaine addiction. Further, they suggest that therapeutics to specifically increase or stabilize adult hippocampal neurogenesis could aid in preventing initial addiction as well as future relapse. PMID:20053911

  1. 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.

  2. A Method for the Isolation and Culture of Adult Rat Retinal Pigment Epithelial (RPE) Cells to Study Retinal Diseases

    PubMed Central

    Heller, Janosch P.; Kwok, Jessica C. F.; Vecino, Elena; Martin, Keith R.; Fawcett, James W.

    2015-01-01

    Diseases such as age-related macular degeneration (AMD) affect the retinal pigment epithelium (RPE) and lead to the death of the epithelial cells and ultimately blindness. RPE transplantation is currently a major focus of eye research and clinical trials using human stem cell-derived RPE cells are ongoing. However, it remains to be established to which extent the source of RPE cells for transplantation affects their therapeutic efficacy and this needs to be explored in animal models. Autotransplantation of RPE cells has attractions as a therapy, but existing protocols to isolate adult RPE cells from rodents are technically difficult, time-consuming, have a low yield and are not optimized for long-term cell culturing. Here, we report a newly devised protocol which facilitates reliable and simple isolation and culture of RPE cells from adult rats. Incubation of a whole rat eyeball in 20 U/ml papain solution for 50 min yielded 4 × 104 viable RPE cells. These cells were hexagonal and pigmented upon culture. Using immunostaining, we demonstrated that the cells expressed RPE cell-specific marker proteins including cytokeratin 18 and RPE65, similar to RPE cells in vivo. Additionally, the cells were able to produce and secrete Bruch’s membrane matrix components similar to in vivo situation. Similarly, the cultured RPE cells adhered to isolated Bruch’s membrane as has previously been reported. Therefore, the protocol described in this article provides an efficient method for the rapid and easy isolation of high quantities of adult rat RPE cells. This provides a reliable platform for studying the therapeutic targets, testing the effects of drugs in a preclinical setup and to perform in vitro and in vivo transplantation experiments to study retinal diseases. PMID:26635529

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

    PubMed

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

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders. PMID:26383033

  4. 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

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

    PubMed

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

    2010-07-01

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

  6. Rat Model of Parkes Weber Syndrome.

    PubMed

    Bojakowski, Krzysztof; Janusz, Gabriela; Grabowska, Iwona; Zegrocka-Stendel, Oliwia; Surowiecka-Pastewka, Agnieszka; Kowalewska, Magdalena; Maciejko, Dorota; Koziak, Katarzyna

    2015-01-01

    The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment. PMID:26217941

  7. Rat Model of Parkes Weber Syndrome

    PubMed Central

    Bojakowski, Krzysztof; Janusz, Gabriela; Grabowska, Iwona; Zegrocka-Stendel, Oliwia; Surowiecka-Pastewka, Agnieszka; Kowalewska, Magdalena; Maciejko, Dorota; Koziak, Katarzyna

    2015-01-01

    The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment. PMID:26217941

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  10. 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,...

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

    PubMed

    Visavadiya, Nishant P; Springer, Joe E

    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

  12. Effect of estrogen receptor-subtype-specific ligands on fertility in adult male rats.

    PubMed

    Dumasia, Kushaan; Kumar, Anita; Kadam, Leena; Balasinor, N H

    2015-06-01

    Maintenance of normal male fertility relies on the process of spermatogenesis which is under complex endocrine control by mechanisms involving gonadotropin and steroid hormones. Although testosterone is the primary sex steroid in males, estrogen is locally produced in the testis and plays a very crucial role in male fertility. This is evident from presence of both the estrogen receptors alpha (ERα) and beta (ERβ) in the testis and their absence, as in the case of knockout mice models, leads to sterility. The present study was undertaken to understand individual roles of the two ERs in spermatogenesis and their direct contribution towards the maintenance of male fertility using receptor-subtype-specific ligands. Administration of ERα and β agonists to adult male rats for 60 days results in a significant decrease in fertility, mainly due to an increase in pre- and post-implantation loss and a concomitant decrease in litter size and sperm counts. Our results indicate that ERα is mainly involved in negative feedback regulation of gonadotropin hormones, whereas both ERs are involved in regulation of prolactin and testosterone production. Histological examinations of the testis reveal that ERβ could be involved in the process of spermiation since many failed spermatids were observed in stages IX-XI following ERβ agonist treatment. Our results indicate that overactivation of estrogen signaling through either of its receptors can have detrimental effects on the fertility parameters and that the two ERs have both overlapping and distinct roles in maintenance of male fertility. PMID:25869617

  13. Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats.

    PubMed

    Abrial, Erika; Etievant, Adeline; Bétry, Cécile; Scarna, Hélène; Lucas, Guillaume; Haddjeri, Nasser; Lambás-Señas, Laura

    2013-06-01

    The neurobiological mechanisms underlying the pathophysiology and therapeutics of bipolar disorder are still unknown. In recent years, protein kinase C (PKC) has emerged as a potential key player in mania. To further investigate the role of this signaling system in mood regulation, we examined the effects of PKC modulators in behavioral tests modeling several facets of bipolar disorder and in adult hippocampal cell proliferation in rats. Our results showed that a single injection of the PKC inhibitors tamoxifen (80 mg/kg, i.p.) and chelerythrine (3 mg/kg, s.c.) attenuated amphetamine-induced hyperlocomotion and decreased risk-taking behavior, supporting the efficacy of PKC blockade in acute mania. Moreover, chronic exposure to tamoxifen (10 mg/kg/day, i.p., for 14 days) or chelerythrine (0.3 mg/kg/day, s.c., for 14 days) caused depressive-like behavior in the forced swim test, and resulted in a reduction of cell proliferation in the dentate gyrus of the hippocampus. Finally, we showed that, contrary to the PKC inhibitors, the PKC activator phorbol 12-myristate 13-acetate (PMA) enhanced risk-taking behavior and induced an antidepressant-like effect. Taken together, these findings support the involvement of PKC in regulating opposite facets of bipolar disorder, and emphasize a major role for PKC in this disease. PMID:23228462

  14. Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes.

    PubMed

    Fields, Laura A; Koschinski, Andreas; Zaccolo, Manuela

    2016-07-01

    In the heart compartmentalisation of cAMP/protein kinase A (PKA) signalling is necessary to achieve a specific functional outcome in response to different hormonal stimuli. Chronic exposure to catecholamines is known to be detrimental to the heart and disrupted compartmentalisation of cAMP signalling has been associated to heart disease. However, in most cases it remains unclear whether altered local cAMP signalling is an adaptive response, a consequence of the disease or whether it contributes to the pathogenetic process. We have previously demonstrated that isoforms of PKA expressed in cardiac myocytes, PKA-I and PKA-II, localise to different subcellular compartments and are selectively activated by spatially confined pools of cAMP, resulting in phosphorylation of distinct downstream targets. Here we investigate cAMP signalling in an in vitro model of hypertrophy in primary adult rat ventricular myocytes. By using a real time imaging approach and targeted reporters we find that that sustained exposure to catecholamines can directly affect cAMP/PKA compartmentalisation. This appears to involve a complex mechanism including both changes in the subcellular localisation of individual phosphodiesterase (PDE) isoforms as well as the relocalisation of PKA isoforms. As a result, the preferential coupling of PKA subsets with different PDEs is altered resulting in a significant difference in the level of cAMP the kinase is exposed to, with potential impact on phosphorylation of downstream targets. PMID:26475678

  15. 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

  16. The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

    PubMed Central

    Steinberg, Rebecca M.; Juenger, Thomas E.; Gore, Andrea C.

    2009-01-01

    Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the Sprague-Dawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female’s likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. PMID:17274994

  17. Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

    PubMed

    Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

    2002-04-01

    Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities. PMID:11893582

  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. PMID:26836141

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

    PubMed Central

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

    2013-01-01

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

  20. 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

  1. Investigation of infectivity of neonates and adults from different rat strains to Toxoplasma gondii Prugniaud shows both variation which correlates with iNOS and Arginase-1 activity and increased susceptibility of neonates to infection.

    PubMed

    Gao, Jiang-Mei; Yi, Si-Qi; Wu, Ming-Shui; Geng, Guo-Qing; Shen, Ji-Long; Lu, Fang-Li; Hide, Geoff; Lai, De-Hua; Lun, Zhao-Rong

    2015-02-01

    Mouse models differ considerably from humans with regard to clinical symptoms of toxoplasmosis caused by Toxoplasma gondii and, by comparison, the rat model is more representative of this disease in humans. In the present study, we found that different strains of adult and newborn rats (Lewis, Wistar, Sprague Dawley, Brown Norway and Fischer 344) exhibited remarkable variation in the number of brain cysts following inoculation with the T.gondii Prugniaud strain. In adult rats, large numbers of cysts (1231 ± 165.6) were observed in Fischer 344, but none in the other four. This situation was different in newborn rats aged from 5 to 20 days old. All Fischer 344 and Brown Norway newborns were cyst-positive while cyst-positive infection in Sprague Dawley neonates ranged from 54.5% to 60% depending on their age at infection. In Wistar and Lewis rat neonates, however, cyst-positivity rates of 0-42.9% and 0-25% were found respectively. To investigate whether rat strain differences in infectivity could be related to inherent strain and genetic differences in the host immune response, we correlated our data with previously reported strain differences in iNOS/Arginase ratio in adult rats and found them to be linked. These results show that interactions between host genetic background and age of rat influence T.gondii infection. PMID:25541383

  2. A mathematical model of adult subventricular neurogenesis

    PubMed Central

    Ashbourn, J. M. A.; Miller, J. J.; Reumers, V.; Baekelandt, V.; Geris, L.

    2012-01-01

    Neurogenesis has been the subject of active research in recent years and many authors have explored the phenomenology of the process, its regulation and its purported purpose. Recent developments in bioluminescent imaging (BLI) allow direct in vivo imaging of neurogenesis, and in order to interpret the experimental results, mathematical models are necessary. This study proposes such a mathematical model that describes adult mammalian neurogenesis occurring in the subventricular zone and the subsequent migration of cells through the rostral migratory stream to the olfactory bulb (OB). This model assumes that a single chemoattractant is responsible for cell migration, secreted both by the OB and in an endocrine fashion by the cells involved in neurogenesis. The solutions to the system of partial differential equations are compared with the physiological rodent process, as previously documented in the literature and quantified through the use of BLI, and a parameter space is described, the corresponding solution to which matches that of the rodent model. A sensitivity analysis shows that this parameter space is stable to perturbation and furthermore that the system as a whole is sloppy. A large number of parameter sets are stochastically generated, and it is found that parameter spaces corresponding to physiologically plausible solutions generally obey constraints similar to the conditions reported in vivo. This further corroborates the model and its underlying assumptions based on the current understanding of the investigated phenomenon. Concomitantly, this leaves room for further quantitative predictions pertinent to the design of future proposed experiments. PMID:22572029

  3. Older Adults in Child Care: A Job-Training Model.

    ERIC Educational Resources Information Center

    Ward, Christopher R.; Smith, Thomas B.

    Recognizing the increasing demand for older adults to work as child care employees, this manual presents the Generations Together model for training older adults at the community college level to work in child care settings. The manual describes the steps necessary to implement a community-college-based, older-adult child care employment training…

  4. 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…

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

    PubMed Central

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

    1997-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2015-08-01

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

  9. 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.

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

    PubMed

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

    2012-04-01

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

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

    PubMed

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

    2011-09-01

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

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

    PubMed

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

    1982-11-01

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

  13. Actin related protein complex subunit 1b controls sperm release, barrier integrity and cell division during adult rat spermatogenesis.

    PubMed

    Kumar, Anita; Dumasia, Kushaan; Deshpande, Sharvari; Gaonkar, Reshma; Balasinor, N H

    2016-08-01

    Actin remodeling is a vital process for signaling, movement and survival in all cells. In the testes, extensive actin reorganization occurs at spermatid-Sertoli cell junctions during sperm release (spermiation) and at inter Sertoli cell junctions during restructuring of the blood testis barrier (BTB). During spermiation, tubulobulbar complexes (TBCs), rich in branched actin networks, ensure recycling of spermatid-Sertoli cell junctional molecules. Similar recycling occurs during BTB restructuring around the same time as spermiation occurs. Actin related protein 2/3 complex is an essential actin nucleation and branching protein. One of its subunits, Arpc1b, was earlier found to be down-regulated in an estrogen-induced rat model of spermiation failure. Also, Arpc1b was found to be estrogen responsive through estrogen receptor beta in seminiferous tubule culture. Here, knockdown of Arpc1b by siRNA in adult rat testis led to defects in spermiation caused by failure in TBC formation. Knockdown also compromised BTB integrity and caused polarity defects of mature spermatids. Apart from these effects pertaining to Sertoli cells, Arpc1b reduction perturbed ability of germ cells to enter G2/M phase thus hindering cell division. In summary, Arpc1b, an estrogen responsive gene, is a regulator of spermiation, mature spermatid polarity, BTB integrity and cell division during adult spermatogenesis. PMID:27113856

  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. PMID:26421020

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

    SciTech Connect

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

    1993-01-01

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

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

    SciTech Connect

    Duckett, S.

    1982-11-01

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

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

    PubMed

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

    2016-05-13

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. Rat injury model of docetaxel extravasation

    PubMed Central

    ZHU, JING-JING; FU, JIAN-FEI; YANG, JIAO; HU, BING; ZHANG, HUI; YU, JIAN-HUA

    2014-01-01

    Docetaxel is a novel type of chemotherapy drug that actively treats a number of malignant tumors. The aim of the present study was to explore the severity and natural course of tissue damage induced by docetaxel extravasation and to confirm the vesicant potential of docetaxel. Rats were selected for the establishment of the ulcer model. Different volumes and concentrations were explored to induce the skin ulcer and to confirm the optimum rational injection model. The natural course of tissue injury and pathological changes produced by docetaxel extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml volume and a 6 mg/ml concentration were the optimum rational injection model for the induction of the skin ulcer. The docetaxel extravasation induced local tissue necrosis, followed by granuloma formation and hyperpigmentation or scar formation. The severity of the injury depended on the concentration of the extravasation used in the rat model. The injury occurred on the first day following extravasation and lasted 4–6 weeks. The damage from docetaxel was weaker than vinorelbine in association with the depth and extension of necrosis. In conclusion, docetaxel extravasation can induce tissue necrosis. However, the severity of necrosis was weaker than that of vinorelbine. Docetaxel has superficial vesicant properties. PMID:25054005

  3. 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

  4. Comprehensive Locomotor Outcomes Correlate to Hyperacute Diffusion Tensor Measures After Spinal Cord Injury in the Adult Rat

    PubMed Central

    Kim, Joong; Song, Sheng-Kwei; Burke, Darlene A.; Magnuson, David S. K.

    2012-01-01

    In adult rats, locomotor deficits following a contusive thoracic spinal cord injury (SCI) are caused primarily by white matter loss/dysfunction at the epicenter. This loss/dysfunction decreases descending input from the brain and cervical spinal cord, and decreases ascending signals in long propriospinal, spinocerebellar and somatosensory pathways, among many others. Predicting the long-term functional consequences of a contusive injury acutely, without knowledge of the injury severity is difficult due to the temporary flaccid paralysis and loss of reflexes that accompanies spinal shock. It is now well known that recovery of high quality hindlimb stepping requires only 12-15% spared white matter at the epicenter, but that forelimb-hindlimb coordination and precision stepping (grid or horizontal ladder) requires substantially more trans-contusion communication. In order to translate our understanding of the neural substrates for functional recovery in the rat to the clinical arena, common outcome measures and imaging modalities are required. In the current study we furthered the exploration of one of these approaches, diffusion tensor magnetic resonance imaging (DTI), a technique now used commonly to image the brain in clinical research but rarely used diagnostically or prognostically for spinal cord injury. In the adult rat model of SCI, we found that hyper-acute (<3 hours post-injury) DTI of the lateral and ventral white matter at the injury epicenter was predictive of both electrophysiological and behavioral (locomotor) recovery at 4 weeks post-injury, despite the presence of flaccid paralysis/spinal shock. Regions of white matter with a minimum axial diffusivity of 1.5μm2/ms at 3 hours were able to conduct action potentials at 4 weeks, and axial diffusivity within the lateral funiculus was highly predictive of locomotor function at 4 weeks. These observations suggest that acute DTI should be useful to provide functional predictions for spared white matter

  5. Evidence that the periaqueductal gray matter mediates the facilitation of panic-like reactions in neonatally-isolated adult rats.

    PubMed

    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

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

    PubMed

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

    2002-12-01

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

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

    PubMed

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

    1999-06-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    1982-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1997-08-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    1997-01-01

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

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

    PubMed

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

    2013-04-15

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

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

    PubMed Central

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

    2013-01-01

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

  17. 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

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

    PubMed Central

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

    2010-01-01

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

  19. 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

  20. 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.

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

    PubMed

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

    2013-06-01

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

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

    PubMed

    Mabrouk, Aymen; Ben Cheikh, Hassen

    2016-06-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2010-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Shekarforoush, Shahnaz; Ebrahimi, Zahra; Hoseini, Maryam

    2015-01-01

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

  8. Differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

    PubMed

    Tong, Ling-Ling; Ding, You-Quan; Jing, Hong-Bo; Li, Xuan-Yang; Qi, Jian-Guo

    2015-05-01

    Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aβ and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush. PMID:25830493

  9. 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. PMID:26730408

  10. Hematopoietic bone marrow cells participate in endothelial, but not epithelial or mesenchymal cell renewal in adult rats

    PubMed Central

    Odörfer, Kathrin I; Egerbacher, Monika; Unger, Nina J; Weber, Karin; Jamnig, Angelika; Lepperdinger, Günter; Kleiter, Miriam; Sandgren, Eric P; Erben, Reinhold G

    2011-01-01

    The extent to which bone marrow (BM) contributes to physiological cell renewal is still controversial. Using the marker human placental alkaline phosphatase (ALPP) which can readily be detected in paraffin and plastic sections by histochemistry or immunohistochemistry, and in ultrathin sections by electron microscopy after pre-embedding staining, we examined the role of endogenous BM in physiological cell renewal by analysing tissues from lethally irradiated wild-type inbred Fischer 344 (F344) rats transplanted (BMT) with unfractionated BM from ALPP-transgenic F344 rats ubiquitously expressing the marker. Histochemical, immunohistochemical and immunoelectron microscopic analysis showed that the proportion of ALPP+ capillary endothelial cells (EC) profoundly increased from 1 until 6 months after BMT in all organs except brain and adrenal medulla. In contrast, pericytes and EC in large blood vessels were ALPP–. Epithelial cells in kidney, liver, pancreas, intestine and brain were recipient-derived at all time-points. Similarly, osteoblasts, chondrocytes, striated muscle and smooth muscle cells were exclusively of recipient origin. The lack of mesenchymal BM-derived cells in peripheral tissues prompted us to examine whether BMT resulted in engraftment of mesenchymal precursors. Four weeks after BMT, all haematopoietic BM cells were of donor origin by flow cytometric analysis, whereas isolation of BM mesenchymal stem cells (MSC) failed to show engraftment of donor MSC. In conclusion, our data show that BM is an important source of physiological renewal of EC in adult rats, but raise doubt whether reconstituted irradiated rats are an apt model for BM-derived regeneration of mesenchymal cells in peripheral tissues. PMID:21091631

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

    PubMed Central

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

    1999-01-01

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

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

    PubMed

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

    1999-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2013-08-01

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

  17. 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

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

    PubMed

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

    2015-01-01

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

  19. 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

  20. Neonatal Androgenization Exacerbates Alcohol-Induced Liver Injury in Adult Rats, an Effect Abrogated by Estrogen

    PubMed Central

    Ellefson, Whitney M.; Lakner, Ashley M.; Hamilton, Alicia; McKillop, Iain H.; Bonkovsky, Herbert L.; Steuerwald, Nury M.; Huet, Yvette M.; Schrum, Laura W.

    2011-01-01

    Alcoholic liver disease (ALD) affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2) and ethanol metabolizing enzymes (cytochrome P450, CYP450) are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl), androgenized females (Andro) and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood. PMID:22206017

  1. Differential roles of estrogen receptors, ESR1 and ESR2, in adult rat spermatogenesis.

    PubMed

    Dumasia, Kushaan; Kumar, Anita; Deshpande, Sharvari; Sonawane, Shobha; Balasinor, N H

    2016-06-15

    Estrogens, through their receptors, play an important role in regulation of spermatogenesis. However, the precise role of the estrogen receptors (ESR1 and ESR2) has been difficult to determine as in vivo estradiol treatment would signal through both the ESRs. Hence we had developed in vivo selective ESR agonist administration models in adult male rats to decipher the individual roles of the ESRs. Treatment with both ESR1 and ESR2 agonists decreased sperm counts after 60 days of treatment. The present study aimed to delineate the precise causes of decreased sperm counts following treatment with the two ESR agonists. Treatment with ESR1 agonist causes an arrest in differentiation of round spermatids into elongated spermatids, mainly due to down-regulation of genes involved in spermiogenesis. ESR2 agonist administration reduces sperm counts due to spermiation failure and spermatocyte apoptosis. Spermiation failure observed is due to defects in tubulobulbar complex formation because of decrease in expression of genes involved in actin remodelling. The increase in spermatocyte apoptosis could be due to increase in oxidative stress and decrease in transcripts of anti-apoptotic genes. Our results suggest that the two ESRs regulate distinct aspects of spermatogenesis. ESR1 is mainly involved with regulation of spermiogenesis, while ESR2 regulates spermatocyte apoptosis and spermiation. Activation of estrogen signaling through either of the receptors can affect their respective processes during spermatogenesis and lead to low sperm output. Since many environmental estrogens can bind to the two ESRs with different affinities, these observations can be useful in understanding their potential effects on spermatogenesis. PMID:27004961

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2013-04-01

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

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

    PubMed

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

    2013-01-01

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

  9. Rat Carotid Artery Balloon Injury Model

    PubMed Central

    Tulis, David Anthony

    2010-01-01

    i. Summary Numerous and diverse experimental animal models have been used over the years to examine reactions to various forms of blood vessel disease and/or injury across species and in multiple vascular beds in a cumulative effort to relate these findings to the human condition. In this context, the rat carotid artery balloon injury model is highly characterized and commonly used for investigating gross morphological, cellular, biochemical, and molecular components of the response to experimentally-induced arterial injury. The mechanical damage caused by the balloon catheter completely removes the intimal endothelial lining and creates a distending mural injury in the operated vessel. This elicits a reproducible remodeling response characterized by vascular smooth muscle cell (SMC) mitogenesis and migration (via phenotypic switching), SMC apoptosis, partial vascular endothelial cell regeneration, enhanced matrix synthesis, and establishment of an invasive neointima in time-dependent fashion. This multi-factorial process allows for investigation of these many important pathophysiological processes and can serve as a valuable “proof-of-concept” tool to verify and substantiate in vitro results; however, inherent anatomical and adaptive constraints of this in vivo model ration comparison to the diseased human system (see Note 1). In this chapter, brief overview of the materials needed and the methodologies commonly employed for successful routine performance of this important experimental animal model will be provided. Individual sub-sections will cover animal care and handling, pre- and post-operative procedures, and the surgery proper. Protocols for histopathology and morphometry and procedures for data management and interpretation pertinent to the rat carotid artery balloon injury model will be discussed in Chapter __ of this series. Notes will conclude with important caveats, limitations, and considerations for practical use of this technique. PMID:18287662

  10. 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

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

    PubMed

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

    2012-06-01

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

  12. Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access Conditions

    PubMed Central

    Vetter, Courtney S.; Doremus-Fitzwater, Tamara L.; Spear, Linda P.

    2007-01-01

    Background Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague–Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods Adolescent [postnatal day (P)27–28] and adult (P69–70) male Sprague–Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing–containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28–39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or

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

    PubMed

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

    2014-04-01

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

  14. G-Protein Modulation of Voltage-Gated Ca2+ Channels from Isolated Adult Rat Superior Cervical Ganglion Neurons.

    PubMed

    Lu, Van B; Ikeda, Stephen R

    2016-01-01

    Sympathetic neurons isolated from adult rat superior cervical ganglia (SCG) are a well-established model to study G-protein modulation of voltage-gated Ca(2+) channels (VGCCs). SCG neurons can be easily dissociated and are amendable to heterologous expression of genes, including genetic tools to study G-protein signaling pathways, within a time frame to maintain good spatial voltage-clamp control of membrane potential during electrophysiological recordings (8-36 h postdissociation). This protocol focuses on examining G-protein modulation of VGCCs; however, the procedures and experimental setup for acute application of agonists can be applied to study modulation of other ion channels (e.g., M-current, G-protein-coupled inwardly rectifying K(+) channels). We also discuss some common sources of artifacts that can arise during acute drug application onto dissociated neurons, which can mislead interpretation of results. PMID:27140920

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

    PubMed Central

    Shao, Chunhong; Zucker, Irving H.

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD

    PubMed Central

    Natsheh, Joman Y.; Shiflett, Michael W.

    2015-01-01

    Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75–P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar–Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action–outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively. PMID:26635568

  20. The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD.

    PubMed

    Natsheh, Joman Y; Shiflett, Michael W

    2015-01-01

    Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar-Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively. PMID:26635568

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2015-04-01

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

  4. 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.

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    2014-05-01

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

  7. Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats.

    PubMed

    Wang, Fen; Zeng, Xianzhong; Zhu, Yangbo; Ning, Dan; Liu, Junxia; Liu, Chunlei; Jia, Xuemei; Zhu, Defa

    2015-02-01

    A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a significant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism. PMID:25371181

  8. Early antipsychotic treatment in childhood/adolescent period has long-term effects on depressive-like, anxiety-like and locomotor behaviours in adult rats.

    PubMed

    De Santis, Michael; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2016-02-01

    Childhood/adolescent antipsychotic drug (APD) use is exponentially increasing worldwide, despite limited knowledge of the long-term effects of early APD treatment. Whilst investigations have found that early treatment has resulted in some alterations to dopamine and serotonin neurotransmission systems (essential to APD efficacy), there have only been limited studies into potential long-term behavioural changes. This study, using an animal model for childhood/adolescent APD treatment, investigated the long-term effects of aripiprazole, olanzapine and risperidone on adult behaviours of male and female rats. Open-field/holeboard, elevated plus maze (EPM), social interaction and forced swim (FS) tests were then conducted in adult rats. Our results indicated that in the male cohort, early risperidone and olanzapine treatment elicited long-term hyper-locomotor effects (open-field/holeboard and FS tests), whilst a decrease in depressive-like behaviour (in FS test) was observed in response to olanzapine treatment. Furthermore, anxiolytic-like behaviours were found following testing in the open-field/holeboard and EPM in response to all three drug treatments. Effects in the female cohort, however, were to a far lesser extent, with behavioural attributes indicative of an increased depressive-like behaviour and hypo-locomotor activity exhibited in the FS test following early risperidone and olanzapine treatment. These results suggest that various APDs have different long-term effects on the behaviours of adult rats. PMID:26577063

  9. 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. PMID:24953757

  10. Radical Reeducation: Alcoholics Anonymous as a Model in Adult Education.

    ERIC Educational Resources Information Center

    Crossman, Lenard H.

    1980-01-01

    The peer self-help group approach used by Alcoholics Anonymous can be a model for other types of adult learning. The group's power, solidarity, experience sharing, and values clarification can provide positive social and educational experiences to others such as the chronically unemployed, illiterate adults, and high school dropouts. (SK)

  11. Adult Community Education: A Model for Regional Policy Development.

    ERIC Educational Resources Information Center

    Jones, Peter

    1998-01-01

    The adult community education (ACE) sector in the state of Victoria provides an example of best practice in regional rural policy in Australia that may serve as a model for other areas of government effort. In 1997, 309,000 Victorians enrolled in adult and community education courses, such as business and technical skills development, literacy and…

  12. A MODEL INFORMATION SYSTEM FOR THE ADULT EDUCATION PROFESSION.

    ERIC Educational Resources Information Center

    DECROW, ROGER

    A MODEL OF INFORMATION SERVICES FOR THE ADULT EDUCATION PROFESSION PROVIDES FOR--(1) ACCESS TO THE LITERATURE THROUGH BIBLIOGRAPHIES, REVIEWS, AND MECHANIZED RETRIEVAL, (2) PHYSICAL ACCESS (MAINLY IN MICROFORM), (3) SPECIALIZED INFORMATION SERVICES LINKED WITH ONE ANOTHER AND THE ERIC CLEARINGHOUSE ON ADULT EDUCATION, (4) COORDINATION, RESEARCH,…

  13. Building a Data Based Model for Senior Adult Basic Education.

    ERIC Educational Resources Information Center

    Courtenay, Bradley C.; And Others

    Research shows that developing a curriculum model for senior adult education requires consideration of at least four important factors: (1) the heterogeneous nature of the senior adult population; (2) their specific information and interest needs; (3) the specific nature of the learning activities; and (4) the specific barriers and facilitators…

  14. Infant Imitation from Televised Peer and Adult Models

    ERIC Educational Resources Information Center

    Seehagen, Sabine; Herbert, Jane S.

    2011-01-01

    Developmental changes in learning from peers and adults during the second year of life were assessed using an imitation paradigm. Independent groups of 15- and 24-month-old infants watched a prerecorded video of an unfamiliar child or adult model demonstrating a series of actions with objects. When learning was assessed immediately, 15-month-old…

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2016-04-01

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

  1. 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.

  2. Comparison of DEXA and QMR for Assessing Fat and Lean Body Mass in Adult Rats

    PubMed Central

    Miller, Colette N.; Kauffman, Tricia G.; Cooney, Paula T.; Ramseur, Keshia R.; Brown, Lynda M.

    2011-01-01

    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. PMID:21167190

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2013-06-01

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

  5. 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.

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

    PubMed

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

    2008-03-01

    The influence of ghrelin on feeding behaviour during infancy is unknown. To determine whether ghrelin influences milk intake in rat pups, newborn rats received a single i.p. injection of either rat ghrelin (100 microg/kg) or rabbit anti-ghrelin immunoglobulin G (100 microg/kg) every 5 days from postpartum day 5 to day 30 (P5-P30). Milk intake was then assessed by body weight gain following a 2-h suckling period. Ghrelin significantly increased weight gain relative to vehicle-injected controls in P20, P25 and P30 pups, but not in younger animals. Similarly, after 8 h of milk restriction, anti-ghrelin injections significantly decreased weight gain in P25 and P30, but not in younger pups. Interestingly, however, ghrelin did increase independent feeding in P10 and P15 pups using a paradigm in which pups consumed milk from a milk-soaked paper towel. We therefore conclude that ghrelin stimulates milk intake at an early postnatal stage, primarily by affecting adult-type feeding behaviour. PMID:18194428

  7. 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

  8. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

    PubMed Central

    KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

    2015-01-01

    The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

  9. The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats

    PubMed Central

    Dickerson, Sarah M.; Walker, Deena M.; Reveron, Maria E.; Duvauchelle, Christine L.; Gore, Andrea C.

    2009-01-01

    Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug ±-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal (HPG) reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA or saline either once (acute) or for 20 days (chronic), and were euthanized 7 days following last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone (LH) concentrations, and serum testosterone levels, as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the HPG axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. PMID:18309234

  10. 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

  11. Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult.

    PubMed

    Anseloni, V C Z; He, F; Novikova, S I; Turnbach Robbins, M; Lidow, I A; Ennis, M; Lidow, M S

    2005-01-01

    Recently, there has been a growing interest in long-term consequences of neonatal pain because modern neonatal intensive care units routinely employ procedures that cause considerable pain and may be followed by local inflammation and hyperalgesia lasting for several hours or even days. To address this question, we developed a rat model of short lasting (<2 days) early local inflammatory insult produced by a single injection of 0.25% carrageenan (CAR) into the plantar surface of a hindpaw. Previously, we demonstrated that rats receiving this treatment within the first week after birth grow into adults with a global reduction in responsiveness to acute pain. Here, we report that these animals also manifest a low anxiety trait associated with reduced emotional responsiveness to stress. This conclusion is based in the following observations: (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in the forced swim test, these rats exhibit behavioral characteristics associated with stronger ability for stress coping; and (c) these animals have reduced basal and stress-induced plasma levels of such stress-related neuroendocrine markers as corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In addition, we used DNA microarray and real-time reverse-transcriptase polymerase chain reaction to profile long-term changes in gene expression in the midbrain periaqueductal gray (PAG; a region involved in both stress and pain modulation) in our animal model. Among the affected genes, serotonergic receptors were particularly well represented. Specifically, we detected increase in the expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of these receptors are known to be involved in the anxiolytic and analgesic activity of the PAG. Finally, to determine whether neonatal inflammatory insult induces elevation in maternal care, which may play a role in generating long-term behavioral alterations seen in our model, we

  12. 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

  13. Behavioral effects of corpus callosum transection and environmental enrichment in adult rats.

    PubMed

    Miu, Andrei C; Heilman, Renata M; Paşca, Sergiu P; Stefan, Catrinel A; Spânu, Florina; Vasiu, Renata; Olteanu, Adrian I; Miclea, Mircea

    2006-09-15

    A common assumption about the corpus callosum transection (CCX) is that it only affects behaviors heavily relying on interhemispheric communication. However, cerebral laterality is ubiquitous across motor and perceptual, cognitive and emotional domains, and the corpus callosum is important for its establishment. Several recent studies showed that the partial denervation of the sensorimotor isocortex through CCX derepressed neural growth processes that were sensitive to motor demand (experience-dependent neural plasticity). We investigated whether the facilitatory effects of CCX on cortical neural plasticity, shaped by differential housing, extended beyond the motor domain. Adult rats were housed in enriched (EE), standard (SE) or impoverished environments (IE) for 10 weeks, that is, 2 weeks before they underwent CCX or sham surgery, and, then, 8 weeks throughout the experiments. After they recovered from surgery, the behavioral performance of rats was tested using open-field, spontaneous alternation in the T-maze, paw preference, Morris water maze, and tone fear conditioning. The results indicated that the effects of CCX and housing on open-field behavior were independent, with CCX increasing the time spent in the center of the field at the beginning of the observation (i.e., emotionality), and EE and IE increasing rearing (emotionality) and reducing teeth-chattering (habituation), respectively. CCX reduced the frequency of spontaneous alternation, denoting spatial working memory deficits, while housing did not influence this performance. Neither CCX, nor housing significantly affected paw preference lateralization, although CCX was associated with a leftward bias in paw preference. In the Morris water maze, housing had effects on spatial acquisition, while CCX reduced activity, without interfering with spatial memory. CCX did not influence tone fear conditioning, but context fear conditioning seemed to benefit from EE. We conclude that CCX in adult rats has subtle

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

    PubMed

    Fakoya, Francis Adelade; Caxton-Martins, Ezekiel Ademola

    2006-01-01

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

  15. Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat.

    PubMed

    Loy, David N; Talbott, Jason F; Onifer, Stephen M; Mills, Michael D; Burke, Darlene A; Dennison, Jessica B; Fajardo, Lili C; Magnuson, David S K; Whittemore, Scott R

    2002-10-01

    Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter. However, dorsal hemisections that interrupt dorsal columns/dorsal corticospinal tract (DC/CST) and DLF pathways do not produce persistent, severe locomotor deficits in the adult rat. We studied the contributions of myelinated tracts in the DLF and DC/CST to overground locomotion following complete conduction blockade of axons in the ventrolateral funiculus (VLF), a region important for locomotor movements and for transcranial magnetic motor-evoked potentials (tcMMEP). Animals received ethidium bromide plus photon irradiation to produce discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, combined VLF + DLF, or combined VLF + DC/CST. Open-field BBB scores and tcMMEPs were studied at 1, 2, 3, and 4 weeks postlesion. VLF lesions resulted in mean BBB scores of 17 at 4 weeks. VLF + DC/CST and VLF + DLF lesions resulted in mean BBB scores of 15.9 and 11.1, respectively. TcMMEPs were absent in all lesion types confirming VLF conduction blockade throughout the study. Our data indicate that significant contributions to locomotion from myelinated pathways within the rat DLF can be revealed when combined with simultaneous compromise of the VLF. PMID:12429203

  16. Alpha actin isoforms expression in human and rat adult cardiac conduction system.

    PubMed

    Orlandi, Augusto; Hao, Hiroyuki; Ferlosio, Amedeo; Clément, Sophie; Hirota, Seiichi; Spagnoli, Luigi Giusto; Gabbiani, Giulio; Chaponnier, Christine

    2009-04-01

    In the adult heart, cardiac muscle comprises the working myocardium and the conduction system (CS). The latter includes the sinoatrial node (SAN), the internodal tract or bundle (IB), the atrioventricular node (AVN), the atrioventricular bundle (AVB), the bundle branches (BB) and the peripheral Purkinje fibers (PF). Most of the information concerning the phenotypic features of CS tissue derives from the characterization of avian and rodent developing hearts; data concerning the expression of actin isoforms in adult CS cardiomyocytes are scarce. Using specific antibodies, we investigated the distribution of alpha-skeletal (alpha-SKA), alpha-cardiac (alpha-CA), alpha-smooth muscle (alpha-SMA) actin isoforms and other muscle-typical proteins in the CS of human and rat hearts at different ages. SAN and IB cardiomyocytes were characterized by the presence of alpha-SMA, alpha-CA, calponin and caldesmon, whereas alpha-SKA and vimentin were absent. Double immunofluorescence demonstrated the co-localisation of alpha-SMA and alpha-CA in I-bands of SAN cardiomyocytes. AVN, AVB, BB and PF cardiomyocytes were alpha-SMA, calponin, caldesmon and vimentin negative, and alpha-CA and alpha-SKA positive. No substantial differences in actin isoform distribution were observed in human and rat hearts, except for the presence of isolated subendocardial alpha-SMA positive cardiomyocytes co-expressing alpha-CA in the ventricular septum of the rat. Aging did not influence CS cardiomyocyte actin isoform expression profile. These findings support the concept that cardiomyocytes of SAN retain the phenotype of a developing myogenic cell throughout the entire life span. PMID:19281784

  17. 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

  18. 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

  19. Hormone responsiveness of cultured Sertoli cells obtained from adult rats after their rapid isolation under less harsh conditions.

    PubMed

    Gautam, M; Bhattacharya, I; Devi, Y S; Arya, S P; Majumdar, S S

    2016-05-01

    During adulthood, testicular Sertoli cells (Sc) coordinate all stages of germ cell (Gc) development involved in sperm production. However, our understanding about the functions of adult Sc is limited because of the difficulties involved in the process of isolating these cells from the adult testis, mainly because of the presence of large number of advanced Gc which interfere with Sc isolation at this age. Most of our knowledge about Sc function are derived from studies which used pre-pubertal rat Sc (18 ± 2-day old) as it is easy to isolate and culture Sc at this age. To this end, we established a less time consuming and less harsh procedure of isolating Sc from adult (60 days of age) rat testis for facilitating research on Sc-mediated regulation of spermatogenesis during adulthood. The cells were isolated using collagenase digestion at higher temperature, reducing the exposure time of cells to the enzyme. Step-wise digestion with intermittent removal of small clusters of tissue helped in increasing the yield of Sc. Isolated Sc were cultured and treated with FSH and testosterone (T) to evaluate their hormone responsiveness in terms of lactate, E2 , cAMP production. Adult Sc were found to be active and produced high amounts of lactate in a FSH-independent manner. FSH-mediated augmentation of cAMP and E2 production by adult Sc was less as compared with that by pre-pubertal Sc obtained from 18-day-old rats. Androgen-binding ability of adult Sc was significantly higher than pre-pubertal Sc. Although T treatment remarkably augmented expression of Claudin 11, it failed to augment lactate production by adult Sc. This efficient and rapid procedure for isolation and culture of functionally viable adult rat Sertoli cells may pave the way for determining their role in regulation and maintenance of spermatogenesis. PMID:26991307

  20. The Impact of Adult Vitamin D Deficiency on Behaviour and Brain Function in Male Sprague-Dawley Rats

    PubMed Central

    Turner, Karly M.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2013-01-01

    Background Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Methods Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. Results AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. Conclusions AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour. PMID:23951200

  1. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg;P=0.007), and nitric oxide synthase inhibition (withl-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment withl-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%;P<0.05), and this difference could be normalized byl-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. PMID:26928803

  2. Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats.

    PubMed

    Lazzaretti, Camilla; Kincheski, Grasielle Clotildes; Pandolfo, Pablo; Krolow, Rachel; Toniazzo, Ana Paula; Arcego, Danusa Mar; Couto-Pereira, Natividade de Sá; Zeidán-Chuliá, Fares; Galvalisi, Martin; Costa, Gustavo; Scorza, Cecilia; Souza, Tadeu Mello E; Dalmaz, Carla

    2016-03-01

    Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood. PMID:26620193

  3. Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

    PubMed

    Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

    2011-07-01

    Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. PMID:21185124

  4. Prenatal Stress Down-Regulates Reelin Expression by Methylation of Its Promoter and Induces Adult Behavioral Impairments in Rats

    PubMed Central

    Palacios-García, Ismael; Lara-Vásquez, Ariel; Montiel, Juan F.; Díaz-Véliz, Gabriela F.; Sepúlveda, Hugo; Utreras, Elías; Montecino, Martín; González-Billault, Christian; Aboitiz, Francisco

    2015-01-01

    Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new

  5. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    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 were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  6. 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 were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming". PMID:24275070

  7. 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…

  8. Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia.

    PubMed

    Tan, S; Zhi, P K; Luo, Z K; Shi, J

    2015-09-10

    Accumulated evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to stroke outcome. However, it is unclear whether hyperglycemia, which is frequently tested positive in patients with acute ischemic stroke, influences stroke-induced neurogenesis. The aim of the present study is to examine the effect of hyperglycemia on stroke-induced neurogenesis in a rat model of transient focal cerebral ischemia. For this purpose, adult male Sprague-Dawley rats (220-250 g) were subjected to 90 min of middle cerebral artery occlusion (MCAO). Glucose was administered during ischemia to produce target blood levels ranging from 4.83 ± 0.94 mM (normoglycemia) to 20.76 ± 1.56 mM. To label proliferating cells in ischemic ipsilateral subventricular zone (SVZ) of lateral ventricles, 5'-bromo-2'-deoxyuridine (BrdU) was injected 24h after MCAO. Brains were harvested 2h post-BrdU to evaluate the effects of hyperglycemia on infarct volume and SVZ cell proliferation. Rats that were severely hyperglycemic (19.26 ± 1.48 mM to 20.76 ± 1.56 mM) during ischemia had 24.26% increase in infarct volume (P<0.05) and more serious neurological function deficits (P<0.05). The severe hyperglycemic rats also showed dramatically decreased proliferation of neural stem/progenitor cells (NSPCs) (P<0.05) and down-regulation of the phosphorylation of cyclic-AMP response element-binding protein (pCREB) (P<0.05)and brain-derived neurotrophic factor (BDNF) (P<0.05) in ipsilateral SVZ. But the above-mentioned detrimental effects were not observed in rats that were rendered with mild hyperglycemia (9.43 ± 1.39-10.13 ± 1.24 mM). Our findings indicate that severe instead of mild hyperglycemia exacerbates ischemic injury and inhibits stroke-induced SVZ neurogenesis by a mechanism involving suppression of CREB and BDNF signaling. PMID:26126927

  9. Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

    PubMed

    Šlamberová, R; Pometlová, M; Schutová, B; Hrubá, L; Macúchová, E; Nová, E; Rokyta, R

    2012-01-01

    Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test. PMID:23130898

  10. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    SciTech Connect

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of (/sup 14/C)valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements.

  11. A search for residual behavioral effects of trichloroethylene (TCE) in rats exposed as young adults.

    PubMed

    Oshiro, Wendy M; Krantz, Q Todd; Bushnell, Philip J

    2004-01-01

    Trichloroethylene (TCE) is an organic solvent with robust acute effects on the nervous system, but poorly documented long-term effects. This study employed a signal detection task (SDT) to assess the persistence of effects of repeated daily inhalation of TCE on sustained attention in rats. Adult male Long-Evans rats inhaled TCE at 0, 1600, or 2400 ppm, 6 h/day for 20 days (n=8/group) and began learning the SDT 3 weeks later. Rats earned food by pressing one retractable response lever in a signal trial and a second lever in a blank (no signal) trial. TCE did not affect acquisition of the response rule or performance of the SDT after the intertrial interval (ITI) was changed from a constant value to a variable one. Increasing the trial presentation rate reduced accuracy equivalently in all groups. Injections of ethanol (0, 0.5, 1.0, 1.5 g/kg ip) and d-amphetamine (0, 0.1, 0.3, 1.0 mg/kg sc) systematically impaired performance as functions of drug dose. d-Amphetamine (1.0 mg/kg) reduced P(hit) more in the 2400-ppm TCE group than in the other groups. All rats required remedial training to learn a reversal of the response contingencies, which TCE did not interfere with. Thus, a history of exposure to TCE did not significantly alter learning or sustained attention in the absence of drugs. Although ethanol did not differentially affect the TCE groups, the effect of d-amphetamine is consistent with solvent-induced changes in dopaminergic functions in the CNS. Calculations indicated power values of 0.5 to 0.8 to detect main effects of TCE for the three primary endpoints. PMID:15019957

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

    PubMed

    Fakoya, Francis Adelade

    2005-06-01

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

  13. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    PubMed

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  14. Neonatal endotoxin exposure changes neuroendocrine, cardiovascular function and mortality during polymicrobial sepsis in adult rats.

    PubMed

    Saia, Rafael Simone; Oliveira-Pelegrin, Gabriela Ravanelli; da Silva, Maria Emília Nadaletto Bonifácio; Aguila, Fábio Alves; Antunes-Rodrigues, José; Rocha, Maria José Alves; Cárnio, Evelin Capellari

    2011-08-01

    Our aim was to investigate whether neonatal LPS challenge may improve hormonal, cardiovascular response and mortality, this being a beneficial adaptation when adult rats are submitted to polymicrobial sepsis by cecal ligation and puncture (CLP). Fourteen days after birth, pups received an intraperitoneal injection of lipopolysaccharide (LPS; 100μg/kg) or saline. After 8-12 weeks, they were submitted to CLP, decapitated 4, 6 or 24h after surgery and blood was collected for vasopressin (AVP), corticosterone and nitrate measurement, while AVP contents were measured in neurohypophysis, supra-optic (SON) and paraventricular (PVN) nuclei. Moreover, rats had their mean arterial pressure (MAP) and heart rate (HR) evaluated, and mortality and bacteremia were determined at 24h. Septic animals with neonatal LPS exposure had higher plasma AVP and corticosterone levels, and higher c-Fos expression in SON and PVN at 24h after surgery when compared to saline treated rats. The LPS pretreated group showed increased AVP content in SON and PVN at 6h, while we did not observe any change in neurohypophyseal AVP content. The nitrate levels were significantly reduced in plasma at 6 and 24h after surgery, and in both hypothalamic nuclei only at 6h. Septic animals with neonatal LPS exposure showed increase in MAP during the initial phase of sepsis, but HR was not different from the neonatal saline group. Furthermore, neonatally LPS exposed rats showed a significant decrease in mortality rate as well as in bacteremia. These data suggest that neonatal LPS challenge is able to promote beneficial effects on neuroendocrine and cardiovascular responses to polymicrobial sepsis in adulthood. PMID:21549159

  15. ONTOGENY OF ETHANOL INDUCED MOTOR IMPAIRMENT FOLLOWING ACUTE ETHANOL: ASSESSMENT VIA THE NEGATIVE GEOTAXIS REFLEX IN ADOLESCENT AND ADULT RATS

    PubMed Central

    Ramirez, Ruby Liane; Spear, Linda Patia

    2010-01-01

    Adolescent rats have been observed to be less sensitive than adults to a number of ethanol effects that may serve as feedback cues to reduce further ethanol intake. Among these findings are a few reports of attenuated sensitivities of adolescents to ethanol-induced motor impairment. The purpose of the present study was to further explore potential age-related differences in ethanol-induced motor impairment in both male and female adolescent (postnatal day [P]28–32), and adult (P68-72) Sprague-Dawley rats using an inclined plane assessment of the negative geotaxis reflex. Adult males displayed significant motor impairment at 1.5 g/kg, whereas adolescent males required higher doses, showing significant motor impairment only at doses of 2.25 g/kg ethanol or greater. Intoxicated practice did not significantly influence level of motor impairment at either age. When female rats of both ages were separately analyzed in terms of their response to ethanol, a dose of 1.5 g/kg ethanol was found to significantly impair adults, whereas adolescent females showed significant motor impairment when challenged with 2.25 g/kg but not 1.5 g/kg ethanol. Yet when the 1.5 g/kg data of females at the two ages were directly compared, no significant age difference was seen at this dose. These data document an attenuated sensitivity of adolescent relative to adult rats to the motor impairing effects of ethanol using a stationary inclined plane test, an effect particularly robust in male animals, and demonstrates the utility of this test for assessment of motor coordination in adolescent and adult rats. PMID:20138187

  16. Parenteral magnesium load testing with /sup 28/Mg in weanling and young adult rats

    SciTech Connect

    Caddell, J.L.; Calhoun, N.R.; Howard, M.P.; Patterson, K.Y.; Smith, J.C. Jr.

    1981-06-01

    A sound diagnostic test for Mg deficiency is needed. This is a report of the parenteral Mg load test conducted in weanling and young adult rats fed a purified basal diet containing 3 mg magnesium/100 g with 150 mg of added magnesium/100 g (control) or 0 added magnesium (deficient). Weanlings were studied at about 1 week of dietary treatment and young adults at 2 weeks. The protocol included: a) a 6-hour preload urinary collection; b) an intraperitoneal load of 15 mg of magnesium/kg (weanlings) or 12 mg/kg (young adults) with 2 microCi 28Mg given simultaneously with each load; c) a 6-hour postload urinary collection; d) chemical analysis of selected tissues and urine for Mg; and e) 28Mg counting 6 and 24 hours postload. Controls all excreted large amounts of Mg pre- and postload, retaining less than 26% of nonradioactive loads. They had high urinary 28Mg counts. In Mg-deficient animals, the concentration of Mg in bone more than halved. These animals avidly conserved Mg and retained over 85% of nonradioactive Mg loads. Their 28Mg activity in vital organs was 3--6 times greater than in controls. We concluded that the parenteral Mg load test reliably identifies severe Mg deficiency.

  17. Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

    PubMed

    Dorce, Ana Leticia Coronado; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2010-01-01

    The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner. PMID:19945531

  18. An ultrastructural study of the phagocytic activity of astrocytes in adult rat brain.

    PubMed Central

    al-Ali, S Y; al-Hussain, S M

    1996-01-01

    The role of adult astrocytes in the removal of cell debris and foreign particles following injury to the brain is controversial. This study was undertaken to elucidate the response of adult astrocytes to needle injury of the rat cerebral cortex, using a suspension of colloidal carbon as a marker for phagocytosis. Either a single or 2 successive injections of colloidal carbon suspension were made into the cerebral cortex. The animals were allowed to survive for periods of from 1 to 30 d. Unequivocal involvement of astrocytes in the removal of carbon particles was evident only in those brains which had been subjected to 2 successive injections of carbon. The particles were located in membrane-bound vacuoles and were subsequently sequestered in lysosomes. Carbon-containing astrocytes were observed in the immediate vicinity of the lesion, in the adjacent parenchyma, around blood vessels and abutting carbon-containing macrophages. This study demonstrates that adult astrocytes are involved in phagocytosis, but only as a second line of defence. The possible significance of carbon-laden astrocytes further away from the site of the lesion is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8621323

  19. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring. PMID:26224008

  20. Cocaine Sensitization Increases Kyphosis and Modulates Neural Activity in Adult Nulliparous Rats

    PubMed Central

    Nephew, Benjamin C.; Caffrey, Martha K.; Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

    Although data from both animals and humans suggests that adult cocaine use can have long term effects on behavior, it is unknown if prior cocaine use affects future maternal behavior in nulliparous females. In the current study, cocaine or saline was administered to adult female rats for 10 days, the animals were withdrawn from cocaine for 7 days, and the females were then exposed to donor pups to induce the expression of maternal behavior. Nulliparous females sensitized to cocaine were more likely to retrieve pups, spent more time caring for the pups, and were more likely to express full maternal behavior on day 8 of pup exposure. The fMRI data revealed significant effects of pup exposure in the hippocampal CA1 region, and effects of cocaine in the anterior thalamus and periaqueductal gray. Prior adult cocaine use may have lasting effects on offspring care, and this effect is not dependent on pup mediated effects or the endocrine changes of gestation and lactation. The present findings provide support for the hypothesis that maternal motivation to exhibit maternal behavior is enhanced by prior cocaine sensitization, possibly due to cross sensitization between cocaine and the natural reward of maternal behavior. PMID:24371520

  1. Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs

    PubMed Central

    Miyanohara, Atsushi; Kamizato, Kota; Juhas, Stefan; Juhasova, Jana; Navarro, Michael; Marsala, Silvia; Lukacova, Nada; Hruska-Plochan, Marian; Curtis, Erik; Gabel, Brandon; Ciacci, Joseph; Ahrens, Eric T; Kaspar, Brian K; Cleveland, Don; Marsala, Martin

    2016-01-01

    Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients. PMID:27462649

  2. Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.

    PubMed

    Miyanohara, Atsushi; Kamizato, Kota; Juhas, Stefan; Juhasova, Jana; Navarro, Michael; Marsala, Silvia; Lukacova, Nada; Hruska-Plochan, Marian; Curtis, Erik; Gabel, Brandon; Ciacci, Joseph; Ahrens, Eric T; Kaspar, Brian K; Cleveland, Don; Marsala, Martin

    2016-01-01

    Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients. PMID:27462649

  3. Maternal Exposure to Low Levels of Corticosterone during Lactation Protects against Experimental Inflammatory Colitis-Induced Damage in Adult Rat Offspring

    PubMed Central

    Petrella, Carla; Giuli, Chiara; Agostini, Simona; Bacquie, Valérie; Zinni, Manuela; Theodorou, Vassilia; Broccardo, Maria; Casolini, Paola; Improta, Giovanna

    2014-01-01

    Opposing emotional events (negative/trauma or positive/maternal care) during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a “positive” experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT) (0.2 mg/ml) during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid) was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake) and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R). All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also better adapted

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

    PubMed

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

    2016-05-01

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

  5. Extensor motoneurone properties are altered immediately before and during fictive locomotion in the adult decerebrate rat

    PubMed Central

    MacDonell, C W; Power, K E; Chopek, J W; Gardiner, K R; Gardiner, P F

    2015-01-01

    Key points This is the first report, in adult decerebrate rats, to examine intracellular hindlimb motoneurone properties during quiescence, fictive locomotion and a tonic period immediately before fictive locomotion that is characterized by increased peripheral nerve activity. It is shown for the first time during fictive locomotion that motoneurones become more responsive in the tonic period, suggesting that the motoneurone pool becomes primed before patterned motor output commences. Spike frequency adaptation exists in quiescence and during fictive locomotion during constant excitation with injected current but not during centrally driven fictive locomotion. Motoneurones within the extensor motor pool show changes in excitability even when they are not directly involved in locomotion. The data show increased responsiveness of motoneurones during locomotion via a lowered threshold for spike initiation and decreased rheobase. Abstract This study examined motoneurone properties during fictive locomotion in the adult rat for the first time. Fictive locomotion was induced via electrical stimulation of the mesencephalic locomotor region in decerebrate adult rats under neuromuscular blockade to compare basic and rhythmic motoneurone properties in antidromically identified extensor motoneurones during: (1) quiescence, before and after fictive locomotion; (2) the ‘tonic’ period immediately preceding locomotor-like activity, whereby the amplitude of peripheral flexor (peroneal) and extensor (tibial) nerves are increased but alternation has not yet occurred; and (3) locomotor-like episodes. Locomotion was identified by alternating flexor–extensor nerve activity, where the motoneurone either produced membrane oscillations consistent with a locomotor drive potential (LDP) or did not display membrane oscillation during alternating nerve activity. Cells producing LDPs were referred to as such, while those that did not were referred to as ‘idle’ motoneurones. LDP and

  6. PRENATAL COCAINE ELIMINATES THE SEX-DEPENDENT DIFFERENCES IN ACTIVATION OBSERVED IN ADULT RATS AFTER COCAINE CHALLENGE

    EPA Science Inventory

    In the adult rat, acute administration of cocaine results in enhanced expression of certain behaviors. his activation is often referred to as "stereotypy" because of its repetitive nature. epeated exposure to the same dose of cocaine does not result in tolerance or a diminution o...

  7. PULMONARY FUNCTION IN JUVENILE AND YOUNG ADULT RATS EXPOSED TO LOW-LEVEL NO2 WITH DIURNAL SPIKES

    EPA Science Inventory

    Pulmonary function was examined in juvenile and young adult Fischer-344 rats continuously exposed to NO2 (0.5, 1.0 or 2.0 ppm) for up to 6 weeks with twice daily 1 hr spikes equal to 3X the baseline concentration. The spike to baseline ratio was chosen to simulate morning and eve...

  8. EFFECTS OF SUBCHRONIC INHALATION OF LOW CONCENTRATIONS OF NITROGEN DIOXIDE. 1. THE PROXIMAL ALVEOLAR REGION OF JUVENILE AND ADULT RATS

    EPA Science Inventory

    Techniques were devised to isolate tissue from the epithelium of terminal airways and the alveoli proximal to the airways. One day old juveniles and six week old adult rats were exposed to either room air or 0.5 ppm NO2 for 23 hrs per day seven days per week. An additional group ...

  9. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  10. TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

    EPA Science Inventory

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

  11. ALKYLTIN INHIBITION OF ATPASE ACTIVITIES IN TISSUE HOMOGENATES AND SUBCELLULAR FRACTIONS FROM ADULT AND NEONATAL RATS (JOURNAL VERSION)

    EPA Science Inventory

    Inhibition of ATPase activities by triethyltin (TET), diethyltin (DET), monoethyltin (MET) and trimethyltin (TMT) was studied in homogenates of brain and liver from adult rats. MET did not produce significant inhibition. ATPase activities in brain and liver homogenates from TET-t...

  12. Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury.

    PubMed

    Bove, Geoffrey M; Harris, Michele Y; Zhao, Huaqing; Barbe, Mary F

    2016-02-15

    Key clinical features of carpal tunnel syndrome and other types of cumulative trauma disorders of the hand and wrist include pain and functional disabilities. Mechanistic details remain under investigation but may involve tissue inflammation and/or fibrosis. We examined the effectiveness of modeled manual therapy (MMT) as a treatment for sensorimotor behavior declines and increased fibrogenic processes occurring in forearm tissues of rats performing a high repetition high force (HRHF) reaching and grasping task for 12 weeks. Young adult, female rats were examined: food restricted control rats (FRC, n=12); rats that were trained for 6 weeks before performing the HRHF task for 12 weeks with no treatment (HRHF-CON, n=11); and HRHF task rats received modeled manual therapy (HRHF-MMT, n=5) for 5 days/week for the duration of the 12-week of task. Rats receiving the MMT expressed fewer discomfort-related behaviors, and performed progressively better in the HRHF task. Grip strength, while decreased after training, improved following MMT. Fibrotic nerve and connective tissue changes (increased collagen and TGF-β1 deposition) present in 12-week HRHF-CON rats were significantly decreased in 12-week HRHF-MMT rats. These observations support the investigation of manual therapy as a preventative for repetitive motion disorders. PMID:26810536

  13. Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats.

    PubMed

    Bourke, Chase H; Stowe, Zachary N; Neigh, Gretchen N; Olson, Darin E; Owens, Michael J

    2013-01-01

    Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10-20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication. PMID:23906943

  14. Effects of 6-hydroxydopamine lesioning of the medial prefrontal cortex on social interactions in adolescent and adult rats.

    PubMed

    Li, Chun-Rong; Huang, Guang-Biao; Sui, Zhi Yan; Han, Eui-Hyeog; Chung, Young-Chul

    2010-07-30

    Bilateral depletion of dopamine (DA) in the medial prefrontal cortex (mPFC) following local infusions of 6-hydroxydopamine (6-OHDA) was reported to affect mesolimbic DA neurotransmission and augment spontaneous and amphetamine-induced locomotion. However, the effects of 6-OHDA lesioning of the mPFC of adolescent rats have never been investigated. Given that dopaminergic neurons reach the peak of maturation during adolescence, we hypothesized that 6-OHDA lesioning of the mPFC during adolescence would have greater impact on subsequent behavioral parameters than would such lesioning during adulthood. The aim of this study was to investigate the effects of 6-OHDA lesioning of the mPFC on the open-field activities and novel investigative and socially interactive behaviors of adolescent and adult rats. Using a stereotaxic apparatus, 6-OHDA (8.0 microg) was injected bilaterally into the mPFC of adolescent and adult rats. After a 1-week recovery period, rats were placed in an open-field chamber, and spontaneous locomotion and other behaviors were monitored. Next, a novel toy was place in the center and behavioral responses were observed. One day later, socially interactive behaviors were measured by placing the lesioned rats into a cage with four unfamiliar rats matched for age. The tests of locomotor activity and novel investigative behaviors revealed no significant differences between the lesioned and sham groups of adolescent or adult rats. Grooming and socially interactive behaviors were significantly lower in the adolescent and adult lesioned groups than in each sham group. Interestingly, we observed more extensive impairment in socially interactive behaviors among the adolescent lesioned rats compared to the adult lesioned rats. The present study indicates that DA depletion in the mPFC causes significantly reduced grooming and socially interactive behaviors; this phenomenon may be comparable to the negative symptoms observed in schizophrenia. Further research is

  15. Abnormal secretion of reproductive hormones and antioxidant status involved in quinestrol-induced reproductive toxicity in adult male rat.

    PubMed

    Li, Jian; Wang, Hongwei; Zhang, Jiliang; Zhou, Bianhua; Si, Lifang; Wei, Lan; Li, Xiang

    2014-02-01

    This study aimed to evaluate the effects of quinestrol, a synthetic oestrogen homologue with reproductive toxicity, on the secretion of reproductive hormones and antioxidant status in adult male rat. Our results showed that quinestrol exposure significantly decreased the weight of the testis, epididymides, seminal vesicle, and prostate, as well as the sperm counts in the cauda epididymis of rats. Quinestrol significantly reduced the size of seminiferous tubules and the total number of spermatogenic cells. Serum testosterone, follitropin, and lutropin were also significantly reduced in a dose-related manner after quinestrol exposure. Meanwhile, the activity of superoxide dismutase, glutathione peroxidase, and total antioxide capacity significantly decreased, whereas the malondialdehyde and nitric oxide concentrations significantly increased in the testes. These findings revealed that endocrine disorders of reproductive hormones and oxidative stress may be involved in reproductive toxicity induced by quinestrol in adult male rats. PMID:24183492

  16. Perinatal undernutrition facilitates morphine sensitization and cross-sensitization to cocaine in adult rats: a behavioral and neurochemical study.

    PubMed

    Velazquez, E E; Valdomero, A; Orsingher, O A; Cuadra, G R

    2010-01-20

    The development of sensitization to the locomotor effects of morphine and cross-sensitization between morphine and cocaine were evaluated in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 30 days of age (D-rats), and compared with well-nourished animals (C-rats). Dose-response curves to morphine-induced locomotor activity (5, 7.5, 10 or 15 mg/kg, i.p., every other day for 5 days) revealed a shift to the left in D-rats compared to C-rats. This implies that D-rats showed behavioral sensitization to the lower dose of morphine used (5 mg/kg), which was ineffective in C-rats. Furthermore, when a cocaine challenge (10 mg/kg, i.p) was given 48 h after the last morphine administration, only D-rats exhibited cross-sensitization in morphine-pretreated animals (7.5 and 10 mg/kg). In order to correlate the differential response observed with the functioning of the mesocorticolimbic dopaminergic system, extracellular dopamine (DA) levels were measured in the nucleus accumbens (core and shell) and the dorsal caudate-putamen. A challenge with cocaine in morphine pre-exposed animals produced an increase in DA release, but only in the nucleus accumbens "core" of D-rats. Similar DA levels were found in the nucleus accumbens "shell" and in the dorsal caudate-putamen of both groups. Finally, these results demonstrate that D-rats had a lower threshold for developing both a progressive behavioral sensitization to morphine and a cross-sensitization to cocaine. In accordance with these behavioral findings, a higher responsiveness of the nucleus accumbens core, expressed by increased DA levels, both basal and after cocaine challenge, was observed in D-rats. PMID:19892003

  17. 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…

  18. A Coping Model for Adult Survivors of Childhood Sexual Abuse.

    ERIC Educational Resources Information Center

    Draucker, Claire B.

    1995-01-01

    A group of 149 adult survivors of childhood sexual abuse was tested using a causal model that identifies relationships among sexual abuse situation characteristics, the accomplishment of cognitive coping tasks, and long-term effects. Results indicated the model did not fit the data. A revised model is proposed and examined. (JBJ)

  19. Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

    PubMed

    Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

    2012-12-01

    Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats. PMID:22832793

  20. Intermittent prenatal MDMA exposure alters physiological but not mood related parameters in adult rat offspring.

    PubMed

    Adori, Csaba; Zelena, Dóra; Tímár, Júlia; Gyarmati, Zsuzsa; Domokos, Agnes; Sobor, Melinda; Fürst, Zsuzsanna; Makara, Gábor; Bagdy, György

    2010-01-20

    The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior. PMID:19782105

  1. Cardiopulmonary bypass model in the rat: a new minimal invasive model with a low flow volume†

    PubMed Central

    Lebreton, Guillaume; Tamion, Fabienne; Bessou, Jean-Paul; Doguet, Fabien

    2012-01-01

    Numerous cardiopulmonary bypass (CPB) models in the rat have already been described, but these models often have an important mortality and differ a lot from human clinical conditions thus making them hardly usable. The CPB model in the rat we describe allows a femoro-femoral support CPB with a low priming volume, minimal surgical approach and excellent peroperative survival. This CPB model in the rat allows evaluating extracorporeal circulation effects. PMID:22345055

  2. Animal models of neurological deficits: how relevant is the rat?

    PubMed

    Cenci, M Angela; Whishaw, Ian Q; Schallert, Timothy

    2002-07-01

    Animal models of neurological deficits are essential for the assessment of new therapeutic options. It has been suggested that rats are not as appropriate as primates for the symptomatic modelling of disease, but a large body of data argues against this view. Comparative analyses of movements in rats and primates show homology of many motor patterns across species. Advances have been made in identifying rat equivalents of akinesia, tremor, postural deficits and dyskinesia, which are relevant to Parkinson's disease. Rat models of hemiplegia, neglect and tactile extinction are useful in assessing the outcome of ischaemic or traumatic brain injury, and in monitoring the effects of therapeutic interventions. Studies in rodents that emphasize careful behavioural analysis should continue to be developed as effective and inexpensive models that complement studies in primates. PMID:12094213

  3. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one. PMID:25847268

  4. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

    SciTech Connect

    Krueger, Katharina Repges, Hendrik; Hippler, Joerg; Hartmann, Louise M.; Hirner, Alfred V.; Straub, Heidrun; Binding, Norbert; Musshoff, Ulrich

    2007-11-15

    In this study, the effects of pentavalent dimethylarsinic acid ((CH{sub 3}){sub 2}AsO(OH); DMA{sup V}) and trivalent dimethylarsinous acid ((CH{sub 3}){sub 2}As(OH); DMA{sup III}) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 {mu}mol/l. DMA{sup V} had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA{sup III} significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 {mu}mol/l DMA{sup III} in adult and 10 {mu}mol/l DMA{sup III} in young rats. Moreover, DMA{sup III} significantly affected the LTP-induction. Application of 10 {mu}mol/l DMA{sup III} resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA{sup III}. In slices of young rats, the depressant effects of DMA{sup III} were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA{sup V} on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential.

  5. A role for the prefrontal cortex in heroin-seeking after forced abstinence by adult male rats but not adolescents.

    PubMed

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-02-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. PMID:23072838

  6. A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

    PubMed Central

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-01-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir+ and Fos-ir− neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir+ neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. PMID:23072838

  7. Sex differences in anxiety-like behavior and locomotor activity following prenatal and postnatal methamphetamine exposure in adult rats.

    PubMed

    Hrubá, L; Schutová, B; Šlamberová, R

    2012-01-18

    The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behavior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure. PMID:21884713

  8. 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.

  9. Preweaning cocaine exposure alters brain glucose metabolic rates following repeated amphetamine administration in the adult rat.

    PubMed

    Melnick, Susan M; Torres-Reveron, Annelyn; Dow-Edwards, Diana L

    2004-10-15

    Developmental cocaine exposure produces long-term alterations in function of many neuronal circuits. This study examined glucose metabolic rates following repeated amphetamine administration in adult male and female rats pretreated with cocaine during postnatal days (PND) 11-20. PND11-20 cocaine increased the response to amphetamine in many components of the motor system and the dorsal caudate-putamen, in particular, and decreased the metabolic response in the hypothalamus. While amphetamine alone produced widespread increases in metabolism, there were no cocaine-related effects in the mesolimbic, limbic or sensory structures. These data suggest that a brief cocaine exposure during development can alter ontogeny and result in abnormal neuronal responses to repeated psychostimulant administration in adulthood. PMID:15464226

  10. Adolescent Intermittent Ethanol Exposure Is Associated with Increased Risky Choice and Decreased Dopaminergic and Cholinergic Neuron Markers in Adult Rats

    PubMed Central

    Boutros, Nathalie; Semenova, Svetlana; Liu, Wen; Crews, Fulton T.

    2015-01-01

    Background: Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats. Methods: Adolescent (postnatal day 28–53) rats were administered 5g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-days–on/2-days–off exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain. Results: All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice. Conclusions: The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences. PMID:25612895

  11. A Single Neonatal Injection of Ethinyl Estradiol Impairs Passive Avoidance Learning and Reduces Expression of Estrogen Receptor α in the Hippocampus and Cortex of Adult Female Rats

    PubMed Central

    Shiga, Tatsuomi; Nakamura, Takahiro J.; Komine, Chiaki; Goto, Yoshikuni; Mizoguchi, Yasushi; Yoshida, Midori; Kondo, Yasuhiko; Kawaguchi, Maiko

    2016-01-01

    Although perinatal exposure of female rats to estrogenic compounds produces irreversible changes in brain function, it is still unclear how the amount and timing of exposure to those substances affect learning function, or if exposure alters estrogen receptor α (ERα) expression in the hippocampus and cortex. In adult female rats, we investigated the effects of neonatal exposure to a model estrogenic compound, ethinyl estradiol (EE), on passive avoidance learning and ERα expression. Female Wistar-Imamichi rats were subcutaneously injected with oil, 0.02 mg/kg EE, 2 mg/kg EE, or 20 mg/kg 17β-estradiol within 24 h after birth. All females were tested for passive avoidance learning at the age of 6 weeks. Neonatal 0.02 mg/kg EE administration significantly disrupted passive avoidance compared with oil treatment in gonadally intact females. In a second experiment, another set of experimental females, treated as described above, was ovariectomized under pentobarbital anesthesia at 10 weeks of age. At 15–17 weeks of age, half of each group received a subcutaneous injection of 5 μg estradiol benzoate a day before the passive avoidance learning test. Passive avoidance learning behavior was impaired by the 0.02 mg/kg EE dose, but notably only in the estradiol benzoate-injected group. At 17–19 weeks of age, hippocampal and cortical samples were collected from rats with or without the 5 μg estradiol benzoate injection, and western blots used to determine ERα expression. A significant decrease in ERα expression was observed in the hippocampus of the estradiol-injected, neonatal EE-treated females. The results demonstrated that exposure to EE immediately after birth decreased learning ability in adult female rats, and that this may be at least partly mediated by the decreased expression of ERα in the hippocampus. PMID:26741502

  12. A Single Neonatal Injection of Ethinyl Estradiol Impairs Passive Avoidance Learning and Reduces Expression of Estrogen Receptor α in the Hippocampus and Cortex of Adult Female Rats.

    PubMed

    Shiga, Tatsuomi; Nakamura, Takahiro J; Komine, Chiaki; Goto, Yoshikuni; Mizoguchi, Yasushi; Yoshida, Midori; Kondo, Yasuhiko; Kawaguchi, Maiko

    2016-01-01

    Although perinatal exposure of female rats to estrogenic compounds produces irreversible changes in brain function, it is still unclear how the amount and timing of exposure to those substances affect learning function, or if exposure alters estrogen receptor α (ERα) expression in the hippocampus and cortex. In adult female rats, we investigated the effects of neonatal exposure to a model estrogenic compound, ethinyl estradiol (EE), on passive avoidance learning and ERα expression. Female Wistar-Imamichi rats were subcutaneously injected with oil, 0.02 mg/kg EE, 2 mg/kg EE, or 20 mg/kg 17β-estradiol within 24 h after birth. All females were tested for passive avoidance learning at the age of 6 weeks. Neonatal 0.02 mg/kg EE administration significantly disrupted passive avoidance compared with oil treatment in gonadally intact females. In a second experiment, another set of experimental females, treated as described above, was ovariectomized under pentobarbital anesthesia at 10 weeks of age. At 15-17 weeks of age, half of each group received a subcutaneous injection of 5 μg estradiol benzoate a day before the passive avoidance learning test. Passive avoidance learning behavior was impaired by the 0.02 mg/kg EE dose, but notably only in the estradiol benzoate-injected group. At 17-19 weeks of age, hippocampal and cortical samples were collected from rats with or without the 5 μg estradiol benzoate injection, and western blots used to determine ERα expression. A significant decrease in ERα expression was observed in the hippocampus of the estradiol-injected, neonatal EE-treated females. The results demonstrated that exposure to EE immediately after birth decreased learning ability in adult female rats, and that this may be at least partly mediated by the decreased expression of ERα in the hippocampus. PMID:26741502

  13. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats

    SciTech Connect

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-12-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 {mu}g/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor {beta} was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.

  14. Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats.

    PubMed

    Réus, Gislaine Z; Scaini, Giselli; Jeremias, Gabriela C; Furlanetto, Camila B; Morais, Meline O S; Mello-Santos, Lis Maira; Quevedo, João; Streck, Emilio L

    2014-10-01

    Methylphenidate (MPH) is commonly prescribed for children who have been diagnosed with attention deficit hyperactivity disorder (ADHD); however, the action mechanisms of methylphenidate have not been fully elucidated. Studies have shown a relationship between apoptosis signaling pathways and psychiatric disorders, as well as in therapeutic targets for such disorders. So, we investigated if chronic treatment with MPH at doses of 1, 2 and 10mg/kg could alter the levels of pro-apoptotic protein, Bax, anti-apoptotic protein, Bcl-2, caspase-3 and cytochrome c in the brain of young and adult Wistar rats. Our results showed that MPH at all doses increased Bax in the cortex; the Bcl-2 and caspase-3 were increased with MPH (1mg/kg) and were reduced with MPH (2 and 10mg/kg); the cytochrome c was reduced in the cortex after treatment with MPH at all doses; in the cerebellum there was an increase of Bax with MPH at all doses, however, there was a reduction of Bcl-2, caspase-3, and cytochrome c with MPH (2 and 10mg/kg); in the striatum the treatment with MPH (10mg/kg) decreased caspase-3 and cytochrome c; treatment with MPH (2 and 10mg/kg) increased Bax and decreased Bcl-2 in the hippocampus; and the caspase-3 and cytochrome c were reduced in the hippocampus with MPH (10mg/kg). In conclusion, our results suggest that MPH influences plasticity in the brain of young and adult rats; however, the effects were dependent of age and brain area, on the one hand activating the initial cascade of apoptosis, increasing Bax and reducing Bcl-2, but otherwise inhibiting apoptosis by reduction of caspase-3 and cytochrome c. PMID:25128604

  15. Sex Differences in Adult Cognitive Deficits after Adolescent Nicotine Exposure in Rats

    PubMed Central

    Pickens, Laura R. G.; Rowan, James D.; Bevins, Rick A.; Fountain, Stephen B.

    2013-01-01

    This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood. PMID:23673345

  16. Developmental Methoxychlor Exposure Affects Multiple Reproductive Parameters and Ovarian: Folliculogenesis and Gene Expression in Adult Rats

    PubMed Central

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-01-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 μg/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post-coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor β was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis. PMID:18848953

  17. Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

    PubMed

    Figueiredo, Mariana Sarto; da Conceição, Ellen Paula Santos; de Oliveira, Elaine; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar

    2015-10-14

    Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and adrenaline β2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11β-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11β-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during

  18. Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat.

    PubMed

    Cao, Qilin; Zhang, Yi Ping; Iannotti, Christopher; DeVries, William H; Xu, Xiao-Ming; Shields, Christopher B; Whittemore, Scott R

    2005-02-01

    A graded contusion spinal cord injury (SCI) was created in the adult rat spinal cord using the Infinite Horizons (IH) impactor to study the correlation between injury severity and anatomical, behavioral, and electrophysiological outcomes. Adult Fisher rats were equally divided into five groups and received contusion injuries at the ninth thoracic level (T9) with 100, 125, 150, 175, or 200 kdyn impact forces, respectively. Transcranial magnetic motor-evoked potentials (tcMMEPs) and BBB open-field locomotor analyses were performed weekly for 4 weeks postinjury. Our results demonstrated that hindlimb locomotor function decreased in accordance with an increase in injury severity. The locomotor deficits were proportional to the amount of damage to the ventral and lateral white matter (WM). Locomotor function was strongly correlated to the amount of spared WM, which contains the reticulospinal and propriospinal tracts. Normal tcMMEP latencies were recorded in control, all of 100-kdyn-injured and half of 125-kdyn-injured animals. Delayed latency responses were recorded in some of 125-kdyn-injured and all of 150-kdyn-injured animals. No tcMMEP responses were recorded in 175- and 200-kdyn-injured animals. Comparison of tcMMEP responses with areas of WM loss or demyelination identified the medial ventrolateral funiculus (VLF) as the location of the tcMMEP pathway. Immunohistochemical and electromicroscopic (EM) analyses showed the presence of demyelinated axons in WM tracts surrounding the lesion cavities at 28 days postinjury. These data support the notion that widespread WM damage in the ventral and lateral funiculi may be a major cause for locomotor deficits and lack of tcMMEP responses after SCI. PMID:15629760

  19. The turnover of myelin phospholipids in the adult and developing rat brain

    PubMed Central

    Jungalwala, F. B.; Dawson, R. M. C.

    1971-01-01

    1. Inorganic [32P]phosphate, [U-14C]glycerol and [2-14C]ethanolamine were injected into the lateral ventricles in the brains of adult rats, and the labelling of individual phospholipids was followed over 2–4 months in both a microsomal and a highly purified myelin fraction. 2. All the phospholipids in myelin became appreciably labelled, although initially the specific radioactivities of the microsomal phospholipids were somewhat higher. Eventually the specific radioactivities in microsomal and myelin phospholipids fell rapidly at a rate corresponding to the decline of radioactivity in the acid-soluble pools. 3. Equivalent experiments carried out in developing rats with [32P]phosphate administered at the start of myelination showed some persistence of phospholipid labelling in the myelin, but this could partly be attributed to the greater retention of 32P in the acid-soluble phosphorus pool and recycling. 4. It is concluded that a substantial part of the phospholipid molecules in adult myelin membranes is readily exchangeable, although a small pool of slowly exchangeable material also exists. 5. A slow incorporation into or loss of labelled precursor from myelin phospholipids does not necessarily give a good indication of the rate of renewal of the molecules in the membrane. As presumably such labelled molecules originate by exchange with those in another membrane site (not necessarily where synthesis occurs) it is only possible to calculate the turnover rate in the myelin membrane if the behaviour of the specific radioactivity with time of the phospholipid molecules in the immediate precursor pool is known. PMID:5124379

  20. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  1. Extensor motoneurone properties are altered immediately before and during fictive locomotion in the adult decerebrate rat.

    PubMed

    MacDonell, C W; Power, K E; Chopek, J W; Gardiner, K R; Gardiner, P F

    2015-05-15

    This study examined motoneurone properties during fictive locomotion in the adult rat for the first time. Fictive locomotion was induced via electrical stimulation of the mesencephalic locomotor region in decerebrate adult rats under neuromuscular blockade to compare basic and rhythmic motoneurone properties in antidromically identified extensor motoneurones during: (1) quiescence, before and after fictive locomotion; (2) the 'tonic' period immediately preceding locomotor-like activity, whereby the amplitude of peripheral flexor (peroneal) and extensor (tibial) nerves are increased but alternation has not yet occurred; and (3) locomotor-like episodes. Locomotion was identified by alternating flexor-extensor nerve activity, where the motoneurone either produced membrane oscillations consistent with a locomotor drive potential (LDP) or did not display membrane oscillation during alternating nerve activity. Cells producing LDPs were referred to as such, while those that did not were referred to as 'idle' motoneurones. LDP and idle motoneurones during locomotion had hyperpolarized spike threshold (Vth ; LDP: 3.8 mV; idle: 5.8 mV), decreased rheobase and an increased discharge rate (LDP: 64%; idle: 41%) during triangular ramp current injection even though the frequency-current slope was reduced by 70% and 55%, respectively. Modulation began in the tonic period immediately preceding locomotion, with a hyperpolarized Vth and reduced rheobase. Spike frequency adaptation did not occur in spiking LDPs or firing generated from sinusoidal current injection, but occurred during a sustained current pulse during locomotion. Input conductance showed no change. Results suggest motoneurone modulation occurs across the pool and is not restricted to motoneurones engaged in locomotion. PMID:25809835

  2. Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.

    PubMed Central

    Iñiguez, M A; Rodriguez-Peña, A; Ibarrola, N; Morreale de Escobar, G; Bernal, J

    1992-01-01

    The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain. Images PMID:1379612

  3. Hyparrhenia hirta: A potential protective agent against hematotoxicity and genotoxicity of sodium nitrate in adult rats.

    PubMed

    Bouaziz-Ketata, Hanen; Salah, Ghada Ben; Mahjoubi, Amira; Aidi, Zied; Kallel, Choumous; Kammoun, Hassen; Fakhfakh, Faiza; Zeghal, Najiba

    2015-11-01

    The present study was carried out to examine the adverse hematotoxic and genotoxic effects of water nitrate pollution on male adult rats and the use of hyparrhenia hirta methanolic extract in alleviating these effects. Sodium nitrate (NaNO3 ) was administered to adult rats by oral gavage at a dose of 400 mg kg(-1) bw daily for 50 days, while hyparrhenia hirta methanolic extract was given by drinking water at a dose of 1.5 mg mL(-1) (200 mg kg(-1) bw). The NaNO3 -treated group showed a significant decrease in red blood cell count, hemoglobin and hematocrit and a significant increase in total white blood cell, in neutrophil and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in treated groups compared to those of controls. Meanwhile, the results showed a marked reduction in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, along with an elevation in the level of lipid peroxidation and a reduction in the total glutathione content, indicating the induction of oxidative stress in the erythrocytes of NaNO3 -treated group. Interestingly, NaNO3 treatment showed a significant increase in the frequencies of total chromosomal aberrations, aberrant metaphases and micronucleus in bone-marrow cells. The oxidative stress induced by nitrate treatment might be the major cause for chromosomal rearrangements as free radicals leading to DNA damage. Hyparrhenia hirta methanolic extract appeared to be effective against hematotoxic and genotoxic changes induced by nitrate, as evidenced by the improvement of the markers cited above. PMID:24740966

  4. Inhibition of Adult Rat Retinal Ganglion Cells by D1-type Dopamine Receptor Activation

    PubMed Central

    Hayashida, Yuki; Rodríguez, Carolina Varela; Ogata, Genki; Partida, Gloria J.; Oi, Hanako; Stradleigh, Tyler W.; Lee, Sherwin C.; Colado, Anselmo Felipe; Ishida, Andrew T.

    2011-01-01

    The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D1a-receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D1-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats. These ligands curtailed repetitive spiking during constant current injections, and reduced the number and rate of rise of spikes elicited by fluctuating current injections without significantly altering the timing of the remaining spikes. Consistent with mediation by D1-type receptors, SCH-23390 reversed the effects of dopamine on spikes. Contrary to a recent report, spike inhibition by dopamine was not precluded by blocking Ih. Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na+ current (INa) amplitude and tetrodotoxin, at doses that reduced INa as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D1-type dopamine receptor activation can alter mammalian retinal ganglion cell excitability, and demonstrate that dopamine can modulate spikes in these cells by a mechanism different from the pre- and postsynaptic means proposed by previous studies. To our knowledge, our results also provide the first evidence that dopamine receptor activation can reduce excitability without altering the temporal precision of spike firing. PMID:19940196

  5. Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats.

    PubMed

    Ko, Meng-Chang; Hung, Yu-Hui; Ho, Pei-Yin; Yang, Yi-Ling; Lu, Kwok-Tung

    2014-12-01

    Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life. PMID:24945924

  6. Prenatal stress induces vulnerability to nicotine addiction and alters D2 receptors' expression in the nucleus accumbens in adult rats.

    PubMed

    Said, N; Lakehayli, S; El Khachibi, M; El Ouahli, M; Nadifi, S; Hakkou, F; Tazi, A

    2015-09-24

    Prenatal stress (PS) can induce several long-lasting behavioral and molecular abnormalities in rats. It can also be considered as a risk factor for many psychiatric diseases like schizophrenia, depression or PTSD and predispose to addiction. In this study, we investigated the effect of prenatal stress on the reinforcing properties of nicotine in the CPP paradigm. Then, we examined the mRNA expression of the D2 dopaminergic receptors using the quantitative real-time PCR technique in the nucleus accumbens (NAcc). We found that prenatally stressed rats exhibited a greater place preference for the nicotine-paired compartment than the control rats. Moreover, we observed an overexpression of the DRD2 gene in adult offspring stressed in utero and a downregulation in the PS NIC group (PS rats treated with nicotine) compared with their control counterparts (C NIC). These data suggest that maternal stress can permanently alter the offspring's addictive behavior and D2 receptors' expression. PMID:26192093

  7. Calcium antagonist flunarizine hydrochloride affects striatal D2 dopamine receptors in the young adult and aged rat brain.

    PubMed

    Asanuma, M; Ogawa, N; Haba, K; Hirata, H; Mori, A

    1991-01-01

    The calcium (Ca) antagonist flunarizine hydrochloride (FNZ) has been reported to induce parkinsonism, especially in the elderly. The effects of FNZ on dopamine receptors in rat striatal membranes, especially in aged rats, were studied using radiolabeled receptor assay. Similar displacing potencies in [(3)H]spiperone bindings were exhibited for FNZ and the Ca antagonists verapamil and nicardipine. FNZ was found to directly and competitively effect D2 receptors (D2-Rs) as an antagonist, without effecting D1 receptors. Furthermore, the washing of preoccupied membranes revealed that FNZ has a long-acting potent effect on D2-Rs. The comparative study of FNZ and sulpiride in young-adult and aged rats showed that the effect of FNZ on D2-Rs was more marked in aged rats. These results might be related to FNZ-induced parkinsonism and its high incidence in the elderly. PMID:15374420

  8. Fenugreek potent activity against nitrate-induced diabetes in young and adult male rats.

    PubMed

    El-Wakf, Azza M; Hassan, Hanaa A; Mahmoud, Ashraf Z; Habza, Marwa N

    2015-05-01

    Nitrate has described as an endocrine disruptor that promotes onset of diabetes. This study was undertaken to evaluate diabetic effect of high nitrate intake in young and adult male rats and its amelioration by fenugreek administration. The study revealed significant increase in serum glucose and blood glycosylated hemoglobin (HbA1c%), while serum insulin and liver glycogen were decreased among nitrate exposed animals, in particular the young group. A significant reduction in the body weight gain and serum thyroid hormones (T4 & T3) was also recorded. Further reduction in serum levels of urea and creatinine, as well as total protein in serum, liver and pancreas was demonstrated, with elevation in their levels in the urine of all nitrate exposed groups. Meanwhile, the activity of serum transaminases (ALT and AST) was increased, with decline in their activity in the liver tissue. In addition, an elevation in serum total bilirubin, tissues (liver and pancreas) nitric oxide and lipid profile, as well as liver activity of glucose-6-phosphatase was recorded. Fenugreek administration to nitrate exposed rats was found to be effective in alleviating hyperglycemia and other biochemical changes characterizing nitrate-induced diabetes. So, fenugreek can be considered to possess potent activity against onset of nitrate induced-diabetes. PMID:24615531

  9. Anterograde labeling of ventrolateral funiculus pathways with spinal enlargement connections in the adult rat spinal cord

    PubMed Central

    Reed, William R.; Shum-Siu, Alice; Whelan, Ashley; Onifer, Stephen M.; Magnuson, David S.K.

    2009-01-01

    The ventrolateral funiculus in the spinal cord has been identified as containing important ascending and descending pathways related to locomotion and interlimb coordination. The purpose of this descriptive study was to investigate the patterns of axon termination of long ascending and descending ventrolateral pathways within the cervical and lumbar enlargements of the adult rat spinal cord. To accomplish this, we made discrete unilateral injections of the tracer biotinylated dextran-amine (BDA) into the ventrolateral white matter at T9. Although some BDA-labeled axons with varicosities were found bilaterally at all cervical levels, particularly dense BDA-labeling was observed in laminae VIII and IX ipsilaterally at the C6 and C8 levels. In the same animals, dense terminal labeling was found in the lumbar enlargement in medial lamina VII and ventromedial laminae VIII and IX contralaterally. This labeling was most apparent in the more rostral lumbar segments. These observations continue the characterization of inter-enlargement (long propriospinal) pathways, illustrating a substantial and largely reciprocal inter-enlargement network with large numbers of both ascending and descending ventrolateral commissural neurons. These pathways are anatomically well-suited to the task of interlimb coordination and to participate in the remarkable recovery of locomotor function seen in the rat following thoracic spinal cord injuries that spare as little as 20% of the total white matter cross sectional area. PMID:19766612

  10. Metabolic alterations in liver and testes of adult and newborn rats following cadmium administration

    SciTech Connect

    Agarwal, A.K.

    1988-04-01

    A large number of studies have been conducted to understand the effect of cadmium on cellular intermediary metabolism. Although, most of the metal is stored in liver and kidney, the organ affected most in acute toxicity is testis. Increased lipid peroxidation and decreased mitochondrial respiration along with other cellular enzyme activities have been reported to take place due to cadmium administration. The present experiment was designed to study the effect of acute cadmium administration on the activities of some of the tissue enzyme systems that provide the reducing equivalent NADPH. The levels of NADH and NADPH were also measured. All the measurements were conducted in two tissues: liver and testes. The effect of simultaneous administration of zinc on cadmium induced changes was also determined. Newborn animals have been found to be resistant to many effects of cadmium. The present studies were also conducted in newborn rat liver and testes. The purpose of the study is to compare the effects of cadmium on adult and new born rats.

  11. Neurobehavioral assessment following e-cigarette refill liquid exposure in adult rats.

    PubMed

    Golli, Narges El; Dallagi, Yosra; Rahali, Dalila; Rejeb, Ines; Fazaa, Saloua El

    2016-07-01

    The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28 μl/kg of body weight of e-liquid with/without a dose of 0.5 mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short-term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela's inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out. PMID:27401341

  12. Lack of Reproductive Toxicity in Adult Male Rats Exposed to Interferon-Alpha.

    PubMed

    Rosa, Josiane de Lima; Cavariani, Marilia Martins; Borges, Cibele dos Santos; Leite, Gabriel Adan Araújo; Anselmo-Franci, Janete Aparecida; Kempinas, Wilma De Grava

    2015-01-01

    Interferon-alpha (IFN- α), a type I IFN, is a protein with antiviral, antiproliferative, and immunoregulatory activities, widely used in the treatment of several types of cancers as well as hepatitis B and C. Decrease of libido and erectile dysfunction are commonly reported by male patients during treatment of chronic hepatitis C with IFN- α . However, IFN therapy-associated underlying factors attributed to sexual dysfunction are still not well defined. Currently, there are few studies investigating the effects of IFN on male reproductive system functions. Given that, the aim of the present investigation was to examine effects of subchronic exposure to IFN- α (5 × 10(4) U/kg and 10 × 10(4) U/kg, 30 d) on serum hormones, sperm parameters, fertility, and testicular and epididymal hystopathology and morphometry in adult male Wistar rats. None of the evaluated parameters was markedly altered by IFN- α . Thus, our results suggest that exposure to IFN- α , in this experimental design, did not adversely affect sperm quality and fertile capacity of male rats. PMID:26488366

  13. Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats

    PubMed Central

    Li, Sheng-Guang; Wang, Jin-Yan; Luo, Fei

    2012-01-01

    Background Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent pain-related behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. Methodology/Principal Findings In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. Conclusions/Significance These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight the importance of treatment of chronic pain at an early stage. PMID:22574223

  14. Efficient estimation of the total number of acini in adult rat lung

    PubMed Central

    Barré, Sébastien F.; Haberthür, David; Stampanoni, Marco; Schittny, Johannes C.

    2014-01-01

    Abstract Pulmonary airways are subdivided into conducting and gas‐exchanging airways. An acinus is defined as the small tree of gas‐exchanging airways, which is fed by the most distal purely conducting airway. Until now a dissector of five consecutive sections or airway casts were used to count acini. We developed a faster method to estimate the number of acini in young adult rats. Right middle lung lobes were critical point dried or paraffin embedded after heavy metal staining and imaged by X‐ray micro‐CT or synchrotron radiation‐based X‐rays tomographic microscopy. The entrances of the acini were counted in three‐dimensional (3D) stacks of images by scrolling through them and using morphological criteria (airway wall thickness and appearance of alveoli). Segmentation stopper were placed at the acinar entrances for 3D visualizations of the conducting airways. We observed that acinar airways start at various generations and that one transitional bronchiole may serve more than one acinus. A mean of 5612 (±547) acini per lung and a mean airspace volume of 0.907 (±0.108) μL per acinus were estimated. In 60