Visuospatial asymmetries and interocular transfer in the split-brain rat.

PubMed

Adelstein, A; Crowne, D P

1991-06-01

Interocular transfer (IOT), hemispheric superiority, and cerebral dominance were examined in split-brain female albino rats. Callosum-sectioned and intact animals were monocularly trained in the Morris water maze and tested in IOT and reversal phases. In the IOT phase, split-brain rats entered more nontarget quadrants and headed less accurately toward the platform than did controls. For both split-brain animals and controls, right-eye training resulted in shorter latencies and fewer nontarget entries than did left-eye training. Analyses of cerebral dominance showed shorter latencies and smaller heading errors over all 3 phases in rats that were trained with the nondominant eye. Right-eye dominant controls were less affected by platform reversal. Split-brain rats were inferior to controls in latency to find the platform and in target quadrant entries. This finding establishes a spatial cognitive deficit from callosum section.

Effects of female sex hormones on expression of the Ang-(1-7)/Mas-R/nNOS pathways in rat brain.

PubMed

Cheng, Yuan; Li, Qiaoying; Zhang, Yidan; Wen, Quan; Zhao, Jianjun

2015-11-01

Female sex hormones are considered to reduce the risk of ischemic stroke. As a part of the renin-angiotensin system, angiotensin-(1-7) [Ang-(1-7)] has recently been reported to play a role in protecting neuronal tissues from ischemic stroke. Thus, we examined the effects of female sex hormones on the levels of Ang-(1-7) and its downstream pathways in the brain. Female rats were ovariectomized and 17β-estradiol (17β-EST), progesterone (PGR), or a combination of 17β-EST plus PGR were administered. Our data demonstrated that lack of female sex hormones significantly decreased the levels of Ang-(1-7) in the cerebral cortex and hippocampal CA1 area. Also, we observed a linear relationship between cortex levels of Ang-(1-7) and plasma brain natriuretic peptide levels (as an indicator for risk of ischemic stroke). We further showed that lack of female sex hormones decreased the expression of Ang-(1-7), Mas-receptor (Mas-R), and neuronal nitric oxide synthase (nNOS). Overall, our findings show for the first time that Ang-(1-7) and Mas-R/nNOS in the cortex are influenced by circulating 17β-EST and (or) PGR, whereas Ang-(1-7) and its pathways in the hippocampal CA1 area are primarily altered by 17β-EST. This suggests that female sex hormones play a role in regulating the expression of Ang-(1-7) and its pathways during ischemic brain injuries.

HIV-1 Proteins Accelerate HPA Axis Habituation in Female Rats

PubMed Central

Panagiotakopoulos, Leonidas; Kelly, Sean; Neigh, Gretchen N.

2015-01-01

Congenital infection by the Human Immunodeficiency Virus (HIV) has been shown to lead to multiple co-morbidities, and people living with HIV have a higher incidence of affective and anxiety disorders. A marked increase in mood disorders is evident during the sensitive phase of adolescence and this is further pronounced in females. Depression has been linked to dysfunction of the intracellular response system to corticosteroids at the level of the hippocampus (HC) and prefrontal cortex (PFC) with a notable role of the glucocorticoid receptor (GR) and its co-chaperones (FKBP5 and FKBP4). The current study examined the extent to which HIV protein expression in adolescent female rats altered the stress response at both the level of corticosterone output and molecular regulation of the glucocorticoid receptor in the brain. WT and HIV-1 genotype female rats were randomly allocated in control, acute stress and repeat stress groups. Corticosterone plasma levels and expression of GR, FKBP4, and FKBP5 in the HC and PFC were measured. The presence of HIV-1 proteins facilitate habituation of the corticosterone response to repeated stressors, such that HIV-1 TG rats habituated to repeated restraint and WT rats did not. This was reflected by interactions between stress exposure and HIV-1 protein expression at the level of GR co-chaperones. Although expression of the GR was similarly reduced after acute and repeat stress in both genotypes, expression of FKBP5 and FKBP4 was altered in a brain-region specific manner depending on the duration of the stress exposure and the presence or absence of HIV-1 proteins. Collectively, the data presented demonstrate that HIV-1 proteins accelerate habituation to repeated stressors and modify the influence of acute and repeat stressors on GR co-chaperones in a brain region-specific manner. PMID:25666308

Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

PubMed Central

Furuta, Miyako; Bridges, Robert S.

2009-01-01

The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

Repeated forced-swimming test in intact female rats: behaviour, oestrous cycle and enriched environment.

PubMed

Domingues, Karolina; Spezia, Inaê; Theindl, Lais C; Suman, Patrick R; Lima, Fernanda B; Lino de Oliveira, Cilene

2018-03-27

Psychopharmacology used animal models to study the effects of drugs on brain and behaviour. The repeated forced-swimming test (rFST), which is used to assess the gradual effects of antidepressants on rat behaviour, was standardized only in males. Because of the known sex differences in rats, experimental conditions standardized for males may not apply to female rats. Therefore, the present work aimed to standardize experimental and housing conditions for the rFST in female rats. Young or adult Wistar female rats were housed in standard or enriched environments for different experimental periods. As assessed in tested and nontested females, all rats had reached sexual maturity by the time behavioural testing occurred. The rFST consisted of a 15-min session of forced swimming (pretest), followed by 5-min sessions at 1 (test), 7 (retest 1) and 14 days (retest 2) later. The oestrous cycle was registered immediately before every behavioural session. All sessions were videotaped for further analysis. The immobility time of female rats remained similar over the different sessions of rFST independent of the age, the phase of the oestrous cycle or the housing conditions. These data indicate that rFST in female Wistar rats may be reproducible in different experimental conditions.

Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats

PubMed Central

2013-01-01

Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. PMID:24345032

Brain regional differences in social encounter-induced Fos expression in male and female rats after post-weaning social isolation.

PubMed

Ahern, Megan; Goodell, Dayton J; Adams, Jessica; Bland, Sondra T

2016-01-01

Early life adversity has been related to a number of psychological disorders including mood and other disorders that can manifest as inappropriate or aggressive responses to social challenges. The present study used post-weaning social isolation (PSI) in rats, a model of early life adversity, to examine its effects on Fos protein expression produced by exposure to a novel social encounter. We have previously reported that the social encounter-induced increase in Fos expression in the medial prefrontal cortex observed in group-housed controls (GRP) was attenuated in rats that had experienced PSI. Here we assessed Fos expression in other brain regions thought to be involved in emotion regulation and social behavior. Male and female rats were housed in same-sex groups or in isolation (ISO) for 4 weeks beginning on postnatal day (P) 21 and were exposed to a single 15 min social encounter with a novel same-sex conspecific on P49. Fos positive cells were assessed using immunohistochemistry in 16 regions within the forebrain. Exposure to a novel conspecific increased Fos expression in the forebrain of GRP rats in a region- and sex-specific fashion. This increase was blunted or absent in ISO rats within many regions including cortical regions, thalamus, habenula, dentate gyrus, lateral septum, and basolateral amygdala. In several regions, the increase in Fos was greater in male than in female group housed rats. Negative relationships were observed between social interactions and Fos in some regions. Forebrain hypofunction produced by early-life adversity may be involved in socially inappropriate behavior. Copyright © 2015 Elsevier B.V. All rights reserved.

Methamphetamine enhances sexual behavior in female rats.

PubMed

Winland, Carissa; Haycox, Charles; Bolton, Jessica L; Jampana, Sumith; Oakley, Benjamin J; Ford, Brittany; Ornelas, Laura; Burbey, Alexandra; Marquette, Amber; Frohardt, Russell J; Guarraci, Fay A

2011-06-01

The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual

Sexual differentiation of the adolescent rat brain: A longitudinal voxel-based morphometry study.

PubMed

Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta

2017-03-06

The sexual differentiation of the rat brain during the adolescent period has been well documented in post-mortem histological studies. However, to further understand the morphological changes occurring in the entire brain, a noninvasive neuroimaging method allowing an unbiased, comprehensive, and longitudinal investigation of brain morphology should be used. In this study, we investigated the sexual differentiation of the rat brain during the adolescent period using longitudinal voxel-based morphometry (VBM) analysis. Male and female Wistar rats (n=12 of each) were scanned in a 7.0-T MRI scanner at five time points from 6 to 10 weeks of age. The T2-weighted MRI images were segmented using the rat brain tissue priors that have been published by our laboratory. At the global level, the results of the VBM analysis showed greater increases in total gray matter volume in the males during the adolescent period, although we did not find significant differences in total white matter volume. At the voxel level, we found significant increases in the regional gray matter volume of the occipital cortex, amygdala, hippocampal formation, and cerebellum. At the regional level, only the occipital cortex in the females exhibited decreases during the adolescent period. These results were, at least in part, consistent with those of previous longitudinal VBM studies in humans, thus providing translational evidence of the sexual differentiation of the developing brain between rodents and humans. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation.

PubMed

Balietti, Marta; Giannubilo, Stefano R; Giorgetti, Belinda; Solazzi, Moreno; Turi, Angelo; Casoli, Tiziana; Ciavattini, Andrea; Fattorettia, Patrizia

2016-01-30

Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain. In females, interleukin 1 beta (IL1β) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1β and IL10 were significantly higher in treated rats. These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains. © 2015 Society of Chemical Industry.

Lifelong consumption of sodium selenite: gender differences on blood-brain barrier permeability in convulsive, hypoglycemic rats.

PubMed

Seker, F Burcu; Akgul, Sibel; Oztas, Baria

2008-07-01

The aim of this study was to compare the effects of hypoglycemia and induced convulsions on the blood-brain barrier permeability in rats with or without lifelong administration of sodium selenite. There is a significant decrease of the blood-brain barrier permeability in three brain regions of convulsive, hypoglycemic male rats treated with sodium selenite when compared to sex-matched untreated rats (p<0.05), but the decrease was not significant in female rats (p>0.05). The blood-brain barrier permeability of the left and right hemispheres of untreated, moderately hypoglycemic convulsive rats of both genders was better than their untreated counterparts (p<0.05). Our results suggest that moderate hypoglycemia and lifelong treatment with sodium selenite have a protective effect against blood-brain barrier permeability during convulsions and that the effects of sodium selenite are gender-dependent.

Social preference and maternal defeat-induced social avoidance in virgin female rats: sex differences in involvement of brain oxytocin and vasopressin.

PubMed

Lukas, Michael; Neumann, Inga D

2014-08-30

Research concerning non-reproductive sociability in rodents is mainly restricted to assessing the effects of oxytocin (OXT) and arginine-vasopressin (AVP) in male rats and mice. Comparable studies on natural social preference and social avoidance in females are substantially lacking. Here, we adapted a behavioral paradigm for monitoring social preference of female rats consisting of two consecutive exposures to either non-social or social stimuli. Further, to induce stimulus-specific social avoidance, female rats were exposed to a single 10-min maternal defeat by a lactating dam. Social preference towards same-sex conspecifics in female rats was shown to be independent of the estrous cycle and even more pronounced than in male rats. Intracerebroventricular (icv) application of OXT, AVP, or their selective receptor antagonists or agonists, did not alter naturally-occurring social preference in female rats. Stimulus-specific social avoidance could be induced by prior exposure to a lactating rat: an effect that could not be reversed/overcome by icv OXT. The female social preference paradigm for rats established in this study detected subtle sex differences in social preference behavior of rats. Further, stimulus-specific social deficits could be induced in female rats using an acute exposure to social defeat - as previously observed in male rodents. Female rats show strong social preference behavior, which can be prevented by social defeat, but does not seem to be regulated by the OXT or AVP systems. Accordingly, icv application of synthetic OXT does not reverse maternal defeat-induced social avoidance in female rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration.

PubMed

Ma, Zhiwei; Perez, Pablo; Ma, Zilu; Liu, Yikang; Hamilton, Christina; Liang, Zhifeng; Zhang, Nanyin

2018-04-15

Connectivity-based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting-state fMRI data and a novel, data-driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within-parcel homogeneity and high reproducibility across animals. Graph analysis of the whole-brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

PubMed Central

Bogdanova, Olena V.; Olson, Paul R.; Sung, Young-Hoon; D'Anci, Kristen E.; Renshaw, Perry F.

2015-01-01

Abstract Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52–60, 2015—Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males. PMID:25803141

Sex differences in the effects of adolescent stress on adult brain inflammatory markers in rats

PubMed Central

Pyter, Leah M.; Kelly, Sean D.; Harrell, Constance S.; Neigh, Gretchen N.

2013-01-01

Both basic and clinical research indicates that females are more susceptible to stress-related affective disorders than males. One of the mechanisms by which stress induces depression is via inflammatory signaling in the brain. Stress during adolescence, in particular, can also disrupt the activation and continued development of both the hypothalamic–pituitary–adrenal (HPA) and –gonadal (HPG) axes, both of which modulate inflammatory pathways and brain regions involved in affective behavior. Therefore, we tested the hypothesis that adolescent stress differentially alters brain inflammatory mechanisms associated with affective-like behavior into adulthood based on sex. Male and female Wistar rats underwent mixed-modality stress during adolescence (PND 37–48) and were challenged with lipopolysaccharide (LPS; 250 μg/kg, i.p.) or saline 4.5 weeks later (in adulthood). Hippocampal inflammatory marker gene expression and circulating HPA and HPG axes hormone concentrations were then determined. Despite previous studies indicating that adolescent stress induces affective-like behaviors in female rats only, this study demonstrated that adolescent stress increased hippocampal inflammatory responses to LPS in males only, suggesting that differences in neuroinflammatory signaling do not drive the divergent affective-like behaviors. The sex differences in inflammatory markers were not associated with differences in corticosterone. In females that experienced adolescent stress, LPS increased circulating estradiol. Estradiol positively correlated with hippocampal microglial gene expression in control female rats, whereas adolescent stress negated this relationship. Thus, estradiol in females may potentially protect against stress-induced increases in neuroinflammation. PMID:23348027

The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.

PubMed

Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C; Morgan, Todd E; Finch, Caleb E; Pike, Christian J; Mack, Wendy J; Cadenas, Enrique; Brinton, Roberta D

2015-07-01

The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1α) signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypometabolic conditions such as Alzheimer's. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulation of sexual odor preference by sex steroids in the posterodorsal medial amygdala in female rats.

PubMed

Fujiwara, Masaya; Nitta, Asano; Chiba, Atsuhiko

2016-06-01

Our previous study in male rats demonstrated that bilateral administration of flutamide, an androgen receptor (AR) antagonist, into the posterodorsal medial amygdala (MePD) increased the time sniffing male odors to as high as that sniffing estrous odors, eliminating the preference for estrous odors over male odors. This made us speculate that under blockade of AR in the MePD, testosterone-derived estrogen acting on the same brain region arouses interest in male odors which is otherwise suppressed by concomitant action of androgen. In cyclic female rats, endogenous androgen has been thought to be involved in inhibitory regulation of estrogen-activated sexual behavior. Thus, in the present study, we investigated the possibility that in female rats the arousal of interest in male odors is also normally regulated by both estrogen and androgen acting on the MePD, as predicted by our previous study in male rats. Implantation of either the estrogen receptor blocker tamoxifen (TX) or a non-aromatizable androgen 5α-dihydrotestosterone (DHT) into the MePD of ovariectomized, estrogen-primed female rats eliminated preference for male odors over estrous odors by significantly decreasing the time sniffing male odors to as low as that sniffing estrous odors. The subsequent odor discrimination tests confirmed that the DHT and TX administration did not impair the ability to discriminate between male and estrous odors. These results suggest that in estrous female rats estrogen action in the MePD plays critical roles in the expression of the preference for male odors while androgen action in the same brain region interferes with the estrogen action. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

PubMed

Tujioka, Kazuyo; Thanapreedawat, Panicha; Yamada, Takashi; Yokogoshi, Hidehiko; Horie, Kenji; Kim, Mujo; Tsutsui, Kazumi; Hayase, Kazutoshi

2014-01-01

The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, p<0.01). These results suggest that the administration of GABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

Nuclear receptor coactivators function in estrogen receptor- and progestin receptor-dependent aspects of sexual behavior in female rats

PubMed Central

Molenda-Figueira, Heather A.; Williams, Casey A.; Griffin, Andreana L.; Rutledge, Eric M.; Blaustein, Jeffrey D.; Tetel, Marc J.

2008-01-01

The ovarian hormones, estradiol (E) and progesterone (P) facilitate the expression of sexual behavior in female rats. E and P mediate many of these behavioral effects by binding to their respective intracellular receptors in specific brain regions. Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro. Previously, our lab has shown that SRC-1 and CBP modulate estrogen receptor (ER)-mediated induction of progestin receptor (PR) gene expression in the ventromedial nucleus of the hypothalamus (VMN) and hormone-dependent sexual receptivity in female rats. Female sexual behaviors can be activated by high doses of E alone in ovariectomized rats, and thus are believed to be ER-dependent. However, the full repertoire of female sexual behavior, in particular, proceptive behaviors such as hopping, darting and ear wiggling, are considered to be PR-dependent. In the present experiments, the function of SRC-1 and CBP in distinct ER- (Exp. 1) and PR- (Exp. 2) dependent aspects of female sexual behavior was investigated. In Exp. 1, infusion of antisense oligodeoxynucleotides to SRC-1 and CBP mRNA into the VMN decreased lordosis intensity in rats treated with E alone, suggesting that these coactivators modulate ER-mediated female sexual behavior. In Exp. 2, antisense to SRC-1 and CBP mRNA around the time of P administration reduced PR-dependent ear wiggling and hopping and darting. Taken together, these data suggest that SRC-1 and CBP modulate ER and PR action in brain and influence distinct aspects of hormone-dependent sexual behaviors. These findings support our previous studies and provide further evidence that SRC-1 and CBP function together to regulate ovarian hormone action in behaviorally-relevant brain regions. PMID:16769066

Effect of treatment at weaning with the serotonin antagonist mianserin on the brain serotonin and cerebrospinal fluid nocistatin level of adult female rats: a case of late imprinting.

PubMed

Csaba, G; Knippel, Barbara; Karabélyos, Cs; Inczefi-Gonda, Agnes; Hantos, Mónika; Tóthfalusi, L; Tekes, Kornélia

2004-07-09

Four weeks old (weanling) female rats were treated with the tricyclic antidepressant and histamine/serotonin receptor blocker mianserin for studying its faulty hormonal imprinting effect. Measurements were done four months later. Brain serotonin levels significantly decreased in four regions (hippocampus, hypothalamus, striatum and brainstem), without any change in the cortex. Sexual activity of the treated and control rats was similar. Cerebrospinal fluid nocistatin level was one magnitude higher in the treated rats, than in the controls. The density of uterine estrogen receptors was significantly reduced, while binding capacity of glucocorticoid receptors of liver and thymus remained at control level. The results call attention to the possibility of 1. a broad spectrum imprinting at the time of weaning by a receptor level acting non-hormone molecule 2. imprinting of the brain in a non-neonatal period of life and 3. a very durable (lifelong?) effect of the late imprinting with an antidepressant.

Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain

PubMed Central

Spivey, Jaclyn M.; Padilla, Eimeira; Shumake, Jason D.; Gonzalez-Lima, F.

2010-01-01

This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life. PMID:20969837

Reversal of prenatal morphine exposure-induced memory deficit in male but not female rats.

PubMed

Nasiraei-Moghadam, Shiva; Sherafat, Mohammad Amin; Safari, Mir-Shahram; Moradi, Fatemeh; Ahmadiani, Abolhassan; Dargahi, Leila

2013-05-01

Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M₁₋₁₃, or to the time of delivery, M₁₋₂₁. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M₁₋₁₃ and M₁₋₂₁ groups. Adolescent and adult male offspring were similar to control animals in M₁₋₁₃ group. However M₁₋₂₁ impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M₁₋₁₃ and M₁₋₂₁ adolescent and adult female rats, but only in M₁₋₂₁ adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.

Activation patterns of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile male and female rats.

PubMed

Reppucci, C J; Gergely, C K; Veenema, A H

2018-02-09

Social play is a highly rewarding and motivated behavior predominately displayed by juveniles and expressed by nearly all mammalian species. Prior work suggested that the vasopressin (AVP) and oxytocin (OT) systems can regulate the expression of social play in sex-specific ways. Here we investigated whether there are sex differences in the recruitment of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile rats. Single-housed rats were allowed to play, in their home cage, with an age- and sex-matched unfamiliar conspecific for 10 min, or received similar handling but no partner. Double-labeled fluorescent immunohistochemistry for Fos and either AVP or OT was completed in adjacent series of tissue to determine recruitment of AVP- and OT-immunoreactive neurons in response to social play. Exposure to social play did not increase recruitment of AVP or OT neurons in the supraoptic (SO) or paraventricular (PVH) hypothalamic nuclei of either sex compared to the no-play control condition. Interestingly, there was a robust sex difference in SO recruitment, irrespective of social play condition, with males exhibiting twice the recruitment of SO-AVP and SO-OT neurons compared to females. Lastly, exposure to social play increased recruitment of the posterior bed nuclei of the stria terminalis (pBST) and the posterodorsal medial amygdalar nucleus (MEApd) compared to the no-play control condition, and this effect was most pronounced in females. Our findings revealed sex differences in the recruitment of brain regions (i) independent of play condition (i.e., SO) possibly representing a sex difference in the baseline levels of AVP and OT signaling required for typical functioning and (ii) specific to play condition (i.e., pBST, MEApd). In sum, this study provides further evidence that the neural substrates underlying social play behavior are sex-specific. This article is protected by copyright. All rights reserved. This article is protected

Brain oxytocin: a key regulator of emotional and social behaviours in both females and males.

PubMed

Neumann, I D

2008-06-01

In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.

Social transmission of Pavlovian fear: fear-conditioning by-proxy in related female rats.

PubMed

Jones, Carolyn E; Riha, Penny D; Gore, Andrea C; Monfils, Marie-H

2014-05-01

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing). Individuals can also acquire fear from a social context, such as through observing the fear expression of a conspecific. In the current study, we examined the influence of kinship/familiarity on social transmission of fear in female rats. Rats were housed in triads with either sisters or non-related females. One rat from each cage was fear conditioned to a tone CS+ shock US. On day two, the conditioned rat was returned to the chamber accompanied by one of her cage mates. Both rats were allowed to behave freely, while the tone was played in the absence of the foot-shock. The previously untrained rat is referred to as the fear-conditioned by-proxy (FCbP) animal, as she would freeze based on observations of her cage-mate's response rather than due to direct personal experience with the foot-shock. The third rat served as a cage-mate control. The third day, long-term memory tests to the CS were performed. Consistent with our previous application of this paradigm in male rats (Bruchey et al. in Behav Brain Res 214(1):80-84, 2010), our results revealed that social interactions between the fear conditioned and FCbP rats on day two contribute to freezing displayed by the FCbP rats on day three. In this experiment, prosocial behavior occurring at the termination of the cue on day two was significantly greater between sisters than their non-sister counterparts, and this behavior resulted in increased freezing on day three. Our results suggest that familiarity and/or kinship influences the social transmission of fear in female rats.

Genotoxicity of Styrene–Acrylonitrile Trimer in Brain, Liver, and Blood Cells of Weanling F344 Rats

PubMed Central

Hobbs, Cheryl A.; Chhabra, Rajendra S.; Recio, Leslie; Streicker, Michael; Witt, Kristine L.

2012-01-01

Styrene–acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer. PMID:22351108

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats.

PubMed

Tenorio, Neuli M; Ribeiro, Daniel A; Alvarenga, Tathiana A; Fracalossi, Ana Carolina C; Carlin, Viviane; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica L

2013-01-01

The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Cannabinoid receptor expression and phosphorylation are differentially regulated between male and female cerebellum and brain stem after repeated stress: implication for PTSD and drug abuse.

PubMed

Xing, Guoqiang; Carlton, Janis; Zhang, Lei; Jiang, Xiaolong; Fullerton, Carol; Li, He; Ursano, Robert

2011-09-08

Recent study demonstrated a close relationship between cerebellum atrophy and symptom severity of pediatric maltreatment-related posttraumatic stress disorder (PTSD). It has also been known that females are more vulnerable than males in developing anxiety disorders after exposure to traumatic stress. The mechanisms are unknown. Because cannabinoid receptors (CB₁ and CB₂) are neuroprotective and highly expressed in the cerebellum, we investigated cerebellar CB expression in stressed rats. Young male and female Sprague-Dawley rats were given 40 unpredictable electric tail-shocks for 2h daily on 3 consecutive days. CB₁ and CB₂ mRNA and protein levels in rat cerebellum and brain stem were determined using quantitative real-time PCR and Western blot, respectively. Two-way ANOVA revealed significant gender and stress effects on cerebellar CB₁ mRNA expression, with females and non-stressed rats exhibiting higher CB₁ mRNA levels than the males (3 fold, p<0.01) and stressed rats (30%, p<0.01), respectively. CB₁ and CB₂ mRNA levels in brain stem were also greater in female rats than males (p<0.01, p<0.05, respectively). Repeated stress increased the level of phosphorylated CB₁ receptors, the inactivated CB₁, in rat cerebellum (p<0.01), particularly in female rats as revealed by the significant gender × stress interaction. Thus, repeated severe stress caused greater CB₁ mRNA suppression and CB₁ receptor phosphorylation in female cerebellum that could lead to increased susceptibility to stress-related anxiety disorders including PTSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Blood Brain Barrier and Neuroinflammation Are Critical Targets of IGF-1-Mediated Neuroprotection in Stroke for Middle-Aged Female Rats

PubMed Central

Bake, Shameena; Selvamani, Amutha; Cherry, Jessica; Sohrabji, Farida

2014-01-01

Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF)-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1’s neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h) indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1. KEGG pathway analysis implicated these miRNA in PI3K-Akt signaling, cell adhesion/ECM receptor pathways and T-and B-cell signaling. Specific components of these pathways were subsequently analyzed in vehicle and IGF-1 treated middle-aged females. Phospho-Akt was reduced by ischemia at 4h, but elevated by IGF-1 treatment at 24h. IGF-1 induced Akt activation was preceded by a reduction of blood brain barrier permeability at 4h post-stroke and global suppression of cytokines including IL-6, IL-10 and TNF-α. A subset of these cytokines including IL-6 was also suppressed by IGF-1 at 24h post-stroke. These data are the first to show that the temporal and mechanistic components of post-stroke IGF-1 treatment in older animals, and that cellular components of the blood brain barrier may serve as critical targets of IGF-1 in the aging brain. PMID:24618563

Long-term effects of in utero and lactational exposure to butyl paraben in female rats.

PubMed

Guerra, Marina Trevizan; Sanabria, Marciana; Cagliarani, Stephannie Vieira; Leite, Gabriel Adan Araújo; Borges, Cibele Dos Santos; De Grava Kempinas, Wilma

2017-03-01

Parabens are used as preservatives in cosmetic, pharmaceutical, and food industries, and are frequently detected as contaminants in human fluids and tissues. The endocrine disrupting effects of parabens in female rodents include uterotrophic response, steroidogenesis impairment, and ovarian disturbances. The objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on female sexual development. Pregnant Wistar rats were treated subcutaneously with either corn oil or BP at doses of 10, 100, or 200 mg/kg, from gestational day (GD) 12 until GD 20 for female foetal gonad evaluation, and from GD 12 until the end of lactation to evaluate sexual parameters on the female offspring. Immature female rats were also used in the uterotrophic assay to evaluate the possible estrogenic action of parabens. Our results revealed that, in this experimental protocol, BP did not show estrogenic activity at the doses used and did not impair sexual development and fertility capacity in the female rats, but impaired sexual behavior. We conclude that brain sexual development may be more sensitive to BP effects and we speculate that doses higher than 100 mg/kg (the male lowest observed adverse effect level (LOAEL) for rodent reproductive parameters) would be necessary to promote damages in the female reproduction, regarding the same protocol of exposure. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 776-788, 2017. © 2016 Wiley Periodicals, Inc.

Aging, estradiol and time of day differentially affect serotonin transporter binding in the central nervous system of female rats.

PubMed

Krajnak, Kristine; Rosewell, Katherine L; Duncan, Marilyn J; Wise, Phyllis M

2003-11-14

Estrogen-related changes in serotonergic neuronal transmission, including changes in the number of serotonin transporter (SERT) binding sites, have been cited as a possible cause for changes in mood, memory and sleep that occur during the menopausal transition. However, both aging and estradiol regulate SERT binding sites in the brain. The goal of this experiment was to determine how aging and estrogen interact to regulate SERT levels in the forebrain of young and reproductively senescent female Sprague-Dawley rats using [3H]paroxetine. The density of specific [3H]paroxetine binding in various brain regions was compared in young (2-4 months) and reproductively senescent (10-12 months) female rats at three times of day. In most brain regions examined, estrogen and aging independently increased the number of [3H]paroxetine binding sites. The only region that displayed a reduction in [3H]paroxetine binding with age was the suprachiasmatic nucleus (SCN). Time of day influenced [3H]paroxetine binding in the SCN and the paraventricular thalamus (PVT), two regions known to be involved in the regulation of circadian rhythms. Aging and/or estrogen also altered the pattern of binding in these regions. Thus, based on the results of this study, we conclude that aging and estrogen both act to regulate SERT binding sites in the forebrain of female rats, and that this regulation is region specific.

Binge ethanol effects on prefrontal cortex neurons, spatial working memory and task-induced neuronal activation in male and female rats.

PubMed

West, Rebecca K; Maynard, Mark E; Leasure, J Leigh

2018-05-01

Excessive alcohol intake is associated with a multitude of health risks, especially for women. Recent studies in animal models indicate that the female brain is more negatively affected by alcohol, compared to the male brain. Among other regions, excessive alcohol consumption damages the frontal cortex, an area important for many functions and decision making of daily life. The objective of the present study was to determine whether the medial prefrontal cortex (mPFC) in female rats is selectively vulnerable to alcohol-induced damage. In humans, loss of prefrontal grey matter resulting from heavy alcohol consumption has been documented, however this volume loss is not necessarily due to a decrease in the number of neurons. We therefore quantified both number and nuclear volume of mPFC neurons following binge alcohol, as well as performance and neuronal activation during a prefrontal-dependent behavioral task. Adult male and female Long-Evans rats were assigned to binge or control groups and exposed to ethanol using a well-established 4-day model of alcohol-induced neurodegeneration. Both males and females had significantly smaller average neuronal nuclei volumes than their respective control groups immediately following alcohol binge, but neither sex showed a decrease in neuron number. Binged rats of both sexes initially showed spatial working memory deficits. Although they eventually achieved control performance, binged rats of both sexes showed increased c-Fos labeling in the mPFC during rewarded alternation, suggesting decreased neural efficiency. Overall, our results substantiate prior evidence indicating that the frontal cortex is vulnerable to alcohol, but also indicate that sex-specific vulnerability to alcohol may be brain region-dependent. Copyright © 2018 Elsevier Inc. All rights reserved.

"Sexy stimulants": the interaction between psychomotor stimulants and sexual behavior in the female brain.

PubMed

Guarraci, Fay A; Bolton, Jessica L

2014-06-01

Research indicates gender differences in sensitivity to psychomotor stimulants. Preclinical work investigating the interaction between drugs of abuse and sex-specific behaviors, such as sexual behavior, is critical to our understanding of such gender differences in humans. A number of behavioral paradigms can be used to model aspects of human sexual behavior in animal subjects. Although traditional assessment of the reflexive, lordosis posture of the female rat has been used to map the neuroanatomical and neurochemical systems that contribute to uniquely female copulatory behavior, the additional behavioral paradigms discussed in the current review have helped us expand our description of the appetitive and consummatory patterns of sexual behavior in the female rat. Measuring appetitive behavior is particularly important for assessing sexual motivation, the equivalent of "desire" in humans. By investigating the effects of commonly abused drugs on female sexual motivation, we are beginning to elucidate the role of dopaminergic neurotransmission, a neural system also known to be critical to the neurobiology of drug addiction, in female sexual motivation. A better understanding of the nexus of sex and drugs in the female brain will help advance our understanding of motivation in general and explain how psychomotor stimulants affect males and females differently. Copyright © 2013 Elsevier Inc. All rights reserved.

Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

PubMed

Pic-Taylor, Aline; da Motta, Luciana Gueiros; de Morais, Juliana Alves; Junior, Willian Melo; Santos, Alana de Fátima Andrade; Campos, Leandro Ambrósio; Mortari, Marcia Renata; von Zuben, Marcus Vinicius; Caldas, Eloisa Dutra

2015-09-01

Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats.

PubMed

Dai, S-Y; Fan, J; Shen, Y; He, J-J; Peng, W

2016-05-01

Endoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension. Male, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin. ANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females. The results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

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

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

PubMed Central

da Silva, Fernando B. R.; Cunha, Polyane A.; Ribera, Paula C.; Barros, Mayara A.; Cartágenes, Sabrina C.; Fernandes, Luanna M. P.; Teixeira, Francisco B.; Fontes-Júnior, Enéas A.; Prediger, Rui D.; Lima, Rafael R.; Maia, Cristiane S. F.

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats.

PubMed

da Silva, Fernando B R; Cunha, Polyane A; Ribera, Paula C; Barros, Mayara A; Cartágenes, Sabrina C; Fernandes, Luanna M P; Teixeira, Francisco B; Fontes-Júnior, Enéas A; Prediger, Rui D; Lima, Rafael R; Maia, Cristiane S F

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Development of rat female genital cortex and control of female puberty by sexual touch

PubMed Central

Lenschow, Constanze; Sigl-Glöckner, Johanna

2017-01-01

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch. PMID:28934203

Development of rat female genital cortex and control of female puberty by sexual touch.

PubMed

Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

2017-09-01

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

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

PubMed

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

2016-12-01

Vitamine D (VD) has important functions in the human brain and may play a role in affective-related disorders. VD receptors are expressed in multiple brain regions associated with depressive disorders. The aim of the preclinical study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0mg/kg/day,s.c., once daily, for 14days) on the depression-like behavior and corticosterone levels in the blood samples following ovariectomy in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E 2 , 0.5μg/rat,s.c., once daily, for 14days). Depression-like behavior and spontaneous locomotor activity were assessed in the forced swimming test (FST) and the open field test (OFT), respectively. The corticosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with cholecalciferol in high dose (5.0mg/kg/day,s.c.) significantly decreased the immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E 2 exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose (5.0mg/kg/day,s.c.) administered alone or together with 17β-E 2 significantly enhanced frequency of grooming for the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E 2 significantly decreased the elevated corticosterone levels in the blood serum of OVX rats following the FST. These results indicate that Cholecalciferol in high dose has a marked antidepressant-like effect in the adult female rats with low levels of estrogen. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ageing introduces a complex pattern of changes in several rat brain transcription factors depending on gender and anatomical localization.

PubMed

Sanguino, Elena; Roglans, Núria; Rodríguez-Calvo, Ricardo; Alegret, Marta; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Laguna, Juan C

2006-04-01

As ageing changes the activity of several transcription factors in the rat cortex, we were interested in determining whether similar changes also appear in the hippocampus of old rats. We determined by electrophoretic gel shift assays the binding activity of nuclear factor kappa B (NFkappaB), activator protein-1 (AP-1), peroxisome proliferator-activated receptor (PPAR), and liver X receptor (LXR) in cortex and hippocampus samples from young (3-month-old), and old (18-month-old) male and female Sprague-Dawley rats. NFkappaB activity increased in old male and female rats, though only in cortex samples, while AP-1 activity decreased only in the cortex and hippocampus of old female animals. LXR activity decreased in all conditions, except in old male cortexes; whereas PPAR activity only decreased in the hippocampus of old female rats. Decreases in AP-1 and PPAR activities restricted to old female rats did not result from an age-related decline in plasma 17beta-estradiol concentration, as their activities did not change in samples obtained from ovariectomized young female rats. Our results indicate that ageing induces a complex pattern of changes in the brain-binding activity of NFkappaB, AP-1, PPAR and LXR, depending on the anatomical origin of the samples (cortex or hippocampus), and the sex of the animals studied.

Mean girls: sex differences in the effects of mild traumatic brain injury on the social dynamics of juvenile rat play behaviour.

PubMed

Mychasiuk, R; Hehar, H; Farran, A; Esser, M J

2014-02-01

Clinical studies indicate that children who experience a traumatic brain injury (TBI) are often the victim of peer rejection, have very few mutual friends, and are at risk for long-term behavioural and social impairments. Owing to the fact that peer play is critical for healthy development, it is possible that the long-term impairments are associated not only with the TBI, but also altered play during this critical period of brain development. This study was designed to determine if social dynamics and juvenile play are altered in rats that experience a mild TBI (mTBI) early in life. Play-fighting behaviours were recorded and analyzed for young male and female Sprague Dawley rats that were given either an mTBI or a sham injury. The study found that the presence of an mTBI altered the play fighting relationship, and the nature of the alterations were dependent upon the sex of the pairing and the injury status of their peers. Sham rats were significantly less likely to initiate play with an mTBI rat, and were more likely to respond to a play initiation from an mTBI rat with an avoidant strategy. This effect was significantly more pronounced in female rats, whereby it appeared that female rats with an mTBI were particularly rejected and most often excluded from play experiences. Male rats with an mTBI learned normal play strategies from their sham peers (when housed in mixed cages), whereas female rats with an mTBI show heightened impairment in these conditions. Play therapy may need to be incorporated into treatment strategies for children with TBI. Copyright © 2013 Elsevier B.V. All rights reserved.

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

PubMed Central

Newson, Penny; Lynch-Frame, Ann; Roach, Rebecca; Bennett, Sarah; Carr, Vaughan; Chahl, Loris A

2005-01-01

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. PMID:16041396

Ovariectomy ameliorates dextromethorphan - induced memory impairment in young female rats

PubMed Central

Jahng, Jeong Won; Cho, Hee Jeong; Kim, Jae Goo; Kim, Nam Youl; Lee, Seoul; Lee, Yil Seob

2006-01-01

We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28–37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17β-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats. PMID:16563229

Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain.

PubMed

Pei, Minjuan; Matsuda, Ken-Ichi; Sakamoto, Hirotaka; Kawata, Mitsuhiro

2006-03-01

Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.

Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov; Johnson, Jerry D.; Hong, S. Peter

Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males followingmore » administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • �

Systemic ICI 182,780 alters the display of sexual behaviors in the female rat.

PubMed

Gardener, H E; Clark, A S

2001-03-01

The present study investigates the effects of the antiestrogen ICI 182,780 (ICI) on the display of sexual behaviors in female rats. ICI 182,780 is a pure anti-estrogen and when given systemically, ICI is thought to act only in the periphery, and is not believed to cross the blood brain barrier. The present study examines the effects of ICI on sexual receptivity and on paced mating behavior following treatment with estradiol benzoate (EB) and progesterone (P) (Experiment 1) or with EB alone (Experiment 2). In Experiment 1, ICI (250.0 microg) did not affect the display of receptivity or paced mating behavior induced by EB and P. In contrast, in Experiment 2 female rats receiving EB alone displayed a decrease in the level of sexual receptivity following treatment with 500.0 and 750.0 microg ICI (but not 250.0 microg ICI). In addition, in Experiment 2 EB-treated female rats receiving 250.0 microg ICI spent more time away from the male rat following an intromission and were more likely to exit from the male compartment following a mount. Last, ICI had potent antiestrogenic effects on vaginal cytology (Experiment 2) and on the uterus (Experiments 1 and 2). The present study supports a role for peripheral estrogen receptors in sexual receptivity and paced mating behavior and suggests that estrogen receptor activation may decrease the aversive sensation associated with sexual stimulation. Copyright 2001 Academic Press.

Polychlorinated biphenyls impair blood-brain barrier integrity via disruption of tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar rats: neuropotential role of quercetin.

PubMed

Selvakumar, K; Prabha, R Lakshmi; Saranya, K; Bavithra, S; Krishnamoorthy, G; Arunakaran, J

2013-07-01

Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances associated with carcinogenic and tumor-promoting effects as well as neurotoxic properties. Reactive oxygen species, which is produced from PCBs, alters blood-brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements and redistribution and disappearance of tight junction proteins (TJPs) like claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and other vegetables, appears to protect brain cells against oxidative stress, a tissue-damaging process associated with Alzheimer's and other neurodegenerative disorders. The aim of this study is to analyze the role of quercetin on oxidative stress markers and transcription of transmembrane and cytoplasmic accessory TJPs on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were divided into the following four groups. Group I: received only vehicle (corn oil) intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received quercetin alone gavage. From the experiment, the levels of hydrogen peroxide, lipid peroxidation and thiobarbituric acid reactive substances were observed to increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and 20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP in rats exposed to PCBs is decreased and is retrieved to the normal level simultaneously in quercetin-treated rats. Hence, quercetin can be used as a preventive medicine to PCBs exposure and prevents neurodegenerative disorders.

Hypergravity induced prolactin surge in female rats

NASA Technical Reports Server (NTRS)

Megory, E.; Oyama, J.

1985-01-01

Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study it is found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats of HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats.

PubMed

Cost, Katherine Tombeau; Lobell, Thomas D; Williams-Yee, Zari N; Henderson, Sherryl; Dohanich, Gary

2014-01-01

Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring. © 2013.

Estradiol promotes the rewarding effects of nicotine in female rats.

PubMed

Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

2016-07-01

It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. Copyright © 2016 Elsevier B.V. All rights reserved.

[Effect of exogenous androgen on structures of sexually dimorphism nucleus in preoptic area and anteroventral periventricular nucleus before sexual differentiation in female rats].

PubMed

Huang, Man-li; Wei, Ning; Hu, Jian-bo; Xu, Yi

2008-09-01

To investigate the effects of androgen on sexually dimorphism nucleus in preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV) before sexual differentiation of the brain in female rats. Neonatal female SD rats (n=12) were randomly divided into two groups: androgen group and control group. Twenty-four hours after birth animals were subjected to intraperitoneal injection of 50 microl of testosterone propionate (TP,10.0 g/L) or aseptic oil as control. The rats were sacrificed 60 days after the injection and the brains were collected for crystal violet staining. LEICA Q Win system was applied in detecting the boundaries of SDN-POA and AVPV, then the volumes of SDN-POA and AVPV were calculated. The volumes of SDN-POA in androgen group were significantly larger than those in control group [(16.77+/-2.68) vs (8.99+/-1.42)mm(3)x10(-3), P<0.01], while the volumes of AVPV in androgen group were significantly smaller than those in control group [(9.14+/-1.16) vs (14.62+/-2.80)mm(3)x10(-3), P<0.01]. Exogenous androgen rendered before sexual differentiation in female rats results in enlargement of SDN-POA volumes and reduction of AVPV.

Juvenile female rats, but not male rats, show renewal, reinstatement, and spontaneous recovery following extinction of conditioned fear.

PubMed

Park, Chun Hui J; Ganella, Despina E; Kim, Jee Hyun

2017-12-01

Anxiety disorders emerge early, and girls are significantly more likely to develop anxiety compared to boys. However, sex differences in fear during development are poorly understood. Therefore, we investigated juvenile male and female rats in the relapse behaviors following extinction of conditioned fear. In all experiments, 18-d-old rats first received three white-noise-footshock pairings on day 1. On day 2, extinction involved 60 white-noise alone trials. In experiment 1, we examined renewal by testing the rats in either the same or different context as extinction on day 3. Male rats did not show renewal, however, female rats showed renewal. Experiment 2 investigated reinstatement by giving rats either a mild reminder footshock or context exposure on day 3. When tested the next day, male rats did not show reinstatement, whereas female rats showed reinstatement. Experiment 3 investigated spontaneous recovery by testing the rats either 1 or 5 d following extinction. Male rats did not show any spontaneous recovery whereas female rats did. Taken together, fear regulation appear to be different in males versus females from early in development, which may explain why girls are more prone to suffer from anxiety disorders compared to boys. © 2017 Park et al.; Published by Cold Spring Harbor Laboratory Press.

Hypoxia-ischemia brain damage disrupts brain cholesterol homeostasis in neonatal rats.

PubMed

Yu, Z; Li, S; Lv, S H; Piao, H; Zhang, Y H; Zhang, Y M; Ma, H; Zhang, J; Sun, C K; Li, A P

2009-08-01

The first 3 weeks of life is the peak time of oligodendrocytes development and also the critical period of cholesterol increasing dramatically in central nervous system in rats. Neonatal hypoxia-ischemia (HI) brain damage happening in this period may disturb the brain cholesterol balance as well as white matter development. To test this hypothesis, postnatal day 7 (P7) Sprague-Dawley rats were subjected to HI insult. Cholesterol concentrations from brain and plasma were measured. White matter integrity was evaluated by densitometric analysis of myelin basic protein (MBP) immunostaining and electron microscopy. Brain TNF-alpha and IL-6 levels were also measured. HI-induced brain cholesterol, but not the plasma cholesterol, levels decreased significantly during the first three days after HI compared with naïve and sham operated rats (p<0.05). Obvious hypomyelination was indicated by marked reductions in MBP immunostaining on both P10 and P14 (p<0.01) and less and thinner myelinated axons were detected on P21 by electron microscopy observation. High expressions of brain TNF-alpha and IL-6 12 h after HI (p<0.05) were also observed. The present work provides evidence that HI insult destroyed brain cholesterol homeostasis, which might be important in the molecular pathology of hypoxic-ischemic white matter injury. Proinflammatory cytokines insulting oligodendrocytes, may cause cholesterol unbalance. Furthermore, specific therapeutic interventions to maintain brain cholesterol balance may be effective for the recovery of white matter function. Georg Thieme Verlag KG Stuttgart New York.

Development of antibodies against the rat brain somatostatin receptor.

PubMed

Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

1992-05-15

Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

Mitochondria, Estrogen and Female Brain Aging

PubMed Central

Lejri, Imane; Grimm, Amandine; Eckert, Anne

2018-01-01

Mitochondria play an essential role in the generation of steroid hormones including the female sex hormones. These hormones are, in turn, able to modulate mitochondrial activities. Mitochondria possess crucial roles in cell maintenance, survival and well-being, because they are the main source of energy as well as of reactive oxygen species (ROS) within the cell. The impairment of these important organelles is one of the central features of aging. In women’s health, estrogen plays an important role during adulthood not only in the estrous cycle, but also in the brain via neuroprotective, neurotrophic and antioxidant modes of action. The hypestrogenic state in the peri- as well as in the prolonged postmenopause might increase the vulnerability of elderly women to brain degeneration and age-related pathologies. However, the underlying mechanisms that affect these processes are not well elucidated. Understanding the relationship between estrogen and mitochondria might therefore provide better insights into the female aging process. Thus, in this review, we first describe mitochondrial dysfunction in the aging brain. Second, we discuss the estrogen-dependent actions on the mitochondrial activity, including recent evidence of the estrogen—brain-derived neurotrophic factor and estrogen—sirtuin 3 (SIRT3) pathways, as well as their potential implications during female aging. PMID:29755342

Age differentially influences estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) gene expression in specific regions of the rat brain.

PubMed

Wilson, Melinda E; Rosewell, Katherine L; Kashon, Michael L; Shughrue, Paul J; Merchenthaler, Istvan; Wise, Phyllis M

2002-03-31

Estradiol's ability to influence neurochemical events that are critical to female reproductive cyclicity and behavior decreases with age. We tested the hypothesis that decreases in estrogen receptor-alpha (ERalpha) and/or ERbeta mRNA explain the brain's declining responsiveness to estradiol. We assessed ERalpha and ERbeta mRNA levels in intact and ovariectomized estradiol-treated rats. ERbeta mRNA was detected in several brain regions and decreased by middle-age in the cerebral cortex and supraoptic nucleus of estradiol-treated rats. ERbeta mRNA levels exhibited a diurnal rhythm in the suprachiasmatic nucleus of young and middle-aged rats and this rhythm was blunted in old rats. We examined ERalpha mRNA in the periventricular preoptic, medial preoptic, ventromedial and arcuate nuclei, and it was decreased only in the periventricular preoptic nucleus of the old rats. In summary, the expression of ERalpha and ERbeta mRNAs is differentially modulated in the aging brain and changes are region specific.

Effects of Different Levels of Calcium Intake on Brain Cell Apoptosis in Fluorosis Rat Offspring and Its Molecular Mechanism.

PubMed

Sun, Yan; Ke, Lulu; Zheng, Xiangren; Li, Tao; Ouyang, Wei; Zhang, Zigui

2017-04-01

The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague-Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3 months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis-related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells.

Oseltamivir and indomethacin reduce the oxidative stress in brain and stomach of infected rats.

PubMed

Guzmán, David Calderón; Herrera, Maribel Ortiz; Brizuela, Norma Osnaya; Mejía, Gerardo Barragán; García, Ernestina Hernández; Olguín, Hugo Juárez; Ruíz, Norma Labra; Peraza, Armando Valenzuela

2018-02-01

The aim of this study was to determine the effect of oseltamivir and indomethacin on lipid peroxidation (LP), GABA levels, and ATPase activity in brain and stomach of normal and infected rats (IR), as novel inflammation model. Female Sprague Dawley rats grouped five each, either in the absence or presence of a live culture of Salmonella typhimurium (S. typh), were treated as follows: group 1 (control), PBS buffer; group 2, oseltamivir (100 mg/kg); group 3, indomethacin (67 μg/rat); group 4, oseltamivir (100 mg/kg) + indomethacin (67 μg/rat). All drugs were given intraperitoneally for 5 days. IR received the same treatments and the brain and stomach of the rats were removed in order to measure levels of GABA, LP, and total ATPase, using validated methods. Levels of GABA increased in stomach and cortex of IR with oseltamivir, but decreased in striatum and cerebellum/medulla oblongata of IR with indomethacin. LP decreased in the three brain regions of IR with oseltamivir. ATPase increased in stomach of IR and non-IR with oseltamivir and in striatum and cerebellum/medulla oblongata of IR with indomethacin. Results suggest that the effect of free radicals produced in an infection and inflammatory condition caused by S. typh could be less toxic by a combination of oseltamivir and indomethacin. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Sex differences in the effect of acute peripheral IL-1β administration on the brain and serum BDNF and VEGF expression in rats.

PubMed

Obuchowicz, Ewa; Nowacka, Marta; Paul-Samojedny, Monika; Bielecka-Wajdman, Anna M; Małecki, Andrzej

2017-02-01

The present study was designed to evaluate, for the first time, the potential sex differences in BDNF and VEGF systems under normal conditions and in response to IL-1β given ip. Peripheral overproduction of this cytokine mediates the pathophysiology of various acute neuroinflammatory states. Until now, the effect of IL-1β on VEGF expression in rat brain structures and its serum level has not been examined. In male and female rats, the BDNF and VEGF mRNA expression, and BDNF level were evaluated in the amygdala, hippocampus, hypothalamus and pituitary gland. The VEGF levels were determined in the pituitary. Serum BDNF and VEGF levels were also measured. The pituitary BDNF mRNA, and BDNF and VEGF levels were higher in females than in male rats whereas in males, the BDNF levels were higher in the other brain structures. The serum BDNF concentration was similar in both groups but VEGF levels were enhanced in females. Following IL-1β (50μg/kg ip.) administration, a higher serum IL-1β level was detected in females than in males. In male rats, IL-1β decreased BDNF mRNA in all the brain structures, except for the pituitary, and VEGF mRNA in the amygdala. In opposite, IL-1β challenge in females increased the pituitary VEGF mRNA and serum BDNF and VEGF levels. These results suggest that in females BDNF and VEGF may play a more important role in the pituitary function. In males, amygdala trophic system seems to be especially sensitive to the enhanced peripheral IL-1β production. Our findings point to the need to consider sex-related differences to be able to draw reliable conclusions about changes in BDNF and VEGF levels during inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Central endogenous angiotensin-(1-7) protects against aldosterone/NaCl-induced hypertension in female rats.

PubMed

Xue, Baojian; Zhang, Zhongming; Johnson, Ralph F; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

2013-09-01

In comparison to male rodents, females are protected against angiotensin (ANG) II- and aldosterone (Aldo)-induced hypertension. However, the mechanisms underlying this protective effect are not well understood. ANG-(1-7) is formed from ANG II by angiotensin-converting enzyme 2 (ACE2) and has an antihypertensive effect in the central nervous system (CNS). The present study tested the hypothesis that central ANG-(1-7) plays an important protective role in attenuating the development of Aldo/NaCl-hypertension in female rats. Systemic infusion of Aldo into intact female rats with 1% NaCl as their sole drinking fluid resulted in a slight increase in blood pressure (BP). Intracerebroventricular (icv) infusion of A-779, an ANG-(1-7) receptor (Mas-R) antagonist, significantly augmented the pressor effects of Aldo/NaCl. In contrast, systemic Aldo/NaCl induced a significant increase in BP in ovariectomized (OVX) female rats, and central infusion of ANG-(1-7) significantly attenuated this Aldo/NaCl pressor effect. The inhibitory effect of ANG-(1-7) on the Aldo/NaCl pressor effect was abolished by concurrent infusion of A-779. RT-PCR analyses showed that there was a corresponding change in mRNA expression of several renin-angiotensin system components, estrogen receptors and an NADPH oxidase subunit in the lamina terminalis. Taken together these results suggest that female sex hormones regulate an antihypertensive axis of the brain renin-angiotensin system involving ACE2/ANG-(1-7)/Mas-R that plays an important counterregulatory role in protecting against the development of Aldo/NaCl-induced hypertension.

Sexual dimorphism in relations of blood growth-hormone levels to body and brain weights in newborn rats.

PubMed

Elalmis, Derya Deniz; Tan, Uner

2007-12-01

The growth promoting effects of growth hormone (GH) are well-known. However, the studies in this respect did not consider the sexual dimorphism. The adverse--growth limiting--GH effects were also reported in human newborns (see Tan, 1992, 1995; Tan et al., 1998). A similar study was replicated in the newborn rat pups in the present work. The serum GH level, body weight, body height, right- and left-brain weights were measured just after birth in rat pups. The relations of the serum GH levels to the bodily measurements were found to be sexually dimorphic. Namely, there were no significant correlations between the serum GH levels and the body size (weight and height) in males, whereas there were inverse relations between these parameters in females. The GH level negatively linearly related to the right-, left-, and right- minus left-brain weights in females, whereas only the right-brain weight positively linearly correlated with the serum GH level, the right- minus left-brain weight being also positively linearly correlated with the serum GH level in males. The results suggested that the sexual dimorphism should be taken into consideration in studies concerning the global GH effects. The relation of the serum GH level to the right-left brain asymmetry, also sexually dimorphic, suggests a role of GH in cerebral lateralization.

An automatic rat brain extraction method based on a deformable surface model.

PubMed

Li, Jiehua; Liu, Xiaofeng; Zhuo, Jiachen; Gullapalli, Rao P; Zara, Jason M

2013-08-15

The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images. Copyright © 2013 Elsevier B.V. All rights reserved.

Artificial selection on male genitalia length alters female brain size.

PubMed

Buechel, Séverine D; Booksmythe, Isobel; Kotrschal, Alexander; Jennions, Michael D; Kolm, Niclas

2016-11-30

Male harassment is a classic example of how sexual conflict over mating leads to sex-specific behavioural adaptations. Females often suffer significant costs from males attempting forced copulations, and the sexes can be in an arms race over male coercion. Yet, despite recent recognition that divergent sex-specific interests in reproduction can affect brain evolution, sexual conflict has not been addressed in this context. Here, we investigate whether artificial selection on a correlate of male success at coercion, genital length, affects brain anatomy in males and females. We analysed the brains of eastern mosquitofish (Gambusia holbrooki), which had been artificially selected for long or short gonopodium, thereby mimicking selection arising from differing levels of male harassment. By analogy to how prey species often have relatively larger brains than their predators, we found that female, but not male, brain size was greater following selection for a longer gonopodium. Brain subregion volumes remained unchanged. These results suggest that there is a positive genetic correlation between male gonopodium length and female brain size, which is possibly linked to increased female cognitive ability to avoid male coercion. We propose that sexual conflict is an important factor in the evolution of brain anatomy and cognitive ability. © 2016 The Author(s).

Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

PubMed

Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

2014-10-01

Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neonatal handling and reproductive function in female rats.

PubMed

Gomes, C M; Raineki, C; Ramos de Paula, P; Severino, G S; Helena, C V V; Anselmo-Franci, J A; Franci, C R; Sanvitto, G L; Lucion, A B

2005-02-01

Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis.

Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

PubMed

Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

2018-07-02

Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential Behavioral and Biochemical Responses to Caffeine in Male and Female Rats from a Validated Model of Attention Deficit and Hyperactivity Disorder.

PubMed

Nunes, Fernanda; Pochmann, Daniela; Almeida, Amanda Staldoni; Marques, Daniela Melo; Porciúncula, Lisiane de Oliveira

2018-03-20

Epidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3 g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats-SHR). Hyperlocomotion, recognition, and spatial memory disturbances were observed in adolescent SHR rats from both sexes. However, females showed lack of habituation and worsened spatial memory. Although caffeine was effective against recognition memory impairment in both sexes, spatial memory was recovered only in female SHR rats. Besides, female SHR rats showed exacerbated hyperlocomotion after caffeine treatment. SHR rats from both sexes presented increases in the BDNF, truncated and phospho-TrkB receptors and also phospho-CREB levels in the hippocampus. Caffeine normalized BDNF in males and truncated TrkB receptor at both sexes. These findings provide insight into the potential of caffeine against fully cognitive impairment displayed by females in the ADHD model. Besides, our data revealed that caffeine intake since childhood attenuated behavioral alterations in the ADHD model associated with changes in BDNF and TrkB receptors in the hippocampus.

Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

PubMed

Singh, Harpal; Kaur, Taranjeet; Manchanda, Shaffi; Kaur, Gurcharan

2017-08-01

Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

Hypobaric Hypoxia Regulates Brain Iron Homeostasis in Rats.

PubMed

Li, Yaru; Yu, Peng; Chang, Shi-Yang; Wu, Qiong; Yu, Panpan; Xie, Congcong; Wu, Wenyue; Zhao, Baolu; Gao, Guofen; Chang, Yan-Zhong

2017-06-01

Disruption of iron homeostasis in brain has been found to be closely involved in several neurodegenerative diseases. Recent studies have reported that appropriate intermittent hypobaric hypoxia played a protective role in brain injury caused by acute hypoxia. However, the mechanisms of this protective effect have not been fully understood. In this study, Sprague-Dawley (SD) rat models were developed by hypobaric hypoxia treatment in an altitude chamber, and the iron level and iron related protein levels were determined in rat brain after 4 weeks of treatment. We found that the iron levels significantly decreased in the cortex and hippocampus of rat brain as compared to that of the control rats without hypobaric hypoxia treatment. The expression levels of iron storage protein L-ferritin and iron transport proteins, including transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin1 (FPN1), were also altered. Further studies found that the iron regulatory protein 2 (IRP2) played a dominant regulatory role in the changes of iron hemostasis, whereas iron regulatory protein 1 (IRP1) mainly acted as cis-aconitase. These results, for the first time, showed the alteration of iron metabolism during hypobaric hypoxia in rat models, which link the potential neuroprotective role of hypobaric hypoxia treatment to the decreased iron level in brain. This may provide insight into the treatment of iron-overloaded neurodegenerative diseases. J. Cell. Biochem. 118: 1596-1605, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease.

PubMed

Bosoi, Cristina R; Zwingmann, Claudia; Marin, Helen; Parent-Robitaille, Christian; Huynh, Jimmy; Tremblay, Mélanie; Rose, Christopher F

2014-03-01

The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis. Six-week bile-duct ligated (BDL) rats were injected with (13)C-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using (13)C nuclear magnetic resonance spectroscopy (NMR). Total brain lactate, glutamine, and osmolytes were measured using (1)H NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and brain edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor). Significant increases in de novo synthesis of lactate (1.6-fold, p<0.001) and glutamine (2.2-fold, p<0.01) were demonstrated in the brains of BDL rats vs. SHAM-operated controls. Moreover, a decrease in cerebral myo-inositol (p<0.001), with no change in taurine, was found in the presence of brain edema in BDL rats vs. controls. BDL rats treated with either AST-120 or DCA showed attenuation in brain edema and brain lactate. These two treatments did not lead to similar reductions in brain glutamine. Increased brain lactate, and not glutamine, is a primary player in the pathogenesis of brain edema in CLD. In addition, alterations in the osmoregulatory response may also be contributing factors. Our results suggest that inhibiting lactate synthesis is a new potential target for the treatment of HE. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effects of sex steroids on muscarinic sties in the rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Dahan, M.I.

1986-03-01

The level of binding sites for (/sup 3/H)scopolamine in the rat hypothalamus and amygdala (but not elsewhere in the brain) is modified by hormonal status. In females, there is an inverse relation between the level of sites and estrogen (E/sub 2/) and progesterone (P) concentration. Binding is high in metoestrous (Met) and in ovariectomized (Ovx) animals but low in proestrous (Pro). Hormone replacement in ovariectomized animals lowers the level of the sites. Castration (Cast) of males reduces the level of sites but subsequent testosterone (T) treatment restores normal levels. The results support a role of hormones in sexual behavior viamore » alteration in levels of muscarinic receptors: male hormone increases and female hormones decrease receptor levels.« less

Effect of sibutramine on 5-hydroxyindole acetic acid levels and selected oxidative biomarkers on brain regions of female rats in the presence of zinc.

PubMed

Guzmán, David C; García, Ernestina H; Mejía, Gerardo B; Olguín, Hugo J; Jiménez, Francisca T; Soto, Erick B; Del Angel, Daniel S; Aparicio, Liliana C

2012-05-01

A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 μg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

PubMed

Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

2017-03-01

Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

Resistance exercise reduces memory impairment induced by monosodium glutamate in male and female rats.

PubMed

Araujo, Paulo Cesar Oliveira; Quines, Caroline Brandão; Jardim, Natália Silva; Leite, Marlon Regis; Nogueira, Cristina Wayne

2017-07-01

What is the central question of this study? Monosodium glutamate causes cognitive impairment. Does resistance exercise improve the performance of rats treated with monosodium glutamate? What is the main finding and its importance? Resistance exercise is effective against monosodium glutamate-induced memory impairment in male and female rats. Monosodium glutamate (MSG), a flavour enhancer in diets, causes cognitive impairment in rodents. Exercise has been reported to protect against impairment of memory in humans. In this study, we investigated whether resistance exercise improves the performance of male and female rats treated with MSG in tests of memory and motor co-ordination. Wistar rats received MSG [4 g (kg body weight) -1  day -1 , s.c.] from postnatal day 1 to 10. At postnatal day 60, the animals started a resistance exercise protocol in an 80 deg inclined vertical ladder apparatus and performed it during 7 weeks. Rats performed object recognition and location memory tests. Resistance exercise reduced impairment in motor co-ordination of male and female rats treated with MSG. Resistance exercise was effective against the decrease in exploratory preference in the long-term recognition memory for novel objects of male rats treated with MSG. In MSG-treated female rats, resistance exercise was effective against the decrease in exploratory preference in the novel object location test. The exploratory preference of female rats in the long-term recognition memory test was similar in all groups. The short-term memory was not altered by MSG or resistance exercise in male and female rats. This study demonstrates that MSG affected the memory of male and female rats in different ways. Resistance exercise was effective against the decrease in recognition for male rats and in location memory for female rats treated with MSG. This report demonstrates the beneficial effects of resistance exercise against the prejudice of motor condition and impairment of memory induced

Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum) on the brain development of newborn rats.

PubMed

Lenzi Almeida, K C; Teles Boaventura, G; Guzmán Silva, M A

2011-01-01

The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n=6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats.

Effects of corticosterone on contextual fear consolidation in intact and ovariectomized female rats.

PubMed

Kashefi, Adel; Rashidy-Pour, Ali

2014-10-01

Previous studies have shown that post-training administration of glucocorticoids enhances memory consolidation in male rats, but theirs effects on female rats are not known. Thus, this study was conducted to examine the effects of corticosterone (CORT) on contextual fear memory consolidation in intact and ovariectomized (OVX) female rats. In Experiment 1, post-training administration of CORT (0.3, 3, and 10 mg/kg) to OVX female rats impaired memory consolidation at a 0.3 mg dose of CORT. In Experiment 2, post-training injection of CORT (0.3 mg/kg) to female rats in proestrus stage (when the levels of estrogens are highest) enhances and in the estrus stage (when the levels of estrogens are lowest) impaired memory retention. In Experiment 3, OVX female rats injected with CORT (0.3 mg/kg) and one of the three doses of 17β-estradiol (1, 10 or 100 μg/kg) following training. 48-h memory retention test indicated that CORT enhanced memory retention in OVX female rats that received concurrent injection of 10 or 100 μg doses of 17β-estradiol. These findings indicate that cognitive effects of CORT in female rats can be modulated with the plasma levels of estrogens: when the levels of estrogens are low, corticosterone has a negative effect, while when the levels of estrogens are high; the corticosterone has a positive enhancing effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Biological sex influences learning strategy preference and muscarinic receptor binding in specific brain regions of prepubertal rats.

PubMed

Grissom, Elin M; Hawley, Wayne R; Hodges, Kelly S; Fawcett-Patel, Jessica M; Dohanich, Gary P

2013-04-01

According to the theory of multiple memory systems, specific brain regions interact to determine how the locations of goals are learned when rodents navigate a spatial environment. A number of factors influence the type of strategy used by rodents to remember the location of a given goal in space, including the biological sex of the learner. We recently found that prior to puberty male rats preferred a striatum-dependent stimulus-response strategy over a hippocampus-dependent place strategy when solving a dual-solution task, while age-matched females showed no strategy preference. Because the cholinergic system has been implicated in learning strategy and is known to be sexually dimorphic prior to puberty, we explored the relationship between learning strategy and muscarinic receptor binding in specific brain regions of prepubertal males and female rats. We confirmed our previous finding that at 28 days of age a significantly higher proportion of prepubertal males preferred a stimulus-response learning strategy than a place strategy to solve a dual-solution visible platform water maze task. Equal proportions of prepubertal females preferred stimulus-response or place strategies. Profiles of muscarinic receptor binding as assessed by autoradiography varied according to strategy preference. Regardless of biological sex, prepubertal rats that preferred stimulus-response strategy exhibited lower ratios of muscarinic receptor binding in the hippocampus relative to the dorsolateral striatum compared to rats that preferred place strategy. Importantly, much of the variance in this ratio was related to differences in the ventral hippocampus to a greater extent than the dorsal hippocampus. The ratios of muscarinic receptors in the hippocampus relative to the basolateral amygdala also were lower in rats that preferred stimulus-response strategy over place strategy. Results confirm that learning strategy preference varies with biological sex in prepubertal rats with males

Characterization of biliary conjugates of 4,4'-methylenedianiline in male versus female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Kan; Cole, Richard B.; Santa Cruz, Vicente

2008-10-15

4,4'-Methylenedianiline (4,4'-diaminodiphenylmethane; DAPM) is an aromatic diamine used in the production of numerous polyurethane foams and epoxy resins. Previous studies in rats revealed that DAPM initially injures biliary epithelial cells of the liver, that the toxicity is greater in female than in male rats, and that the toxic metabolites of DAPM are excreted into bile. Since male and female rats exhibit differences in the expression of both phase I and phase II enzymes, our hypothesis was that female rats either metabolize DAPM to more toxic metabolites or have a decreased capacity to conjugate metabolites to less toxic intermediates. Our objectivemore » was thus to isolate, characterize, and quantify DAPM metabolites excreted into bile in both male and female bile duct-cannulated Sprague Dawley rats. The rats were gavaged with [{sup 14}C]-DAPM, and the collected bile was subjected to reversed-phase HPLC with radioisotope detection. Peaks eluting from HPLC were collected and analyzed using electrospray MS and NMR spectroscopy. HPLC analysis indicated numerous metabolites in both sexes, but male rats excreted greater amounts of glutathione and glucuronide conjugates than females. Electrospray MS and NMR spectra of HPLC fractions revealed that the most prominent metabolite found in bile of both sexes was a glutathione conjugate of an imine metabolite of a 4'-nitroso-DAPM. Seven other metabolites were identified, including acetylated, cysteinyl-glycine, glutamyl-cysteine, glycine, and glucuronide conjugates. While our prior studies demonstrated increased covalent binding of DAPM in the liver and bile of female compared to male rats, in these studies, SDS-PAGE with autoradiography revealed 4-5 radiolabeled protein bands in the bile of rats treated with [{sup 14}C]-DAPM. In addition, these bands were much more prominent in female than in male rats. These studies thus suggest that a plausible mechanism for the increased sensitivity of female rats to DAPM toxicity

Reproductive effects of Ficus asperifolia (Moraceae) in female rats.

PubMed

Watcho, Pierre; Ngadjui, Esther; Alango, Nkeng-Efouet P; Benoît, Nguelefack T; Kamanyi, Albert

2009-03-01

The reproductive effects of Ficus asperifolia in female rats were investigated in the present study. Sperm-positive adult female rats were orally administered (P.O.) either the aqueous and methanol extracts of Ficus asperifolia (100 and 500mg/kg), distilled water (10ml/kg) or 5%Tween 80 (10ml/kg) for seven days. On day 10 of pregnancy, the implantation sites were recorded. In the fertility study, adult female rats received the same test substances for 21 days and, the fertility index and litter size determined. In the uterotrophic test, normal and ovariectomized immature rats were treated for seven days with the dry extract of Ficus asperifolia (100 and 500mg/kg) in the absence and presence of 17ȃ-estradiol benzoate 1µg/animal/day, s.c. On day 8, the uterine growth index was measured. Results of the study showed a significant increase (p<0.05) in the implantation sites and litter size of animals receiving 100mg/kg of the aqueous extract of Ficus asperifolia. In the estrogenic assay, normal immature rats were sensitive to the treatment with Ficus asperifolia than the ovariectomized ones. Our results give added scientific support to the popular use of Ficus asperifolia in the treatment of some cases of women's sterility/infertility related problems.

Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

PubMed

Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

2017-07-01

In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (p<0.05, t-test). Righting reflex was delayed in offspring from HFD-fed mothers compared to the Chow mothers. The Chow-HI pups showed a loss in ipsilateral brain tissue, while the HFD-HI group had significantly greater loss. No significant difference was detected in brain volume between the HFD-C and Chow-C pups. When analysed on a per litter basis, the size of the injury was significantly correlated with maternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of

[Expression of c-jun protein after experimental rat brain concussion].

PubMed

Wang, Feng; Li, Yong-hong

2010-02-01

To observe e-jun protein expression after rat brain concussion and explore the forensic pathologic markers following brain concussion. Fifty-five rats were randomly divided into brain concussion group and control group. The expression of c-jun protein was observed by immunohistochemistry. There were weak positive expression of c-jun protein in control group. In brain concussion group, however, some neutrons showed positive expression of c-jun protein at 15 min after brain concussion, and reach to the peak at 3 h after brain concussion. The research results suggest that detection of c-jun protein could be a marker to determine brain concussion and estimate injury time after brain concussion.

Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

PubMed

Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

2018-05-01

Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

Infarct size is increased in female post-MI rats treated with rapamycin.

PubMed

Lajoie, Claude; El-Helou, Viviane; Proulx, Cindy; Clément, Robert; Gosselin, Hugues; Calderone, Angelino

2009-06-01

Rapamycin represents a recognized drug-based therapeutic approach to treat cardiovascular disease. However, at least in the female heart, rapamycin may suppress the recruitment of putative signalling events conferring cardioprotection. The present study tested the hypothesis that rapamycin-sensitive signalling events contributed to the cardioprotective phenotype of the female rat heart after an ischemic insult. Rapamycin (1.5 mg/kg) was administered to adult female Sprague-Dawley rats 24 h after complete coronary artery ligation and continued for 6 days. Rapamycin abrogated p70S6K phosphorylation in the left ventricle of sham rats and the noninfarcted left ventricle (NILV) of 1-week postmyocardial-infarcted (MI) rats. Scar weight (MI 0.028 +/- 0.006, MI+rapamycin 0.064 +/- 0.004 g) and surface area (MI 0.37 +/- 0.08, MI+rapamycin 0.74 +/- 0.03 cm2) were significantly larger in rapamycin-treated post-MI rats. In the NILV of post-MI female rats, rapamycin inhibited the upregulation of eNOS. Furthermore, the increased expression of collagen and TGF-beta3 mRNAs in the NILV were attenuated in rapamycin-treated post-MI rats, whereas scar healing was unaffected. The present study has demonstrated that rapamycin-sensitive signalling events were implicated in scar formation and reactive fibrosis. Rapamycin-mediated suppression of eNOS and TGF-beta3 mRNA in post-MI female rats may have directly contributed to the larger infarct and attenuation of the reactive fibrotic response, respectively.

In-vivo imaging of the morphology and blood perfusion of brain tumours in rats with UHR-OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bizheva, Kostadinka; Tan, Bingyao; Fisher, Carl J.; Mason, Erik; Lilge, Lothar D.

2017-02-01

Brain tumors are characterized with morphological changes at cellular level such as enlarged, non-spherical nuclei, microcalcifications, cysts, etc., and are highly vascularized. In this study, two research-grade optical coherence tomography (OCT) systems operating at 800 nm and 1060 nm with axial resolution of 0.95 µm and 3.5 µm in biological tissue respectively, were used to image in vivo and ex vivo the structure of brain tumours in rats. Female Fischer 344 rats were used for this study, which has received ethics clearance by the Animal Research Ethics Committees of the University of Waterloo and the University Health Network, Toronto. Brain tumours were induced by injection of rat brain cancer cell line (RG2 glioma) through a small craniotomy. Presence of brain tumours was verified by MRI imaging on day 7 post tumour cells injection. The in vivo OCT imaging session was conducted on day 14 of the study with the 1060 nm OCT system and both morphological OCT, Doppler OCT and OMAG images were acquired from the brain tumour and the surrounding healthy brain tissue. After completion of the imaging procedure, the brains were harvested, fixed in formalin and reimaged after 2 weeks with the 800 nm OCT system. The in vivo and ex vivo OCT morphological images were correlated with H and E histology. Results from this study demonstrate that UHR-OCT can distinguish between healthy and cancerous brain tissue based on differences in structural and vascular pattern.

Analysis of c-Fos induction in response to social interaction in male and female Fisher 344 rats.

PubMed

Perkins, Amy E; Woodruff, Elizabeth R; Chun, Lauren E; Spencer, Robert L; Varlinskaya, Elena; Deak, Terrence

2017-10-01

Sex differences in the expression of social behavior are typically apparent in adolescent and adult rats. While the neurobiology underlying juvenile social play behavior has been well characterized, less is known about discrete brain regions involved in adult responsiveness to a same sex peer. Furthermore, whether adult males and females differ in their responsiveness to a social interaction in terms of neuronal activation indexed via immediate early gene (IEG) expression remains to be determined. Thus, the present study was designed to identify key sites relevant to the processing of sensory stimuli (generally) or social stimuli (specifically) after brief exposure to a same-sex social partner by assessing IEG expression. Four-month-old male and female Fisher (F) 344 rats (N=38; n=5-8/group) were either left undisturbed in their home cage as controls (HCC), exposed to a testing context alone for 30min (CXT), or were placed in the context for 20min and then allowed to socially interact (SI) with a sex-matched conspecific for 10min. Females demonstrated greater levels of social behavior, relative to males. Analysis of c-Fos induction revealed that females exhibited greater c-Fos expression in the prefrontal cortex, regardless of condition. In many brain regions, induction was similar in the CXT and SI groups. However, in the bed nucleus of the stria terminalis (BNST), females exhibited greater c-Fos induction in response to the social interaction relative to their male counterparts, indicating a sex difference in responsivity to social stimuli. Taken together, these data suggest that the BNST is a sexually dimorphic region in terms of activation in response to social stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats.

PubMed

Karaismailoglu, S; Tuncer, M; Bayrak, S; Erdogan, G; Ergun, E L; Erdem, A

2017-08-01

Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3 g/L) or high (0.8 g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.

Soyo-san reduces depressive-like behavior and proinflammatory cytokines in ovariectomized female rats

PubMed Central

2014-01-01

Background Soyo-san is a traditional oriental medicinal formula, a mixture of 9 crude drugs, and it has been clinically used for treating mild depressive disorders. The role of pro- and anti-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. In the present study, we detected the antidepressant effect of soyo-san in the ovariectomized and repeated stressed female rats. Methods This study was designed to evaluate the antidepressant-like effect of soyo-san on the forced swimming test (FST). The rats were randomly divided into the following groups: the nonoperated and nonstressed group (non-op), the nonoperated and stressed group (non-op + ST), the ovariectomized and stress group (OVX) and sham operated and stressed group (sham), the ovariectomized and stressed group (OVX + ST), the ovariectomized, stressed and soyo-san 100 mg/kg treated group (SOY100) and the ovariectomized, stressed and soyo-san 400 mg/kg treated group (SOY400). The rats were exposed to immobilization stress (IMO) for 14day (2 h/14day), and soyo-san (100 mg/kg and 400 mg/kg) was administrated during the same time. In the same animals, the levels of corticosterone and interleukin-1-beta (IL-1β) were examined in the serum. Also, the change of IL-1β expression in brain regions was examined after behavior test. Results In the FST, the lower dose (100 mg/kg) of extract was effective in reducing immobility, along with an increase in swimming time. The serum levels of corticosterone and IL-1β in the SOY groups were significantly lower than those in the control group. In the brain, the expression of IL-1β positive neurons in the control group were significantly increased in the paraventricular nucleus (PVN) and hippocampus compared to the non-op. However, soyo-san groups significantly reduced the IL-1β-ir neurons in the PVN and hippocampal regions compared to the control. Conclusion The present results demonstrated that soyo

Brain glucose content in fetuses of ethanol-fed rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pullen, G.; Singh, S.P.; Snyder, A.K.

1986-03-01

The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4more » and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.« less

Hydrophilic solute transport across the rat blood-brain barrier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucchesi, K.J.

1987-01-01

Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB)more » was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.« less

Quercetin protects rat cortical neurons against traumatic brain injury.

PubMed

Du, Guoliang; Zhao, Zongmao; Chen, Yonghan; Li, Zonghao; Tian, Yaohui; Liu, Zhifeng; Liu, Bin; Song, Jianqiang

2018-06-01

Previous studies have demonstrated that traumatic brain injury (TBI) may cause neurological deficits and neuronal cell apoptosis. Quercetin, one of the most widely distributed flavonoids, possesses anti‑inflammatory, anti‑blood coagulation, anti‑ischemic and anti‑cancer activities, and neuroprotective effects in the context of brain injury. The purpose of the present study was to investigate the neuroprotective effects of quercetin in TBI. A total of 75 rats were randomly arranged into 3 groups as follows: Sham group (Sham); TBI group (TBI); and TBI + quercetin group (Que). Brain edema was evaluated by analysis of brain water content. The neurobehavioral status of the rats was evaluated by Neurological Severity Scoring. Immunohistochemical and western blot analyses were used to measure the expression of certain proteins. The results of the present study demonstrated that post‑TBI administration of quercetin may attenuate brain edema, in addition to improving motor function in rats. Additionally, quercetin caused a marked inhibition of extracellular signal‑regulated kinase 1/2 phosphorylation and activated Akt serine/threonine protein kinase phosphorylation, which may result in attenuation of neuronal apoptosis. The present study provided novel insights into the mechanism through which quercetin may exert its neuroprotective activity in a rat model of TBI.

Effect of progesterone on the expression of GABA(A) receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere.

PubMed

Andrade, Susie; Arbo, Bruno D; Batista, Bruna A M; Neves, Alice M; Branchini, Gisele; Brum, Ilma S; Barros, Helena M T; Gomez, Rosane; Ribeiro, Maria Flavia M

2012-12-01

Progesterone is a neuroactive hormone with non-genomic effects on GABA(A) receptors (GABA(A)R). Changes in the expression of GABA(A)R subunits are related to depressive-like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABA(A)R α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg⁻¹) or vehicle, during two complete female estrous cycles (8-10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive-like behaviors and GABA(A)R α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA(A)R γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA(A) system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA(A) R α1 subunit expression in the right prefrontal cortex of female rats. Copyright © 2012 John Wiley & Sons, Ltd.

Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, K.L.; Tyce, G.M.

1983-04-01

The metabolism of glucose in brains during sustained hypoglycemia was studied. (U-/sup 14/C)Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. Inmore » the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia.« less

Contingency Training Alters Neurobiological Components of Emotional Resilience in Male and Female Rats.

PubMed

Kent, M; Scott, S; Lambert, S; Kirk, E; Terhune-Cotter, B; Thompson, B; Neal, S; Dozier, B; Bardi, M; Lambert, K

2018-06-19

Prior research with a rat model of behavioral therapy [i.e., effort-based reward (EBR) contingency training] suggests that strengthened associations between physical effort and desired outcomes enhance neurobiological indices of resilience. In the current study, male and female Long-Evans rats were exposed to either six weeks of EBR training or noncontingent training prior to 10 days of exposure to chronic unpredictable stress (CUS). Subsequently, all animals were exposed to a problem-solving task and then trained in a spatial learning/foraging task, the Dry Land Maze (DLM). Following habituation training and test trials, rats were assessed in a probe trial that generated a prediction error (cognitive uncertainty). Results indicated that, during CUS exposure, contingency-training enhanced dehydroepiandrosterone/corticosterone ratios (consistent with healthier stress responses), especially in male rats. Additionally, contingency training increased exploratory behaviors in the probe trial as well as differentially influenced on-task problem-solving performance in males and females. Following the probe trial, brains were exposed to histological analyses to determine the effects of sex and contingency training on various neurobiological markers. Contingency training decreased BDNF-immunoreactivity (ir) in the hippocampus CA1 and lateral habenula, implicating differential neuroplasticity responses in the training groups. Further, coordinated fos-ir activation in areas associated with emotional resilience (i.e., motivation-regulation) was observed in contingent-trained animals. In sum, the current findings confirm that behavioral training is associated with neurobiological markers of emotional resilience; however, further assessments are necessary to more accurately determine the therapeutic potential for the EBR contingency training model. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Rats exposed to 2.45GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3.

PubMed

Varghese, Rini; Majumdar, Anuradha; Kumar, Girish; Shukla, Amit

2018-03-01

In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

PubMed

Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

2014-01-01

The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Rapid changes in brain aromatase activity in the female quail brain following expression of sexual behaviour.

PubMed

de Bournonville, C; Ball, G F; Balthazart, J; Cornil, C A

2017-11-01

In male quail, oestrogens produced in the brain (neuro-oestrogens) exert a dual action on male sexual behaviour: they increase sexual motivation within minutes via mechanisms activated at the membrane but facilitate sexual performance by slower, presumably nuclear-initiated, mechanisms. Recent work indicates that neuro-oestrogens are also implicated in the control of female sexual motivation despite the presence of high circulating concentrations of oestrogens of ovarian origin. Interestingly, aromatase activity (AA) in the male brain is regulated in time domains corresponding to the slow "genomic" and faster "nongenomic" modes of action of oestrogens. Furthermore, rapid changes in brain AA are observed in males after sexual interactions with a female. In the present study, we investigated whether similar rapid changes in brain AA are observed in females allowed to interact sexually with males. A significant decrease in AA was observed in the medial preoptic nucleus after interactions that lasted 2, 5 or 10 minutes, although this decrease was no longer significant after 15 minutes of interaction. In the bed nucleus of the stria terminalis, a progressive decline of average AA was observed between 2 and 15 minutes, although it never reached statistical significance. AA in this nucleus was, however, negatively correlated with the sexual receptivity of the female. These data indicate that sexual interactions affect brain AA in females as in males in an anatomically specific manner and suggest that rapid changes in brain oestrogens production could also modulate female sexual behaviour. © 2017 British Society for Neuroendocrinology.

Laser scattering by transcranial rat brain illumination

NASA Astrophysics Data System (ADS)

Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.

2012-06-01

Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.

COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats.

PubMed

Günther, Mattias; Plantman, Stefan; Davidsson, Johan; Angéria, Maria; Mathiesen, Tiit; Risling, Mårten

2015-04-01

Traumatic brain injury is followed by secondary neuronal degeneration, largely dependent on an inflammatory response. This response is probably gender specific, since females are better protected than males in experimental models. The reasons are not fully known. We examined aspects of the inflammatory response following experimental TBI in male and female rats to explore possible gender differences at 24 h and 72 h after trauma, times of peak histological inflammation and neuronal degeneration. A penetrating brain injury model was used to produce penetrating focal TBI in 20 Sprague-Dawley rats, 5 males and 5 females for each time point. After 24 and 72 h the brains were removed and subjected to in situ hybridization and immunohistochemical analyses for COX-2, iNOS, osteopontin, glial fibrillary acidic protein, 3-nitrotyrosine, TUNEL and Fluoro-Jade. COX-2 mRNA and protein levels were increased in the perilesional area compared to the uninjured contralateral side and significantly higher in males at 24 h and 72 h (p < 0.05). iNOS mRNA was significantly increased in females at 24 h (p < 0.05) although protein was not. TUNEL was increased in male rats after 24 h (p < 0.05). Glial fibrillary acidic protein, osteopontin, 3-nitrotyrosine and Fluoro-Jade stained degenerating neurons were increased in the perilesional area, showing no difference between genders. COX-2 regulation differed between genders after TBI. The increased COX-2 expression in male rats correlated with increased apoptotic cell death detected by increased TUNEL staining at 24 h, but not with neuronal necrosis measured by Flouro-Jade. Astrogliosis and microgliosis did not differ, confirming a comparable level of trauma. The gender-specific trait of the secondary inflammatory response may be connected to prostaglandin regulation, which may partially explain gender variances in outcome after TBI.

Brain activation-based sexual orientation in female-to-male transsexuals.

PubMed

Kim, T-H; Kim, G-W; Kim, S-K; Jeong, G-W

2016-01-01

This study was performed to identify the sexual orientation in association with brain activation pattern in response to visual erotic stimuli in female-to-male (FtM) transsexuals by using functional magnetic resonance imaging (fMRI). Eleven FtM transsexuals who have had sex-reassignment surgery to alter their natal bodies with the gender-identity disorder were participated. Brain activation for sexual orientation was induced by visual stimuli with female and male erotic nude pictures compared with emotionally-neutral pictures. During viewing the erotic female pictures, the brain areas dominantly activated consist of the superior frontal gyrus, supplementary motor area, anterior/median cingulate gyri and hypothalamus, whereas during viewing male pictures, the brain areas with predominant activities were the middle frontal gyrus, precentral gyrus, middle temporal gyrus, fusiform gyrus, angular gyrus, precuneus, superior/middle occipital gyri, cerebellar cortex and vermis. These findings demonstrate that the brain activation patterns induced by viewing male or female erotic pictures show some correlation to the sexual orientation opposite to the genetic sex in FtM transsexuals. This study would be helpful to understand the neural mechanism associated with visual sexual arousal in patients with gender disorder.

Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats.

PubMed

Feng, Yangzheng; Fratkins, Jonathan D; LeBlanc, Michael H

2004-01-19

Tamoxifen, an estrogen receptor modulator, is neuroprotective in adult rats. Does tamoxifen reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of hypoxia (8% oxygen). Tamoxifen (10 mg/kg) or vehicle was given i.p. 5 min prior to hypoxia, or 5 min after reoxygenation, with a second dose given 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere 22 days following hypoxia and gross and microscopic morphology. Tamoxifen pre-treatment reduced brain weight loss from 21.5+/-4.0% in vehicle pups (n=27) to 2.6+/-2.5% in the treated pups (n=22, P<0.05). Treatment 5 min after reoxygenation reduced brain weight loss from 27.5+/-4.0% in vehicle pups (n=42) to 12.0+/-3.9% in the treated pups (n=30, P<0.05). Tamoxifen reduces brain injury in the neonatal rat.

The display of sexual behaviors by female rats administered ICI 182,780.

PubMed

Clark, Ann S; Guarraci, Fay A; Megroz, Alison B; Porter, Donna M; Henderson, Leslie P

2003-04-01

ICI 182,780 (ICI) is a pure antiestrogen that when administered systemically does not cross the blood-brain barrier, thus its actions are limited to the periphery. Four experiments were conducted to test the effects of ICI on the display of sexual behaviors in ovariectomized rats. Experiment 1 examined the effects of three doses of ICI (250, 500, and 750 micro g/rat) on sexual receptivity and paced mating behavior in rats primed with estradiol benzoate (EB) in combination with progesterone (P). Experiments 2 and 3 compared the display of sexual behaviors in rats primed with EB+P or EB alone and administered either 250 micro g ICI (Experiment 2) or 500 micro g ICI (Experiment 3). Experiment 4 tested the effects of ICI (250 and 500 micro g) on the expression of estrogen-induced progestin receptors in the uterus. ICI did not affect the display of sexual receptivity in any experiment. In rats primed with EB+P, paced mating behavior was altered by the 500 and 750 micro g, but not the 250 micro g, doses of ICI. The lowest (250 micro g) dose of ICI did alter paced mating behavior in rats primed with EB alone. The effects of ICI on paced mating behavior were manifested by a substantial lengthening of contact-return latencies following intromissions and ejaculations. The percentage of exits were not affected by ICI. Estrogen stimulation of uterine weight and induction of uterine progestin receptors was suppressed by ICI (250 and 500 micro g). ICI effects on paced mating behavior in hormone-primed female rats are likely to reflect antiestrogenic actions in the periphery, including interference with the estrogen induction of progestin receptors.

Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trabace, L., E-mail: trabace@unifg.it; Zotti, M.; Morgese, M.G.

2011-09-01

Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioralmore » tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. - Highlights: > Carvacrol induced a depressive-like phenotype in rats, depending on ovarian cyclicity. > Carvacrol selectively reduced serotonin content in female rats in proestrus phase. > Carvacrol reduced

Excitotoxic lesions of the nucleus paragigantocellularis facilitate male sexual behavior but attenuate female sexual behavior in rats.

PubMed

Normandin, J J; Murphy, A Z

2011-02-23

Little is known regarding the descending inhibitory control of genital reflexes such as ejaculation and vaginal contractions. The brainstem nucleus paragigantocellularis (nPGi) projects bilaterally to the lumbosacral motoneuron pools that innervate the genital musculature of both male and female rats. Electrolytic nPGi lesions facilitate ejaculation in males, leading to the hypothesis that the nPGi is the source of descending inhibition to genital reflexes. However, the function of the nPGi in female sexual behavior remains to be elucidated. To this end, male and female rats received bilateral excitotoxic fiber-sparing lesions of the nPGi, and sexual behavior and sexual behavior-induced Fos expression were examined. In males, nPGi lesions facilitated copulation, supporting the hypothesis that the nPGi, and not fibers-of-passage, is the source of descending inhibition of genital reflexes in male rats. nPGi lesions in males did not alter sexual behavior-induced Fos expression in any brain region examined. nPGi-lesioned females spent significantly less time mating with stimulus males and had significantly longer ejaculation-return latencies compared to baseline. These results did not significantly differ from control females, but this trend warranted further analysis of the reinforcing value of sexual behavior. Both lesioned and non-lesioned females formed a conditioned place preference (CPP) for artificial vaginocervical stimulation (aVCS). However, post-reinforcement, nPGi-lesioned females did not differ in the percentage of time spent in the non-reinforced chamber versus the reinforced chamber, suggesting a weakened CPP for aVCS. nPGi lesions in females reduced sexual behavior-induced Fos expression throughout the hypothalamus and amygdala. Taken together, these results suggest that while nPGi lesions in males facilitate copulation, such lesions in females attenuate several aspects of sexual behavior resulting in a reduction in the rewarding value of copulation

Early handling effect on female rat spatial and non-spatial learning and memory.

PubMed

Plescia, Fulvio; Marino, Rosa A M; Navarra, Michele; Gambino, Giuditta; Brancato, Anna; Sardo, Pierangelo; Cannizzaro, Carla

2014-03-01

This study aims at providing an insight into early handling procedures on learning and memory performance in adult female rats. Early handling procedures were started on post-natal day 2 until 21, and consisted in 15 min, daily separations of the dams from their litters. Assessment of declarative memory was carried out in the novel-object recognition task; spatial learning, reference- and working memory were evaluated in the Morris water maze (MWM). Our results indicate that early handling induced an enhancement in: (1) declarative memory, in the object recognition task, both at 1h and 24h intervals; (2) reference memory in the probe test and working memory and behavioral flexibility in the "single-trial and four-trial place learning paradigm" of the MWM. Short-term separation by increasing maternal care causes a dampening in HPA axis response in the pups. A modulated activation of the stress response may help to protect brain structures, involved in cognitive function. In conclusion, this study shows the long-term effects of a brief maternal separation in enhancing object recognition-, spatial reference- and working memory in female rats, remarking the impact of early environmental experiences and the consequent maternal care on the behavioral adaptive mechanisms in adulthood. Copyright © 2013 Elsevier B.V. All rights reserved.

Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

PubMed

Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

2015-02-01

Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians. © 2014 by The Author(s).

[Pituitary function of dysgenesic femal rats. Studies with grafting method].

PubMed

Vanhems, E; Busquet, J

1975-01-01

Misulban administered to pregnant rats on the 15th day of gestation provoked gonadal dysgenesia in the offspring. Study of the pituitary function of dysgenesic female rats, realized by grafting method, showed gonadotrophic hypersecretion.

Disordered redox metabolism of brain cells in rats exposed to low doses of ionizing radiation or UHF electromagnetic radiation.

PubMed

Burlaka, A P; Druzhyna, M O; Vovk, A V; Lukin, S М

2016-12-01

To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone. The effects of total EMR in the UHF band of non-thermal spectrum were investigated on Wistar rats. The rate of formation of superoxide radicals and the rate of NO synthesis in mitochondria were determined by the EPR. After exposure to ionizing or UHF radiation, the levels of ubisemiquinone in brain tissue of rats decreased by 3 and 1.8 times, respectively. The content of NO-FeS-protein complexes in both groups increased significantly (р < 0.05). In the conditions of ionizing or EMR the rates of superoxide radical generation in electron-transport chain of brain cell mitochondria increased by 1.5- and 2-fold, respectively (р < 0.05). In brain tissue of rats kept in the Chernobyl zone, significant increase of NO content was registered; similar effect was observed in rats treated with UHFR (р < 0.05). The detected changes in the electron transport chain of mitochondria of brain cells upon low-intensity irradiation or UHF EMR cause the metabolic reprogramming of cell mitochondria that increases the rate of superoxide radical generation and nitric oxide, which may initiate the development of neurodegenerative diseases and cancer. This article is part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Rat strain differences in brain structure and neurochemistry in response to binge alcohol.

PubMed

Zahr, Natalie M; Mayer, Dirk; Rohlfing, Torsten; Hsu, Oliver; Vinco, Shara; Orduna, Juan; Luong, Richard; Bell, Richard L; Sullivan, Edith V; Pfefferbaum, Adolf

2014-01-01

Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)). Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment. The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain. As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats. The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.

Regional rat brain noradrenaline turnover in response to restraint stress.

PubMed

Glavin, G B; Tanaka, M; Tsuda, A; Kohno, Y; Hoaki, Y; Nagasaki, N

1983-08-01

Male Wistar rats were starved for 12 hr and then subjected to either 2 hr of wire mesh "envelope" restraint at room temperature; 2 hr of supine restraint in a specially constructed harness at room temperature or were not restrained. Eight brain regions were examined for NA level and the level of its major metabolite, MHPG-SO4. Plasma corticosterone and gastric ulcer incidence were also measured. All restrained rats displayed marked elevations in MHPG-SO4 levels in most brain regions. In addition, several brain regions in restrained animals showed a reduction in NA level. All restrained rats showed elevated plasma corticosterone levels and evidence of gastric lesions. In general, supine restraint produced greater alterations in regional brain NA turnover, greater evidence of ulcer disease, and higher plasma corticosterone levels than did wire mesh restraint. These data suggest that acute but intense stress in the form of restraint causes markedly altered brain NA activity--a possible neurochemical mechanism underlying the phenomenon of stress-induced disease.

Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations.

PubMed

Monte, Aline Santos; Mello, Bruna Stefânia Ferreira; Borella, Vládia Célia Moreira; da Silva Araujo, Tatiane; da Silva, Francisco Eliclécio Rodrigues; Sousa, Francisca Cléa F de; de Oliveira, Antônio Carlos Pinheiro; Gama, Clarissa Severino; Seeman, Mary V; Vasconcelos, Silvânia Maria Mendes; Lucena, David Freitas De; Macêdo, Danielle

2017-07-28

Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

PubMed

Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Testosterone and muscle hypertrophy in female rats

NASA Technical Reports Server (NTRS)

Kuhn, F. E.; Max, S. R.

1985-01-01

The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

NASA Astrophysics Data System (ADS)

Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

1983-10-01

Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

PubMed

Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

2015-06-01

There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. © The Author(s) 2015.

Kin discrimination and female mate choice in the naked mole-rat Heterocephalus glaber.

PubMed

Clarke, F M; Faulkes, C G

1999-10-07

Naked mole-rats are fossorial, eusocial rodents that naturally exhibit high levels of inbreeding. Persistent inbreeding in animals often results in a substantial decline in fitness and, thus, dispersal and avoidance of kin as mates are two common inbreeding avoidance mechanisms. In the naked mole-rat evidence for the former has recently been found. Here we address the latter mechanism by investigating kin recognition and female mate choice using a series of choice tests in which the odour, social and mate preferences of females were determined. Discrimination by females appears to be dependent on their reproductive status. Reproductively active females prefer to associate with unfamiliar males, whereas reproductively inactive females do not discriminate. Females do not discriminate between kin and non-kin suggesting that the criterion for recognition is familiarity, not detection of genetic similarity per se. In the wild, naked mole-rats occupy discrete burrow systems and dispersal and mixing with non-kin is thought to be comparatively rare. Thus, recognition by familiarity may function as a highly efficient kin recognition mechanism in the naked mole-rat. A preference by reproductively active females for unfamiliar males is interpreted as inbreeding avoidance. These findings suggest that, despite an evolutionary history of close inbreeding, naked mole-rats may not be exempt from the effects of inbreeding depression and will attempt to outbreed should the opportunity arise.

Chronic Methamphetamine Effects on Brain Structure and Function in Rats

PubMed Central

Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

2016-01-01

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

PubMed

Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

2016-01-01

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

Increased sensitivity to the acute effects of MDMA ("ecstasy") in female rats.

PubMed

Palenicek, T; Votava, M; Bubenikova, V; Horacek, J

2005-11-15

Behavioral effects of +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are relatively well described in humans as well as in animals. However, little is known about gender differences to the effects of MDMA. The aim of our study was to evaluate gender differences in stimulant effects of MDMA (2.5, 5.0, and 10.0 mg/kg subcutaneously (s.c.)) in male and female Wistar rats. We have used three behavioral methods (activity cage, open field, and elevated plus-maze) each describing a different pattern of spontaneous behavior. In the activity cage, 30 min after the MDMA administration, horizontal and vertical locomotor activities were registered for a period of 3 min. In the open field test rats were placed into an arena 15 min after drug treatment and locomotor activity was registered for a period of 30 min. Finally, in the elevated plus-maze test, rats were given MDMA 30 min prior to measurements and subsequently they were tested in the maze for a period of 5 min. In our experiments we observed a dose-dependent locomotion-enhancing effect of MDMA both in male and female rats in both locomotor tests. Female rats were more sensitive to the locomotor-stimulating effect than males in both tests, suggesting higher sensitivity to the stimulatory effect of MDMA. Further on, MDMA increased thigmotaxis in female rats in the open field test and decreased "anxious-like" behavior in the elevated plus-maze in both genders. In conclusion, we observed higher sensitivity of females to the locomotor-stimulant effect of MDMA. Increased sensitivity of females to the behavioral effects of MDMA can be explained by increased reactivity of serotonergic and dopaminergic systems.

Male and female voices activate distinct regions in the male brain.

PubMed

Sokhi, Dilraj S; Hunter, Michael D; Wilkinson, Iain D; Woodruff, Peter W R

2005-09-01

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

PubMed

Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

2016-01-26

Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

PubMed Central

Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

2016-01-01

Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID:26678032

[Stimulation of D2-receptors improves passive avoidance learning in female rats].

PubMed

Fedotova, Iu O

2012-01-01

The involvement of D2-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. Quinperole (0,1 mg/kg, i.p.), D2-receptor agonist and sulpiride (10,0 mg/kg, i.p.), D2-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic quinperole administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals. Also, quinperole improved spatial learning in proestrous and stimulated it in estrous in Morris water maze. Chronic sulpiride administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D2-receptors in learning/memory processes during ovary cycle in the adult female rats.

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castro, Beatriz; Sánchez, Pilar; Torres, Jesús M., E-mail: torrespi@ugr.es

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. Objectives: We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Methods: Gestating Wistar rats were treated withmore » either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. Results: BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Conclusions: Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. - Highlights: • Juvenile prefrontal cortex of female rats exposed to bisphenol A, F or S was analyzed. • We provide the first in vivo data of BPF and BPS effects in mammal brain. • BPA, BPF and BPS differently affected dopamine and serotonin

The effects of social contact on cocaine intake in female rats.

PubMed

Robinson, Andrea M; Fronk, Gaylen E; Zhang, Huailin; Tonidandel, Scott; Smith, Mark A

2017-08-01

Studies conducted in male rats report that social contact can either facilitate or inhibit drug intake depending on the behavior of social partners. The purpose of the present study was to: (1) examine the effects of social contact on cocaine intake in female rats, (2) examine the behavioral mechanisms by which social contact influences cocaine intake, and (3) examine whether the estrous cycle moderates the effects of social contact on cocaine intake. Female rats were assigned to either isolated or pair-housed conditions in which a social partner either had access to cocaine (cocaine partner) or did not have access to cocaine (abstinent partner). Pair-housed rats were tested in custom-built operant conditioning chambers that allowed both rats to be tested simultaneously in the same chamber. Rats housed with a cocaine partner self-administered more cocaine than isolated rats and rats housed with an abstinent partner. A behavioral economic analysis indicated that these differences were driven by a greater intensity of cocaine demand (i.e., greater intake at lower unit prices) in rats housed with a cocaine partner. Multivariate modeling revealed that the estrous cycle did not moderate the effects of social contact on cocaine intake. These findings indicate that: (1) social contact influences cocaine self-administration in females in a manner similar to that reported in males, (2) these effects are due to differences in the effects of social contact on the intensity of cocaine demand, and (3) these effects are consistent across all phases of the estrous cycle. Copyright © 2017. Published by Elsevier B.V.

Toxicological Effects of Cypermethrin on Female Albino Rats

PubMed Central

Sangha, G. K.; Kaur, Kamalpreet; Khera, K. S.; Singh, Balwinder

2011-01-01

A study was undertaken to evaluate the effects of cypermethrin on reproduction of female albino rats. The experimental rats were fed cypermethrin at 50 mg/kg b. wt. continuously for a period of 2 and 4 weeks. Feed and water intake was also noted daily for control, vehicle treated and cypermethrin-treated rats. It was observed that there was no effect on feed and water intake in treated rats as compared to the control group. Chronic exposure to cypermethrin for 4 weeks resulted in loose fecal pellets and hyperirritability in the treated rats. Treatment related mortality also occurred at the 4th wk of treatment. Significant changes in body weight and various organ weights due to cypermethrin were observed along with disruption of estrous cycle in rats. The body weight gain in treated rats was lower at both 2 and 4 weeks as compared to the control rats. The weight of liver and spleen decreased, while that of kidneys increased as compared to the control rats. Thyroid and adrenal showed increase in weight at both 2 and 4 weeks of treatments. PMID:21430912

Age-Related Memory Impairment Associated With Decreased Endogenous Estradiol in the Hippocampus of Female Rats.

PubMed

Chamniansawat, Siriporn; Sawatdiyaphanon, Chattraporn

It is widely known that not only the gonadal estradiol (E2) but also hippocampal E2 plays an essential role in memory process. However, the role of hippocampal E2-enhanced memory mechanism during aging is largely unknown. The aim of the present study was to investigate the effect of age on E2 concentration, the expression level of its receptors, and key steroidogenic enzymes in hippocampus. We also investigated the effect of microglia activation on E2 synthesis in hippocampal neurons. The results showed that serum E2 was higher in 19-month-old (aged) rats, which exhibited spatial memory decline in the Morris water maze (MWM) test when compared to the younger rats. Hence, serum E2 may not be associated with the reduced spatial memory performance in aging. In contrast, the level of E2 and the expressions of its receptors were significantly decreased in hippocampus of aged female rat compared to younger females. Furthermore, the expressions of key hippocampal steroidogenic enzymes, steroidogenic acute regulatory protein (StAR), and cytochrome P450 (P450) also significantly decreased with age, which resulted in lower hippocampal E2 levels. In addition, we found that the microglia of aged brain highly expressed interleukin 6 (IL-6), which directly inhibited E2 synthesis in hippocampal neurons via suppression of P450 synthesis. Taken together, we summarized that the microglia-derived IL-6 inhibited hippocampal E2 synthesis in aged rats which, in turn, contributed to the deficit of spatial memory performance.

Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

2010-02-01

Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

mTORC1/2 and rapamycin in female Han:SPRD rats with polycystic kidney disease.

PubMed

Belibi, Franck; Ravichandran, Kameswaran; Zafar, Iram; He, Zhibin; Edelstein, Charles L

2011-01-01

Rapamycin slows disease progression in the male Han:SPRD (Cy/+) rat with polycystic kidney disease (PKD). The aim of this study was to determine the effect of rapamycin on PKD and the relative contributions of the proproliferative mammalian target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) in female Cy/+ rats. Female Cy/+ rats were treated with rapamycin from 4 to 12 wk of age. In vehicle-treated Cy/+ rats, kidney volume increased by 40% and cyst volume density (CVD) was 19%. Phosphorylated S6 (p-S6) ribosomal protein, a marker of mTORC1 activity, was increased in Cy/+ rats compared with normal littermate controls (+/+) and decreased by rapamycin. Despite activation of mTORC1 in female Cy/+ rats, rapamycin had no effect on kidney size, CVD, number of PCNA-positive cystic tubular cells, caspase-3 activity, or the number of terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive apoptotic cells. To determine a reason for the lack of effect of rapamycin, we studied the mTORC2 signaling pathway. On immunoblot of kidney, phosphorylated (Ser473) Akt (p-Akt), a marker of mTORC2 activity, was increased in female Cy/+ rats treated with rapamycin. Phosphorylated (Ser657) PKCα, a substrate of mTORC2, was unaffected by rapamycin in females. In contrast, in male rats, where rapamycin significantly decreases PKD, p-Akt (Ser473) was decreased by rapamcyin. PKCα (Ser657) was increased in male Cy/+ rats but was unaffected by rapamycin. In summary, in female Cy/+ rats, rapamycin had no effect on PKD and proproliferative p-Akt (Ser473) activity was increased by rapamycin. There were differential effects of rapamycin on mTORC2 signaling in female vs. male Cy/+ rats.

EPO improved neurologic outcome in rat pups late after traumatic brain injury.

PubMed

Schober, Michelle E; Requena, Daniela F; Rodesch, Christopher K

2018-05-01

In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14 days after injury. Data on long-term effects of erythropoietin on Brain Derived Neurotrophic Factor expression, histology and cognitive function after developmental traumatic brain injury are lacking. We hypothesized that erythropoietin would increase Brain Derived Neurotrophic Factor and improve long-term object recognition in rat pups after controlled cortical impact, associated with increased neuronal fraction in the hippocampus. Rats pups received erythropoietin or vehicle at 1, 24, and 48 h and 7 days after injury or sham surgery followed by histology at 35 days, Novel Object Recognition testing at adulthood, and Brain Derived Neurotrophic Factor measurements early and late after injury. Erythropoietin improved Novel Object Recognition performance and preserved hippocampal volume, but not neuronal fraction, late after injury. Improved object recognition in erythropoietin treated rats was associated with preserved hippocampal volume late after traumatic brain injury. Erythropoietin is approved to treat various pediatric conditions. Coupled with exciting experimental and clinical studies suggesting it is beneficial after neonatal hypoxic ischemic brain injury, our preliminary findings support further study of erythropoietin use after developmental traumatic brain injury. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

PubMed

Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

2017-05-01

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

POST-PUBERTAL DECREASE IN HIPPOCAMPAL DENDRITIC SPINES OF FEMALE RATS

PubMed Central

Yildirim, Murat; Mapp, Oni M.; Janssen, William G.M.; Yin, Weiling; Morrison, John H.; Gore, Andrea C.

2011-01-01

Hippocampal dendritic spine and synapse numbers in female rats vary across the estrous cycle and following experimental manipulation of hormone levels in adulthood. Based on behavioral studies demonstrating that learning patterns are altered following puberty, we hypothesized that dendritic spine number in rat hippocampal CA1 region would change post-pubertally. Female Sprague-Dawley rats were divided into prepubertal (postnatal day (P) 22), peripubertal (P35) and post-pubertal (P49) groups, with the progression of puberty evaluated by vaginal opening, and estrous cyclicity subsequently assessed by daily vaginal smears. Spinophilin immunoreactivity in dendritic spines was used as an index of spinogenesis in area CA1 stratum radiatum (CA1sr) of hippocampus. First, electron microscopy analyses confirmed the presence of spinophilin specifically in dendritic spines of CA1sr, supporting spinophilin as a reliable marker of hippocampal spines in young female rats. Second, stereologic analysis was performed to assess the total number of spinophilin-immunoreactive puncta (i.e. spines) and CA1sr volume in developing rats. Our results indicated that the number of spinophilin-immunoreactive spines in CA1sr was decreased 46% in the post-pubertal group compared to the two younger groups, whereas the volume of the hippocampus underwent an overall increase during this same developmental time frame. Third, to determine a potential role of estradiol in this process, an additional group of rats was ovariectomized (OVX) prepubertally at P22, then treated with estradiol or vehicle at P35, and spinophilin quantified as above in rats perfused on P49. No difference in spinophilin puncta number was found in OVX rats between the two hormone groups, suggesting that this developmental decrease is independent of peripheral estradiol. These changes in spine density coincident with puberty may be related to altered hippocampal plasticity and synaptic consolidation at this phase of maturity. PMID

Probing Intrinsic Resting-State Networks in the Infant Rat Brain

PubMed Central

Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

2016-01-01

Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

PubMed Central

McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

2015-01-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 hours after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in a significantly elevated frontal lobe brain water content 24 and 72 hours after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study’s results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 hours post-SBI. PMID:25975171

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

PubMed

McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

2015-09-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. Copyright © 2015 Elsevier B.V. All rights reserved.

Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development.

PubMed

Carrillo, Beatriz; Collado, Paloma; Díaz, Francisca; Chowen, Julie A; Pérez-Izquierdo, Mª Ángeles; Pinos, Helena

2017-07-11

Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.

Iron overload prevents oxidative damage to rat brain after chlorpromazine administration.

PubMed

Piloni, Natacha E; Caro, Andres A; Puntarulo, Susana

2018-05-15

The hypothesis tested is that Fe administration leads to a response in rat brain modulating the effects of later oxidative challenges such as chlorpromazine (CPZ) administration. Either a single dose (acute Fe overload) or 6 doses every second day (sub-chronic Fe overload) of 500 or 50 mg Fe-dextran/kg, respectively, were injected intraperitoneally (ip) to rats. A single dose of 10 mg CPZ/kg was injected ip 8 h after Fe treatment. DNA integrity was evaluated by quantitative PCR, lipid radical (LR · ) generation rate by electron paramagnetic resonance (EPR), and catalase (CAT) activity by UV spectrophotometry in isolated brains. The maximum increase in total Fe brain was detected after 6 or 2 h in the acute and sub-chronic Fe overload model, respectively. Mitochondrial and nuclear DNA integrity decreased after acute Fe overload at the time of maximal Fe content; the decrease in DNA integrity was lower after sub-chronic than after acute Fe overload. CPZ administration increased LR · generation rate in control rat brain after 1 and 2 h; however, CPZ administration after acute or sub-chronic Fe overload did not affect LR · generation rate. CPZ treatment did not affect CAT activity after 1-4 h neither in control rats nor in acute Fe-overloaded rats. However, CPZ administration to rats treated sub-chronically with Fe showed increased brain CAT activity after 2 or 4 h, as compared to control values. Fe supplementation prevented brain damage in both acute and sub-chronic models of Fe overload by selectively activating antioxidant pathways.

Cognitive differences between male and female rats following exposure to 56Fe particles

NASA Astrophysics Data System (ADS)

Rabin, Bernard; Shukitt-Hale, Barbara; Carrihill-Knoll, Kirsty; Luskin, Katharine; Long, Lauren; Joseph, James

On exploratory class missions astronauts will be exposed to types and doses of radiation (HZE particles) that are not experienced in low earth orbit. While it is likely that the crew will consist of both male and female astronauts, there has been little research on the effects of exposure to HZE particles on cognitive performance in female subjects. While previous research has shown that exposure to HZE particles disrupts cognitive performance in male rats it remains to be established whether or not similar effects will occur with female subjects because estrogen may act as a neuroprotectant. Ovariectomized (OVX) female rats were obtained from Taconic Farms. Thirty mm segments of silastic tubing containing either 180 pg l7-estradiol/mL in sesame oil or vehicle alone were implanted subcutaneously in the neck. Three days following surgery the rats were exposed to 56Fe particles (1000 MeV/n, 0-200 cGy) at the NSRL. Following irradiation the rats were shipped to UMBC for behavioral testing. The results indicated that the pattern of decrements in cognitive performance differed between male and female rats. In addition, for female rats, there were differences in performance as a function of the presence or absence of estradiol. In the vehicle implanted subjects exposure to 56Fe particles did not affect operant responding on an ascending fixed-ratio schedule; whereas irradiation did disrupt responding in OVX animals given estradiol. These results suggest that estrogen may not be protective following exposure to HZE particles. This research was supported by Grant NNX08AM66G from NASA.

Enhancement of in vivo antioxidant ability in the brain of rats fed tannin.

PubMed

Nakajima, Akira; Ueda, Yuto; Matsuda, Emiko; Sameshima, Hiroshi; Ikenoue, Tsuyomu

2013-07-01

The effect of the oral administration of mimosa tannin (MMT) on the rat intra-hippocampal antioxidant ability was examined. Wistar rats at the age of 6 weeks were reared for 8 weeks with the rodent diet (RD) consisting of 0.1 g/kg of MMT (RD-MMT). The antioxidant ability of rat brain was evaluated from the decay of a brain-blood-barrier permeable stable nitroxide, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM) measured by the microdialysis-electron spin resonance system under a freely moving state. The decay rate of PCAM in the brain of rats fed RD-MMT was significantly larger than that of rats fed control rodent diet, which indicates the increase of the antioxidant ability in the brain of rats fed RD-MMT. In vitro study showed that MMT did not reduce PCAM directly but enhanced the reduction of PCAM by ascorbic acid. These results indicate that MMT is a potent antioxidant in vitro and in vivo.

Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative Stress.

PubMed

Özevren, Hüseyin; İrtegün, Sevgi; Deveci, Engin; Aşır, Fırat; Pektanç, Gülsüm; Deveci, Şenay

2017-10-01

Traumatic brain injury causes tissue damage, breakdown of cerebral blood flow and metabolic regulation. This study aims to investigate the protective influence of antioxidant Ganoderma lucidum ( G. lucidum ) polysaccharides (GLPs) on brain injury in brain-traumatized rats. Sprague-Dawley conducted a head-traumatized method on rats by dropping off 300 g weight from 1 m height. Groups were categorized as control, G. lucidum , trauma, trauma+ G. lucidum (20 mL/kg per day via gastric gavage). Brain tissues were dissected from anesthetized rats 7 days after injury. For biochemical analysis, malondialdehyde, glutathione and myeloperoxidase values were measured. In histopathological examination, neuronal damage in brain cortex and changes in blood brain barrier were observed. In the analysis of immunohistochemical and western blot, p38 mitogen-activated protein kinase, vascular endothelial growth factor and cluster of differentiation 68 expression levels were shown. These analyzes demonstrated the beneficial effects of GLPs on brain injury. We propose that GLPs treatment after brain injury could be an alternative treatment to decraseing inflammation and edema, preventing neuronal and glial cells degeneration if given in appropriate dosage and in particular time intervals.

The effect of exercise on carbohydrate preference in female rats.

PubMed

Keeley, R J; Zelinski, E L; Fehr, L; McDonald, R J

2014-02-01

Exercise has a myriad of health benefits, including positive effects against heart disease, diabetes, and dementia. Cognitive performance improves following chronic exercise, both in animal models and humans. Studies have examined the effect of exercise on feeding, demonstrating a preference towards increased food consumption. Further, sex differences exist such that females tend to prefer carbohydrates over other macronutrients following exercise. However, no clear effect of exercise on macronutrient or carbohydrate selection has been described in animal or human studies. This research project sought to determine the effect of voluntary exercise on carbohydrate selection in female rats. Preference for a complex (starch) versus a simple (dextrose) carbohydrate was assessed using a discriminative preference to context paradigm in non-exercising and voluntarily exercising female rats. In addition, fasting blood glucose and performance in the Morris water task was examined in order to verify the effects of exercise on performance in this task. Female rats given access to running wheels preferred a context previously associated with starch, whereas females with no running wheel access preferred a context previously associated with dextrose. No changes in blood glucose were observed. However, cognitive differences in the Morris water task were observed such that voluntary exercise allowed rats to find a new location of a hidden platform following 4 days of training to an old platform location. These results suggest that voluntary exercise may decrease preservative behaviors in a spatial navigation task through the facilitation of plasticity mechanisms. This study is the first of its kind to demonstrate the influence of exercise on taste preference for complex and simple carbohydrates with this context conditioning paradigm. Copyright © 2014 Elsevier Inc. All rights reserved.

Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

PubMed

O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

2000-08-01

Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

PubMed Central

Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

2016-01-01

Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

Dental Fluorosis and Catalase Immunoreactivity of the Brain Tissues in Rats Exposed to High Fluoride Pre- and Postnatally.

PubMed

Güner, Şirin; Uyar-Bozkurt, Süheyla; Haznedaroğlu, Eda; Menteş, Ali

2016-11-01

This study evaluated dental fluorosis of the incisors and immunoreactivity in the brain tissues of rats given chronic fluoride doses pre- and postnatally. Female rats were given drinking water with 0, 30 or 100 ppm fluoride ad libitum throughout gestation and the nursing period. In addition, 63 male offspring were treated with the same water regimens as the mothers after weaning and were followed for 1, 3 or 5 months. The upper and lower incisors were collected, and all teeth were examined under a stereomicroscope and scored by two blinded examiners using a modified rodent enamel fluorosis index. Cortical, hippocampal and cerebellar brain samples were evaluated morphologically and immunohistochemically. All fluoride-treated pups were born with low body weight (p = 0.001). All animals from the fluoride groups had enamel fluorosis with defects of various degrees. The increase in the dental fluorosis scores in the fluoride treatment groups was significant (p < 0.01). The catalase immunoreactivity in the 30- and 100-ppm fluoride groups was significantly higher than that in the controls after 1, 3 and 5 months (p < 0.001). In conclusion, this study showed that rats with dental fluorosis had catalase immunoreactivity in the brain tissues, which may reflect the neurobehavioral toxicity of fluoride.

Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of tigecycline in rat brain tissues.

PubMed

Munyeza, Chiedza F; Shobo, Adeola; Baijnath, Sooraj; Bratkowska, Dominika; Naiker, Suhashni; Bester, Linda A; Singh, Sanil D; Maguire, Glenn E M; Kruger, Hendrik G; Naicker, Tricia; Govender, Thavendran

2016-06-01

Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30 mg/1 mL) cartridges. The samples were separated on a YMC Triart C18 column (150 mm x 3.0 mm. 3.0 µm) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200 ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25 mg/kg TIG intraperitoneally at various time-points. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Shock wave-induced brain injury in rat: novel traumatic brain injury animal model.

PubMed

Nakagawa, Atsuhiro; Fujimura, Miki; Kato, Kaoruko; Okuyama, Hironobu; Hashimoto, Tokitada; Takayama, Kazuyoshi; Tominaga, Teiji

2008-01-01

In blast wave injury and high-energy traumatic brain injury, shock waves (SW) play an important role along with cavitation phenomena. However, due to lack of reliable and reproducible technical approaches, extensive study of this type of injury has not yet been reported. The present study aims to develop reliable SW-induced brain injury model by focusing micro-explosion generated SW in the rat brain. Adult male rats were exposed to single SW focusing created by detonation of microgram order of silver azide crystals with laser irradiation at a focal point of a truncated ellipsoidal cavity of20 mm minor diameter and the major to minor diameter ratio of 1.41 after craniotomy. The pressure profile was recorded using polyvinylidene fluoride needle hydrophone. Animals were divided into three groups according to the given overpressure: Group I: Control, Group II: 12.5 +/- 2.5 MPa (high pressure), and Group III: 1.0 +/- 0.2 MPa (low pressure). Histological changes were evaluated over time by hematoxylin-eosin staining. Group II SW injuries resulted in contusional hemorrhage in reproducible manner. Group III exposure resulted in spindle-shaped changes of neurons and elongation of nucleus without marked neuronal injury. The use of SW loading by micro-explosion is useful to provide a reliable and reproducible SW-induced brain injury model in rats.

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

PubMed

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P < 0.05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P < 0.05). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P < 0.05). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content (r = 0.536, P < 0.01; r = 0.566, P = 0.01). The high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Are the consequences of neonatal hypoxia-ischemia dependent on animals' sex and brain lateralization?

PubMed

Sanches, E F; Arteni, N S; Scherer, E B; Kolling, J; Nicola, F; Willborn, S; Wyse, A T S; Netto, C A

2013-04-24

Hypoxia-ischemia on 3-day-old rats (HIP3) allows the investigation of HI damage in the immature brain. HIP3 is characterized for neurological disabilities caused by white matter injury. This study investigates the relationship between animals' sex and injured hemisphere on HIP3 consequences. Male and female Wistar rats had their right or left common carotid artery occluded under halotane anesthesia and exposed to 8% O2 for 1.5 h. Control rats received sham surgery and exposure to 1.5 h of room air in isolation of their mothers. Sex and injured hemisphere influence in Na+/K+ -ATPase activity 24h after lesion: females and the right brain hemispheres showed decreased enzymatic activity after HIP3. Cognitive impairment was observed in step-down inhibitory avoidance, in which females HIP3 left injured were the most damaged. Histological analysis showed a trend to white matter damage in females left injured without hemispherical nor hippocampal volume decrease in HIP3 rats at postnatal day 21. However, at PND90, hemisphere and sex effects were noted in hemispherical volume and myelination: left brain hemisphere and the females evidenced higher histological damage. Our results points to an increased resistance of male rats and right brain hemisphere to support the impairment caused in Na+/K+ -ATPase activity early after HIP3, and evidencing more discrete behavioral impairments and histological damage at adulthood. Present data adds new evidence of distinct effects of brain lateralization and sex vulnerability on biochemical, behavioral and histological parameters after hypoxia-ischemia. Copyright © 2013 Elsevier B.V. All rights reserved.

Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats.

PubMed

McCreary, J Keiko; Truica, L Sorina; Friesen, Becky; Yao, Youli; Olson, David M; Kovalchuk, Igor; Cross, Albert R; Metz, Gerlinde A S

2016-08-25

Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioral and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal stress than males. Here, we examined if repeated stress across generations may diminish stress resiliency and cumulatively enhance the susceptibility for adverse health outcomes in females. Pregnant female rats of three successive generations were exposed to stress from gestational days 12-18 to generate multigenerational prenatal stress (MPS) in the maternal lineage. Stress response was measured by plasma corticosterone levels and open-field exploration in each generation. Neuromorphological consequences of MPS were investigated in the F3 generation using in vivo manganese-enhanced magnetic resonance imaging (MEMRI), T2-relaxometry, and cytoarchitectonics in relation to candidate gene expression involved in brain plasticity and mental health. Each additional generation of prenatal stress incrementally elevated hypothalamic-pituitary-adrenal axis activation, anxiety-like and aversive behaviors in adult female offspring. Elevated stress responses in the MPS F3 generation were accompanied by reduced neural density in prefrontal cortex, hippocampus and whole brain along with altered brain activation patterns in in vivo MEMRI. MPS increased ephrin receptor A5 (Epha5), neuronal growth regulator (Negr1) and synaptosomal-associated protein 25 (Snap25) gene expression and reduced fibroblast growth factor 12 (Fgf12) in prefrontal cortex. These genes regulate neuronal maturation, arborization and synaptic plasticity and may explain altered brain cytoarchitectonics and connectivity. These findings emphasize that recurrent stress across generations may cumulatively increase stress vulnerability and the risk of adverse health outcomes through perinatal programing in females. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

A study on the antioxidant effect of Coriolus versicolor polysaccharide in rat brain tissues.

PubMed

Chen, Jiayu; Jin, Xiaoyan; Zhang, Liting; Yang, Linjun

2013-01-01

The objective of the study was to investigate the antioxidant effect of Chinese medicine Coriolus versicolor polysaccharide on brain tissue and its mechanism in rats. SOD, MDA and GSH-Px levels in rat brain tissues were determined with SD rats as the animal model. The results showed that Coriolus versicolor polysaccharide can reduce the lipid peroxidation level in brain tissues during exhaustive exercise in rats, and can accelerate the removal of free radicals. The study concluded that its antioxidant effect is relatively apparent.

Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.

PubMed

Hoeksma, Dane; Rebolledo, Rolando A; Hottenrott, Maximilia; Bodar, Yves S; Wiersema-Buist, Janneke J; Van Goor, Harry; Leuvenink, Henri G D

2017-04-01

Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.

Hormonal status and test condition, but not sexual experience, modulate partner preference in female rats.

PubMed

Clark, Ann S; Kelton, Megan C; Guarraci, Fay A; Clyons, Erika Q

2004-05-01

A series of experiments was conducted to determine the contributions of hormonal status, test condition, and sexual experience to the display of partner preference by female rats. Preference for a sexually active male rat over a sexually receptive female rat was assessed in independent groups of female rats tested in a condition limiting physical contact (No Contact) and a condition allowing for sexual interaction (Contact). Although hormonal status and test condition influenced the preference for a sexually active male, repeated testing and sexual experience had no effect. Experiment 1 demonstrated that independent of test condition, preference for the male is stronger in estrogen- and progesterone-primed rats than in rats receiving the vehicle. Moreover, independent of hormone condition, rats tested in the No Contact condition exhibit a stronger preference for the male than rats tested in the Contact condition, reflecting in part the active pacing of mating stimulation by sexually receptive rats tested in the Contact condition. Experiment 2 showed that the overall pattern of partner preference in proestrous and diestrous rats was similar to that observed in ovariectomized, estrogen- and progesterone-primed, and oil-treated rats, respectively. In Experiment 3, rats primed with estrogen alone did not exhibit a preference for the male even though fully receptive. Experiments 4 and 5 demonstrated that sexual experience does not affect the expression of preference for the male in estrogen- and progesterone-primed rats. The present findings demonstrate that the female rat's preference for the male is stable across repeated tests and is not affected by sexual experience. Our results also confirm that gonadal hormones influence the expression of a preference for a sexually active male versus a sexually receptive female and demonstrate that the magnitude of preference is modulated by test conditions.

Regional differences in mu and kappa opioid receptor G-protein activation in brain in male and female prairie voles.

PubMed

Martin, T J; Sexton, T; Kim, S A; Severino, A L; Peters, C M; Young, L J; Childers, S R

2015-12-17

Prairie voles are unusual mammals in that, like humans, they are capable of forming socially monogamous pair bonds, display biparental care, and engage in alloparental behaviors. Both mu and kappa opioid receptors are involved in behaviors that either establish and maintain, or result from pair bond formation in these animals. Mu and kappa opioid receptors both utilize inhibitory G-proteins in signal transduction mechanisms, however the efficacy by which these receptor subtypes stimulate G-protein signaling across the prairie vole neuraxis is not known. Utilizing [(35)S]GTPγS autoradiography, we characterized the efficacy of G-protein stimulation in coronal sections throughout male and female prairie vole brains by [D-Ala2,NMe-Phe4,Gly-ol5]-enkephalin (DAMGO) and U50,488H, selective mu and kappa opioid agonists, respectively. DAMGO stimulation was highest in the forebrain, similar to that found with other rodent species. U-50,488H produced greater stimulation in prairie voles than is typically seen in mice and rats, particularly in select forebrain areas. DAMGO produced higher stimulation in the core versus the shell of the nucleus accumbens (NAc) in females, while the distribution of U-50,488H stimulation was the opposite. There were no gender differences for U50,488H stimulation of G-protein activity across the regions examined, while DAMGO stimulation was greater in sections from females compared to those from males for NAc core, entopeduncular nucleus, and hippocampus. These data suggest that the kappa opioid system may be more sensitive to manipulation in prairie voles compared to mice and rats, and that female prairie voles may be more sensitive to mu agonists in select brain regions than males. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

PubMed Central

2011-01-01

Eleven phosphodiesterase (PDE) families are known, each having several different isoforms and splice variants. Recent evidence indicates that expression of individual PDE family members is tissue-specific. Little is known concerning detailed PDE component expression in brain microvessels where the blood-brain-barrier and the local cerebral blood flow are thought to be regulated by PDEs. The present study attempted to identify PDE family members that are expressed in brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. RNA quality and quantity were determined using an Agilent bioanalyzer. The isolated cortical and infratentorial microvessel total RNA amounts were 2720 ± 750 ng (n = 2) and 250 ± 40 ng (n = 2), respectively. Microarrays with 22 000 transcripts demonstrated that there were 16 PDE transcripts in the PDE superfamily, exhibiting quantifiable density in the microvessels. An additional immunofluorescent study verified that PDE4D (cAMP-specific) and PDE5A (cGMP-specific) were colocalized with RECA-1 (an endothelial marker) in the cerebral cortex using both F344 rats and Sprague–Dawley rats (n = 3–6/strain). In addition, PDE4D and PDE5A were found to be colocalized with alpha-smooth muscle actin which delineates cerebral arteries and arterioles as well as pericytes. In conclusion, a filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed in rat brain microvessels. PMID:22860158

Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

PubMed Central

Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

2014-01-01

Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672

Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

PubMed

Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

2016-01-15

Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Reproductive experience alters prolactin receptor expression in mammary and hepatic tissues in female rats.

PubMed

Bridges, Robert S; Scanlan, Victoria F; Lee, Jong-O; Byrnes, Elizabeth M

2011-08-01

Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer.

Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

PubMed

McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

2016-01-01

No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test.

Female rats express a conditioned object preference for receipt of sexual stimulation.

PubMed

Guterl, Sophie A; McNamara, Tanner A; Klumpp, Gracie C; Meerts, Sarah H

2015-11-01

Female rats alternately approach and avoid the male rat during copulation, potentially reflecting appetitive and aversive aspects of mating, respectively. We developed a novel classical conditioning procedure, conditioned object preference (COP), to test whether female rats show increased approach toward a conditioned stimulus associated directly with receipt of sexual stimulation. During conditioning, one scented object was paired with an appetitive stimulus and a different object plus scent was paired with a control stimulus on a separate day. After conditioning, preference for each object was evaluated with a choice task. Experiment 1 was conducted to verify the procedure. Rats exhibited a significant COP for 1mg/kg amphetamine, indicating that the conditioned object preference procedure is an effective tool for evaluating the rewarding nature of a treatment. In Experiment 2, paced mating to one ejaculation and experimenter-delivered artificial vaginocervical stimulation (aVCS) each induced a COP. The robust COPs for paced mating and aVCS support the notion that female rats experience a reward state during receipt of sexual stimulation. Moreover, the data suggest that any aversive aspects of receipt of sexual stimulation do not overshadow the appetitive effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats

PubMed Central

Allen, Patricia J.; DeBold, Joseph F.; Rios, Maribel; Kanarek, Robin B.

2015-01-01

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine + T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine + EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats.

PubMed

Allen, Patricia J; DeBold, Joseph F; Rios, Maribel; Kanarek, Robin B

2015-03-01

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine+T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine+EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet.

PubMed

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer; Rocic, Petra

2017-04-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. Copyright © 2017 the American Physiological Society.

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet

PubMed Central

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer

2017-01-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. PMID:28087518

Ventilatory drive is enhanced in male and female rats following chronic intermittent hypoxia.

PubMed

Edge, D; Skelly, J R; Bradford, A; O'Halloran, K D

2009-01-01

Obstructive sleep apnoea is characterized by chronic intermittent hypoxia (CIH) due to recurrent apnoea. We have developed a rat model of CIH, which shows evidence of impaired respiratory muscle function. In this study, we wished to characterize the ventilatory effects of CIH in conscious male and female animals. Adult male (n=14) and female (n=8) Wistar rats were used. Animals were placed in chambers daily for 8 h with free access to food and water. The gas supply to one half of the chambers alternated between air and nitrogen every 90 s, for 8 h per day, reducing ambient oxygen concentration in the chambers to 5% at the nadir (intermittent hypoxia; n=7 male, n=4 female). Air supplying the other chambers was switched every 90 s to air from a separate source, at the same flow rates, and animals in these chambers served as controls (n=7 male, n=4 female). Ventilatory measurements were made in conscious animals (typically sleeping) after 10 days using whole-body plethysmography. Normoxic ventilation was increased in both male and female CIH-treated rats compared to controls but this did not achieve statistical significance. However, ventilatory drive was increased in CIH-treated rats of both sexes as evidenced by significant increases in mean and peak inspiratory flow. Ventilatory responses to acute hypoxia (F(I)O(2) = 0.10; 6 min) and hyperoxic hypercapnia (F(I)CO(2) = 0.05; 6 min) were unaffected by CIH treatment in male and female rats (P>0.05, ANOVA). We conclude that CIH increases respiratory drive in adult rats. We speculate that this represents a form of neural plasticity that may compensate for respiratory muscle impairment that occurs in this animal model.

Peripheral anosmia attenuates female-enhanced aggression in male rats.

PubMed

Bergvall, A H; Vega Matuszczyk, J; Dahlöf, L G; Hansen, S

1991-07-01

It is well established that male rats with prior access to sexually active females show enhanced offensive aggression toward unfamiliar male intruders. The present study assessed the importance of the sense of smell for this facilitatory effect. It was found in 2 independent experiments that anosmia, induced peripherally by surgically removing the olfactory epithelium and cutting the olfactory nerves, reduced baseline levels of offensive aggression and significantly attenuated the female-enhanced aggression effect. It was also found that sexual performance of anosmic rats was context-dependent, in that it was more impaired in the homecage environment than in standard observation cages. In contrast to sham-operated males, the experimental animals showed no preference for estrous over anestrous females in a mate choice test. Anosmic males did not appear more fearful than controls, as assessed in a hyponeophagia test, but they showed less exploratory behavior (rearing and head-dipping) in the hole-board test, and less rearing activity in automated activity boxes.

Profiling Coping Strategies in Male and Female Rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

PubMed Central

Kent, Molly; Bardi, Massimo; Hazelgrove, Ashley; Sewell, Kaitlyn; Kirk, Emily; Thompson, Brooke; Trexler, Kristen; Terhune-Cotter, Brennan; Lambert, Kelly

2018-01-01

Coping strategies have been associated with differential stress responsivity, perhaps providing a valuable neurobiological marker for susceptibility to the emergence of depressogenic symptoms or vulnerability to other anxiety-related disorders. Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS). Brains were processed following the DLM training/assessment for fos-activation patterns and several measures of neuroplasticity in relevant areas. Behavioral responses observed during both the CUS and DLM phases of testing suggested that males and females employ different means of gathering information such as increased ambulatory exploration in males and rear responses in females. Fecal samples collected during baseline and following CUS swim exposure revealed higher corticosterone (CORT) in active copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in the basolateral amygdala and a trend toward lower activation in the insula while encountering the prediction error associated with the DLM probe trial. Coping profiles also differentially influenced markers of neuroplasticity; specifically, flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further, less hippocampal glucocorticoid receptor-ir was observed in the flexible copers than the active and passive copers. In sum, flexible coping rats exhibited evidence of emotional resilience as indicated by several neurobiological measures; however, despite increased rates of

Female brain size affects the assessment of male attractiveness during mate choice.

PubMed

Corral-López, Alberto; Bloch, Natasha I; Kotrschal, Alexander; van der Bijl, Wouter; Buechel, Severine D; Mank, Judith E; Kolm, Niclas

2017-03-01

Mate choice decisions are central in sexual selection theory aimed to understand how sexual traits evolve and their role in evolutionary diversification. We test the hypothesis that brain size and cognitive ability are important for accurate assessment of partner quality and that variation in brain size and cognitive ability underlies variation in mate choice. We compared sexual preference in guppy female lines selected for divergence in relative brain size, which we have previously shown to have substantial differences in cognitive ability. In a dichotomous choice test, large-brained and wild-type females showed strong preference for males with color traits that predict attractiveness in this species. In contrast, small-brained females showed no preference for males with these traits. In-depth analysis of optomotor response to color cues and gene expression of key opsins in the eye revealed that the observed differences were not due to differences in visual perception of color, indicating that differences in the ability to process indicators of attractiveness are responsible. We thus provide the first experimental support that individual variation in brain size affects mate choice decisions and conclude that differences in cognitive ability may be an important underlying mechanism behind variation in female mate choice.

Effect of age increase on metabolism and toxicity of ethanol in female rats.

PubMed

Kim, Young C; Kim, Sung Y; Sohn, Young R

2003-12-12

Age-dependent change in the effects of acute ethanol administration on female rat liver was investigated. Female Sprague-Dawley rats, each aged 4, 12, or 50 weeks, received ethanol (2 g/kg) via a catheter inserted into a jugular vein. Ethanol elimination rate (EER), most rapid in the 4 weeks old rats, was decreased as the age advanced. Hepatic alcohol dehydrogenase activity was not altered by age, but microsomal p-nitrophenol hydroxylase activity was significantly greater in the 4 weeks old rats. Relative liver weight decreased with age increase in proportion to reduction of EER. Hepatic triglyceride and malondialdehyde concentrations increased spontaneously in the 50 weeks old nai;ve rats. Ethanol administration (3 g/kg, ip) elevated malondialdehyde and triglyceride contents only in the 4 and the 12 weeks old rats. Hepatic glutathione concentration was increasingly reduced by ethanol with age increase. Ethanol decreased cysteine concentration in the 4 weeks old rats, but elevated it significantly in the older rats. Inhibition of gamma-glutamylcysteine synthetase activity by ethanol was greater with age increase, which appeared to be responsible for the increase in hepatic cysteine. The results indicate that age does not affect the ethanol metabolizing capacity of female rat liver, but the overall ethanol metabolism is decreased in accordance with the reduction of relative liver size. Accordingly induction of acute alcoholic fatty liver is less significant in the old rats. However, progressively greater depletion of glutathione by ethanol in older rats suggests that susceptibility of liver to oxidative damage would be increased as animals grow old.

Nerve growth factor levels and choline acetyltransferase activity in the brain of aged rats with spatial memory impairments.

PubMed

Hellweg, R; Fischer, W; Hock, C; Gage, F H; Björklund, A; Thoenen, H

1990-12-24

Nerve growth factor (NGF) and choline acetyltransferase (ChAT) activity levels were measured in 7 different brain regions in young (3-month-old) and aged (2-years-old) female Sprague-Dawley rats. Prior to analysis the spatial learning ability of the aged rats was assessed in the Morris' water maze test. In the aged rats a significant, 15-30%, increase in NGF levels was observed in 4 regions (septum, cortex, olfactory bulb and cerebellum), whereas the levels in hippocampus, striatum and the brainstem were similar to those of the young rats. The NGF changes did not correlate with the behavioral performance within the aged group. Minor 15-30%, changes in ChAT activity were observed in striatum, brainstem and cerebellum, but these changes did not correlate with the changes in NGF levels in any region. The results indicate that brain NGF levels are maintained at normal or supranormal levels in rats with severe learning and memory impairments. The results, therefore, do not support the view that the marked atrophy and cell loss in the forebrain cholinergic system that is known to occur in the behaviorally impaired aged rats is caused by a reduced availability of NGF in the cholinergic target areas. The results also indicate that the slightly increased levels of NGF are not sufficient to prevent the age-dependent atrophy of cholinergic neurons, although they might be important for the stimulation of compensatory functional changes in a situation where the system is undergoing progressive degeneration.

Effects of Extended Exposure to the Antibacterial Triclosan in the the Adult Female Rat

EPA Science Inventory

Triclosan (TCS), an antibacterial, has been shown to have endocrine disrupting activity in the rat. We reported previously that TCS advanced puberty in the female rat in the female pubertal assay and potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth i...

Osteoprotective Effect of Alfacalcidol in Female Rats with Systemic Chronic Inflammation

USDA-ARS?s Scientific Manuscript database

Studies have shown that alfacalcidol (a hydroxylated form of vitamin D) mitigates glucocorticoid-induced bone loss. This study was undertaken to explore the mechanism and bone microarchitecture of alfacalcidol in rats with systemic chronic inflammation. Thirty female rats (3-month-old) assigned to ...

Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

PubMed

Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

2018-03-01

Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats.

PubMed

Javadi-Paydar, Mehrak; Nguyen, Jacques D; Kerr, Tony M; Grant, Yanabel; Vandewater, Sophia A; Cole, Maury; Taffe, Michael A

2018-06-16

Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation. To compare thermoregulatory and locomotor responses to inhaled ∆ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination using an e-cigarette-based model in male and female rats METHODS: Male and female Wistar rats were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. Animals were then exposed to THC or CBD vapor using a propylene glycol (PG) vehicle. THC dose was adjusted via the concentration in the vehicle (12.5-200 mg/mL) and the CBD (100, 400 mg/mL) dose was also adjusted by varying the inhalation duration (10-40 min). Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation. Plasma samples obtained following inhalation in different groups of rats were compared for THC content. THC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity, and tail-withdrawal responses to THC did not differ between estrus and diestrus. CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. Co-administration of THC with CBD, in a 1:4 ratio, significantly decreased temperature and activity in an approximately additive manner and to similar extent in each sex. Plasma THC varied with the concentration in the PG vehicle but did not differ across rat sex. In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.

Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

PubMed

Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

2016-06-01

Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These

Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.

PubMed

Gaspar, Renato Simões; Benevides, Renata Ohana Alves; Fontelles, João Lucas de Lima; Vale, Caroline Castro; França, Lucas Martins; Barros, Paulo de Tarso Silva; Paes, Antonio Marcus de Andrade

2016-05-01

Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis. © 2016 Society for Endocrinology.

Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female rats.

PubMed

Peysepar, Elham; Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

2016-01-01

Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. Sixty Wistar male and female rats were used in eight experimental groups. Both genders received GABA (50 μg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.) was added from day 8 to the end of the study, and they were compared with the control groups. At the end of the study, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage was also determined via staining. CP significantly increased the serum levels of Cr and BUN, kidney weight, and kidney tissue damage score in both genders (P<0.05). GABA did not attenuate these markers in males; even these biomarkers were intensified in females. Serum level of Mg, and testis and uterus weights did not alter in the groups. However, the groups were significantly different in terms of nitrite and MDA levels. It seems that GABA did not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal damage in female rats.

Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats.

PubMed

Lalanza, Jaume F; Sanchez-Roige, Sandra; Cigarroa, Igor; Gagliano, Humberto; Fuentes, Silvia; Armario, Antonio; Capdevila, Lluís; Escorihuela, Rosa M

2015-11-05

Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non-handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders.

Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats

PubMed Central

Lalanza, Jaume F.; Sanchez-Roige, Sandra; Cigarroa, Igor; Gagliano, Humberto; Fuentes, Silvia; Armario, Antonio; Capdevila, Lluís; Escorihuela, Rosa M.

2015-01-01

Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non-handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders. PMID:26538081

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

PubMed

Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

2018-01-01

HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats

PubMed Central

Sinclair, Elaine B.; Culbert, Kristen M.; Gradl, Dana R.; Richardson, Kimberlei A.; Klump, Kelly L.; Sisk, Cheryl L.

2017-01-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague–Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1 h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial pre-frontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal

Memantine ameliorates autistic behavior, biochemistry & blood brain barrier impairments in rats.

PubMed

Kumar, Hariom; Sharma, Bhupesh

2016-06-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, commonly characterized by altered social behavior, communication, biochemistry and pathological conditions. One percent of the worldwide population suffers from autism and males suffer more than females. NMDA receptors have the important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. This study has been designed to investigate the role of memantine, a NMDA receptor modulator, in prenatal valproic acid-induced autism in rats. Animals with prenatal valproic acid have shown the reduction in social interaction (three-chamber social behavior apparatus), spontaneous alternation (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, prenatal valproic acid-treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood-brain barrier permeability. Treatment with memantine has significantly attenuated prenatal valproic acid-induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, memantine has also attenuated the prenatal valproic acid-induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood-brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behavior, biochemistry and blood-brain barrier impairment in animals, which were significantly attenuated by memantine. NMDA receptor modulators like memantine should be explored further for the therapeutic

Developmental changes in the hypothalamic mRNA expression levels of brain-derived neurotrophic factor and serum leptin levels: Their responses to fasting in male and female rats.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Munkhzaya, Munkhsaikhan; Tungalagsuvd, Altankhuu; Yiliyasi, Maira; Kuwahara, Akira; Irahara, Minoru

2016-11-01

The actions and responses of hypothalamic appetite regulatory factors change markedly during the neonatal to pre-pubertal period in order to maintain appropriate metabolic and nutritional conditions. In this study, we examined the developmental changes in the hypothalamic mRNA levels of brain-derived neurotrophic factor (BDNF), which is a potent anorectic factor and the changes in the sensitivity of the hypothalamic expression of this factor to fasting during the neonatal to pre-pubertal period. Under fed conditions, hypothalamic BDNF mRNA expression decreased during development in both male and female rats. Similarly, the serum levels of leptin, which is a positive regulator of hypothalamic BDNF expression, also tended to fall during the developmental period. The serum leptin level and the hypothalamic BDNF mRNA level were found to be positively correlated in both sexes under the fed conditions. Hypothalamic BDNF mRNA expression was decreased by 24h fasting (separating the rats from their mothers) in the early neonatal period (postnatal day 10) in both males and females, but no such changes were seen at postnatal day 20. Twenty-four hours' fasting (food deprivation) did not affect hypothalamic BDNF mRNA expression in the pre-pubertal period (postnatal day 30). On the other hand, the rats' serum leptin levels were decreased by 24h fasting (separating the rats from their mothers at postnatal day 10 and 20, and food deprivation at postnatal day 30) throughout the early neonatal to pre-pubertal period. The correlation between serum leptin and hypothalamic BDNF mRNA levels was not significant under the fasted conditions. It can be speculated that leptin partially regulates hypothalamic BDNF mRNA levels, but only in fed conditions. Such changes in hypothalamic BDNF expression might play a role in maintaining appropriate metabolic and nutritional conditions and promoting normal physical development. In addition, because maternal separation induces a negative energy

24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression.

PubMed

Haleem, D J; Yasmeen, A; Haleem, M A; Zafar, A

1995-01-01

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with saline daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day saline injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with saline on the 6th day. Plasma total and free tryptophan were not altered in these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day saline injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.

Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.

PubMed

Golcu, Doruk; Gebre, Rahiwa Z; Sapolsky, Robert M

2014-08-01

The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner

PubMed Central

Golcu, Doruk; Gebre, Rahiwa Z.; Sapolsky, Robert M.

2016-01-01

The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. PMID:24907696

Activity-based anorexia is associated with reduced hippocampal cell proliferation in adolescent female rats.

PubMed

Barbarich-Marsteller, Nicole C; Fornal, Casimir A; Takase, Luiz F; Bocarsly, Miriam E; Arner, Candice; Walsh, B Timothy; Hoebel, Bartley G; Jacobs, Barry L

2013-01-01

Activity-based anorexia (ABA) is an animal model of anorexia nervosa that mimics core features of the clinical psychiatric disorder, including severe food restriction, weight loss, and hyperactivity. The ABA model is currently being used to study starvation-induced changes in the brain. Here, we examined hippocampal cell proliferation in animals with ABA (or the appropriate control conditions). Adolescent female Sprague-Dawley rats were assigned to 4 groups: control (24h/day food access), food-restricted (1h/day food access), exercise (24h/day food and wheel access), and ABA (1h/day food access, 24h/day wheel access). After 3 days of ABA, 5-bromo-2'-deoxyuridine (BrdU; 200mg/kg, i.p.) was injected and the rats were perfused 2h later. Brains were removed and subsequently processed for BrdU and Ki67 immunohistochemistry. The acute induction of ABA reduced cell proliferation in the dentate gyrus. This effect was significant in the hilus region of the dentate gyrus, but not in the subgranular zone, where adult neurogenesis occurs. Marked decreases in cell proliferation were also observed in the surrounding dorsal hippocampus and in the corpus callosum. These results indicate a primary effect on gliogenesis rather than neurogenesis following 3 days of ABA. For each brain region studied (except SGZ), there was a strong positive correlation between the level of cell proliferation and body weight/food intake. Future studies should examine whether these changes are maintained following long-term weight restoration and whether alterations in neurogenesis occur following longer exposures to ABA. Copyright © 2012 Elsevier B.V. All rights reserved.

Impact of three endocrine disruptors, Bisphenol A, Genistein and Vinclozolin on female rat enamel.

PubMed

Jedeon, K; Berdal, A; Babajko, A

2016-06-28

Concerns about the potential adverse effectsof endocrine disruptors (EDs) have been increasingover the last three decades. BisphenolA (BPA), genistein (G) and vinclozolin (V) arethree widely used EDs sharing similar effects.Since populations are exposed to many diverseEDs simultaneously, we demonstratedrecently their impact alone or combined onmale rat tooth enamel. The purpose of thisstudy was therefore to assess their effects onfemale rat tooth enamel in order to understandwhy they are differentially sensitive. Ratswere exposed daily in utero and after birth tolow doses of EDs during the critical fetal andsuckling periods when amelogenesis takesplace. Enamel of rats exposed to EDs presentedopaque areas of hypomineralization. Theproportion of affected rats was the highestin the groups of rats treated with BPA aloneand higher in males than in females (in all thegroups). Comparison of enamel key gene expressionlevels showed modulations of Klk4and Enamelin in males but no significant variationsin females. These findings show thatfemale rats are less affected than males bythe three EDs chosen in this study and suggestthat enamel hypomineralization may differbetween males and females.

Dietary selenium requirements based on tissue selenium concentration and glutathione peroxidase activities in old female rats.

PubMed

Sunde, Roger A; Thompson, Kevin M

2009-01-01

Dietary nutrient requirements for older animals have been studied far less than have requirements for young growing animals. To determine dietary selenium (Se) requirements in old rats, we fed female weanling rats a Se-deficient diet (0.007 microg Se/g) or supplemented rats with graded levels of dietary Se (0-0.3 microg Se/g) as Na(2)SeO(3) for 52 weeks. At no point did Se deficiency or level of Se supplementation have a significant effect (P>0.05) on growth. To determine Se requirements, Se response curves were determined for 7 Se-dependent parameters. We found that minimum dietary Se requirements in year-old female rats were at or below 0.05 microg Se/g diet based on liver Se, red blood cell glutathione peroxidase (Gpx1) activity, plasma Gpx3 activity, liver and kidney Gpx1 activity, and liver and kidney Gpx4 activity. In conclusion, this study found that dietary Se requirements in old female rats were decreased at least 50% relative to requirements found in young, rapidly growing female rats. Collectively, this indicates that the homeostatic mechanisms related to retention and maintenance of Se status are still fully functional in old female rats.

EFFECT OF CONAZOLE FUNGICIDES ON REPRODUCTIVE DEVELOPMENT IN THE FEMALE RAT

EPA Science Inventory

Three triazole fungicides were evaluated for effects on female rat reproductive development. Rats were exposed via feed to propiconazole (P) (100, 500, or 2500 ppm), myclobutanil (M) (100, 500, or 2000 ppm), or triadimefon (T) (100, 500, or 1800 ppm) from gestation day 6 to postn...

The Effects of Stereotactic Cerebroventricular Administration of Albumin, Mannitol, Hypertonic Sodium Chloride, Glycerin and Dextran in Rats with Experimental Brain Edema.

PubMed

Ates, Tuncay; Gezercan, Yurdal; Menekse, Guner; Turkoz, Yusuf; Parlakpinar, Hakan; Okten, Ali Ihsan; Akyuva, Yener; Onal, Selami Cagatay

2017-01-01

To evaluate the effects of cerebroventricular administration of hyperoncotic/hyperosmotic agents on edematous brain tissue in rats with experimental head trauma. The study included 54 female Sprague-Dawley rats with weights ranging between 200 and 250 g. Six experimental groups were examined with each group containing 9 rats. All rats were exposed to head trauma, and treatment groups were administered 2 µl of one of the drugs (albumin, mannitol, hypertonic sodium chloride (NaCl), glycerin and dextran) 6, 12 and 24 hours after the trauma via the cerebroventricular route and using a stereotactic device. Rats were sacrificed 48 hours after the trauma, and brain tissues were extracted without damage. Biochemical analyses including reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were performed on the injured left hemisphere. Compared with the control group, the albumin, mannitol, 3% NaCl and glycerin treatment groups revealed dramatic increases in GSH levels (p < 0.001). Levels of MDA, which is the end-product of brain edema and lipid peroxidation, failed to show a statistically significant decrease, but there was a decreasing trend observed in the inter-group comparisons. NO levels were also decreased in the 3% NaCl treatment group. An analysis of TNF-α and IL-1β, two proinflammatory cytokines associated with the trauma, revealed that IL-1β decreased significantly in all treatment groups (p=0.001), whereas no significant difference was detected in TNF-α levels. Cerebroventricular administration of hyperoncotic/hyperosmotic agents provides substantial effects on the treatment of brain edema.

Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2011-03-01

Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

Development of brain-wide connectivity architecture in awake rats.

PubMed

Ma, Zilu; Ma, Yuncong; Zhang, Nanyin

2018-08-01

Childhood and adolescence are both critical developmental periods, evidenced by complex neurophysiological changes the brain undergoes and high occurrence rates of neuropsychiatric disorders during these periods. Despite substantial progress in elucidating the developmental trajectories of individual neural circuits, our knowledge of developmental changes of whole-brain connectivity architecture in animals is sparse. To fill this gap, here we longitudinally acquired rsfMRI data in awake rats during five developmental stages from juvenile to adulthood. We found that the maturation timelines of brain circuits were heterogeneous and system specific. Functional connectivity (FC) tended to decrease in subcortical circuits, but increase in cortical circuits during development. In addition, the developing brain exhibited hemispheric functional specialization, evidenced by reduced inter-hemispheric FC between homotopic regions, and lower similarity of region-to-region FC patterns between the two hemispheres. Finally, we showed that whole-brain network development was characterized by reduced clustering (i.e. local communication) but increased integration (distant communication). Taken together, the present study has systematically characterized the development of brain-wide connectivity architecture from juvenile to adulthood in awake rats. It also serves as a critical reference point for understanding circuit- and network-level changes in animal models of brain development-related disorders. Furthermore, FC data during brain development in awake rodents contain high translational value and can shed light onto comparative neuroanatomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats.

PubMed

Martino-Andrade, Anderson J; Morais, Rosana N; Spercoski, Katherinne M; Rossi, Stefani C; Vechi, Marina F; Golin, Munisa; Lombardi, Natália F; Greca, Cláudio S; Dalsenter, Paulo R

2010-01-08

Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.

PubMed

Glendenning, Michele L; Lovekamp-Swan, Tara; Schreihofer, Derek A

2008-11-14

Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups. Two weeks later, halothane-anesthetized rats underwent middle cerebral artery (MCA) occlusion by interparenchymal stereotactic injection of the potent vasoconstrictor endothelin 1 (180pmoles/2microl) near the middle cerebral artery. Laser-Doppler flowmetry (LDF) revealed similar reductions in cerebral blood flow in both groups. Animals were behaviorally evaluated before, and 2 days after, stroke induction, and infarct size was evaluated. In agreement with other models, estrogen treatment significantly reduced infarct size evaluated by both TTC and Fluoro-Jade staining and behavioral deficits associated with stroke. Stroke size was significantly correlated with LDF in both groups, suggesting that cranial perfusion measures can enhance success in this model.

Incorporation of new neurons in the olfactory bulb after paced mating in the female rat.

PubMed

Alvarado-Martínez, R; Paredes, R G

2018-05-02

One of the regions that constantly produces neurogenesis in the adult brain is the subventricular zone (SVZ), whose new cells migrate to the olfactory bulbs (OB). When the females regulate the copulatory events (paced mating) the number of new cells in the SVZ increases, as well as those observed in the OB 15 days later. However, no changes were observed in the number of cells 45 days after the females paced the sexual interaction. Constant sensory stimulation is an important promoter of cell survival in the OB circuit. Hence, we increased the number of mating sessions in this study to cover the period where stimulation of the new cells is critical for their incorporation into pre-existing circuits in the OB. Ovariectomized female Wistar rats, were injected with the mitotic marker 5-bromo-2'-deoxyuridine (BrdU, 100 mg/kg, per injection) before, at the end and one hour after mating. Sexual behavior was recorded for 1 h in 10 weekly sessions. After the last mating session, brain sections were processed to determine BrdU immunoreactivity. Our results indicate that females that paced the sexual interaction for 10 sessions had a higher number of cells in the glomerular layer (GL) of the accessory olfactory bulb (AOB) and a higher number of neurons in the granular layer (GrL) of the main olfactory bulb (MOB) in comparison to the control group. These results indicate that continued sexual interaction contributes to the integration of new cells and neurons, induced in the first sexual experience, into pre-exiting circuits of the OB. Copyright © 2018 Elsevier B.V. All rights reserved.

Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems

PubMed Central

Lukkes, Jodi L.; Engelman, Glenn H.; Zelin, Naomi S.; Hale, Matthew W.; Lowry, Christopher A.

2012-01-01

Our previous studies have shown that post-weaning social isolation of male rats leads to sensitization of serotonergic systems and increases in anxiety-like behavior in adulthood. Although studies in humans suggest that females have an increased sensitivity to stress and risk for the development of neuropsychiatric illnesses, most studies involving laboratory rats have focused on males while females have been insufficiently studied. The objective of this study was to investigate the effects of post-weaning social isolation on subsequent responses of an anxiety-related dorsal raphe nucleus (DR)-basolateral amygdala system to pharmacological challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142; a partial inverse agonist at the benzodiazepine allosteric site on the γ-aminobutyric acid (GABA)A receptor). Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-reared for an additional 2 weeks. We then used dual immunohistochemical staining for c-Fos and tryptophan hydroxylase in the DR or single immunohistochemical staining for c-Fos in the basolateral amygdala. Isolation-reared rats, but not group-reared rats, injected with FG-7142 had increased c-Fos expression within the basolateral amygdala and in serotonergic neurons in the dorsal, ventrolateral, caudal and interfascicular parts of the DR relative to appropriate vehicle-injected control groups. These data suggest that post-weaning social isolation of female rats sensitizes a DR-basolateral amygdala system to stress-related stimuli, which may lead to an increased sensitivity to stress- and anxiety-related responses in adulthood. PMID:22297173

Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

PubMed Central

Ruderman, Neil B.; Ross, Peter S.; Berger, Michael; Goodman, Michael N.

1974-01-01

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the

Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior

PubMed Central

Cheng, Ruey-Kuang; MacDonald, Christopher J.; Williams, Christina L.; Meck, Warren H.

2008-01-01

Choline availability in the maternal diet has a lasting effect on brain and behavior of the offspring. To further delineate the impact of early nutritional status, we examined effects of prenatal-choline supplementation on timing, emotion, and memory performance of adult male and female rats. Rats that were given sufficient choline (CON: 1.1 g/kg) or supplemental choline (SUP: 5.0 g/kg) during embryonic days (ED) 12–17 were trained with a differential reinforcement of low-rate (DRL) schedule that was gradually transitioned through 5-, 10-, 18-, 36-, and 72-sec criterion times. We observed that SUP-females emitted more reinforced responses than CON-females, which were more efficient than both groups of males. In addition, SUP-males and SUP-females exhibited a reduction in burst responding (response latencies <2 sec) compared with both groups of CON rats. Furthermore, despite a reduced level of burst responding, the SUP-males made more nonreinforced responses prior to the DRL criterion as a result of maintaining the previous DRL criterion following transition to a new criterion. In summary, long-lasting effects of prenatal-choline supplementation were exhibited by reduced frustrative DRL responding in conjunction with the persistence of temporal memory in SUP-males and enhanced temporal exploration and response efficiency in SUP-females. PMID:18323570

Pregnancy or stress decrease complexity of CA3 pyramidal neurons in the hippocampus of adult female rats.

PubMed

Pawluski, J L; Valença, A; Santos, A I M; Costa-Nunes, J P; Steinbusch, H W M; Strekalova, T

2012-12-27

Pregnancy is a time of distinct neural, physiological and behavioral plasticity in the female. It is also a time when a growing number of women are vulnerable to stress and experience stress-related diseases, such as depression and anxiety. However, the impact of stress during gestation on the neurobiology of the mother has yet to be determined, particularly with regard to changes in the hippocampus; a brain area that plays an important role in stress-related diseases. Therefore, the aim of the present study was to understand how stress and reproductive state may alter dendritic morphology of CA1 and CA3 pyramidal neurons in the hippocampus. To do this, adult age-matched pregnant and virgin female Wistar rats were divided into two conditions: (1) control and (2) stress. Females in the stress condition were restrained for 1h/day for the last 2 weeks of gestation and at matched time-points in virgin females. Females were sacrificed the day after the last restraint session and brains were processed for Golgi impregnation. Dendritic length and number of branch points were quantified for apical and basal regions of CA1 and CA3 pyramidal neurons. Results show that regardless of reproductive state, stressed females had significantly shorter apical dendrites and fewer apical branch points in CA3 pyramidal cells. In addition, pregnant females, regardless of stress exposure, had less complex CA3 pyramidal neurons, as measured by Sholl analysis. No differences between conditions were seen in morphology of CA1 pyramidal neurons. This work shows that both repeated restraint stress and pregnancy affect dendritic morphology by decreasing complexity of CA3, but not CA1, neurons in the hippocampus. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

PubMed

Guevara-Guzmán, R; Arriaga, V; Kendrick, K M; Bernal, C; Vega, X; Mercado-Gómez, O F; Rivas-Arancibia, S

2009-03-31

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats

PubMed Central

Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Taché, Yvette

2011-01-01

Abdominal surgery-induced postoperative gastric ileus is well established to induce Fos expression in specific brain nuclei in rats within 2-h after surgery. However, the phenotype of activated neurons has not been thoroughly characterized. Nesfatin-1 was recently discovered in the rat hypothalamus as a new anorexigenic peptide that also inhibits gastric emptying and is widely distributed in rat brain autonomic nuclei suggesting an involvement in stress responses. Therefore, we investigated whether abdominal surgery activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Two hours after abdominal surgery with cecal palpation under short isoflurane anesthesia or anesthesia alone, rats were transcardially perfused and brains processed for double immunohistochemical labeling of Fos and nesfatin-1. Abdominal surgery, compared to anesthesia alone, induced Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), Edinger-Westphal nucleus (EW), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling showed that of the activated cells, 99% were nesfatin-1-immunoreactive in the SON, 91% in the LC, 82% in the rRPa, 74% in the EW and VLM, 71% in the anterior parvicellular PVN, 47% in the lateral magnocellular PVN, 41% in the medial magnocellular PVN, 14 % in the NTS and 9% in the medial parvicellular PVN. These data established nesfatin-1 immunoreactive neurons in specific hypothalamic and pontine nuclei as part of the neuronal response to abdominal surgery and suggest a possible implication of nesfatin-1 in the alterations of food intake and gastric transit associated with such a stressor. PMID:19944727

Reproductive Experience Alters Prolactin Receptor Expression in Mammary and Hepatic Tissues in Female Rats1

PubMed Central

Bridges, Robert S.; Scanlan, Victoria F.; Lee, Jong-O; Byrnes, Elizabeth M.

2011-01-01

Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer. PMID:21508351

Why are maternally separated females inflexible? Brain activity pattern of COx and c-Fos.

PubMed

Banqueri, María; Méndez, Marta; Arias, Jorge L

2018-06-15

Subjects' early life events will affect them later in life. When these events are stressful, such as child abuse in humans or repeated maternal separation in rodents, subjects can show some behavioral and brain alterations. This study used young adult female Wistar rats that were maternally raised (AFR), maternally separated from post-natal day (PND) 1 to PND10 (MS10), or maternally separated from PND1 to PND21 (MS21), in order to assess the effects of maternal separation (MS) on spatial learning and memory, as well as cognitive flexibility, using the Morris Water Maze (MWM). We performed quantitative cytochrome oxidase (COx) histochemistry on selected brain areas in order to identify whether maternal separation affects brain energy metabolism. We also performed c-Fos immunohistochemistry on the medial prefrontal cortex (mPFC), thalamus, and hippocampus to explore whether this immediate early gene activity was altered in stressed subjects. We obtained a similar spatial learning pattern in maternally raised and maternally separated subjects on the reference memory task, but only the controls were flexible enough to solve the reversal learning successfully. Separated groups showed less c-Fos activity in the mPFC and less complex neural networks on COx. Copyright © 2018 Elsevier Inc. All rights reserved.

Strain-related differences after experimental traumatic brain injury in rats.

PubMed

Reid, Wendy Murdock; Rolfe, Andrew; Register, David; Levasseur, Joseph E; Churn, Severn B; Sun, Dong

2010-07-01

The present study directly compares the effects of experimental brain injury in two commonly used rat strains: Fisher 344 and Sprague-Dawley. We previously found that Fisher rats have a higher mortality rate and more frequent seizure attacks at the same injury level than Sprague-Dawley rats. Although strain differences in rats are commonly accepted as contributing to variability among studies, there is a paucity of literature addressing strain influence in experimental neurotrauma. Therefore this study compares outcome measures in two rat strains following lateral fluid percussion injury. Fisher 344 and Sprague-Dawley rats were monitored for changes in physiological measurements, intracranial pressure, and electroencephalographic activity. We further analyzed neuronal degeneration and cell death in the injured brain using Fluoro-Jade-B (FJB) histochemistry and caspase-3 immunostaining. Behavioral studies using the beam walk and Morris water maze were conducted to characterize strain differences in both motor and cognitive functional recovery following injury. We found that Fisher rats had significantly higher intracranial pressure, prolonged seizure activity, increased FJB-positive staining in the injured cortex and thalamus, and increased caspase-3 expression than Sprague-Dawley rats. On average, Fisher rats displayed a greater amount of total recording time in seizure activity and had longer ictal durations. The Fisher rats also had increased motor deficits, correlating with the above results. In spite of these results, Fisher rats performed better on cognitive tests following injury. The results demonstrate that different rat strains respond to injury differently, and thus in preclinical neurotrauma studies strain influence is an important consideration when evaluating outcomes.

Strain-Related Differences after Experimental Traumatic Brain Injury in Rats

PubMed Central

Rolfe, Andrew; Register, David; Levasseur, Joseph E.; Churn, Severn B.; Sun, Dong

2010-01-01

Abstract The present study directly compares the effects of experimental brain injury in two commonly used rat strains: Fisher 344 and Sprague-Dawley. We previously found that Fisher rats have a higher mortality rate and more frequent seizure attacks at the same injury level than Sprague-Dawley rats. Although strain differences in rats are commonly accepted as contributing to variability among studies, there is a paucity of literature addressing strain influence in experimental neurotrauma. Therefore this study compares outcome measures in two rat strains following lateral fluid percussion injury. Fisher 344 and Sprague-Dawley rats were monitored for changes in physiological measurements, intracranial pressure, and electroencephalographic activity. We further analyzed neuronal degeneration and cell death in the injured brain using Fluoro-Jade-B (FJB) histochemistry and caspase-3 immunostaining. Behavioral studies using the beam walk and Morris water maze were conducted to characterize strain differences in both motor and cognitive functional recovery following injury. We found that Fisher rats had significantly higher intracranial pressure, prolonged seizure activity, increased FJB-positive staining in the injured cortex and thalamus, and increased caspase-3 expression than Sprague-Dawley rats. On average, Fisher rats displayed a greater amount of total recording time in seizure activity and had longer ictal durations. The Fisher rats also had increased motor deficits, correlating with the above results. In spite of these results, Fisher rats performed better on cognitive tests following injury. The results demonstrate that different rat strains respond to injury differently, and thus in preclinical neurotrauma studies strain influence is an important consideration when evaluating outcomes. PMID:20392137

Boron deprivation alters rat behaviour and brain mineral composition differently when fish oil instead of safflower oil is the diet fat source.

PubMed

Nielsen, Forrest H; Penland, James G

2006-01-01

To determine whether boron deprivation affects rat behaviour and whether behavioural responses to boron deprivation are modified by differing amounts of dietary long-chain omega-3 fatty acids. Female rats were fed diets containing 0.1 mg (9 micromol)/kg boron in a factorial arrangement with dietary variables of supplemental boron at 0 and 3mg (278 micromol)/kg and fat sources of 75 g/kg safflower oil or 65 g/kg fish (menhaden) oil plus 10 g/kg linoleic acid. After 6 weeks, six females per treatment were bred. Dams and pups continued on their respective diets through gestation, lactation and after weaning. Between ages 6 and 20 weeks, behavioural tests were performed on 13-15 male offspring from three dams in each dietary treatment. The rats were euthanized at age 21 weeks for the collection of tissues and blood. At ages 6 and 19 weeks, auditory startle was evaluated with an acoustic startle system and avoidance behaviour was evaluated by using an elevated plus maze. At ages 7 and 20 weeks, spontaneous behaviour activity was evaluated with a photobeam activity system. A brightness discrimination test was performed on the rats between age 15 and 16 weeks. Brain mineral composition was determined by coupled argon plasma atomic emission spectroscopy. Plasma total glutathione was determined by HPLC and total cholesterol and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) were determined by using commercially available kits. Boron-deficient rats were less active than boron-adequate rats when fed safflower oil based on reduced number, distance and time of horizontal movements, front entries, margin distance and vertical breaks and jumps in the spontaneous activity evaluation. Feeding fish oil instead of safflower oil attenuated the activity response to boron deprivation. In the plus maze evaluation, the behavioural reactivity of the boron-deficient rats fed fish oil was noticeably different than the other three treatments. They made more entries into both open and closed

Influences of chemical sympathectomy and simulated weightlessness on male and female rats

NASA Technical Reports Server (NTRS)

Woodman, Christopher R.; Stump, Craig S.; Stump, Jane A.; Sebastian, Lisa A.; Rahman, Z.; Tipton, Charles M.

1991-01-01

Consideration is given to a study aimed at determining whether the sympathetic nervous system is associated with the changes in maximum oxygen consumption (VO2max), run time, and mechanical efficiency observed during simulated weightlessness in male and female rats. Female and male rats were compared for food consumption, body mass, and body composition in conditions of simulated weightlessness to provide an insight into how these parameters may influence aerobic capacity and exercise performance. It is concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. It is noted that the mechanisms remain unclear at this time.

Low- and high-intensity treadmill exercise attenuates chronic morphine-induced anxiogenesis and memory impairment but not reductions in hippocampal BDNF in female rats.

PubMed

Ghodrati-Jaldbakhan, Shahrbanoo; Ahmadalipour, Ali; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Alizadeh, Maryam

2017-05-15

Previous studies from our laboratory have shown that treadmill exercise alleviates the deficits in cognitive functions and anxiety behaviors induced by chronic exposure to morphine in male rats. In this study, we investigated the effects of low and high intensities of treadmill exercise on spatial memory, anxiety-like behaviors, and biochemical changes in the hippocampus and serum of morphine-treated female rats. The adult virgin female rats were injected with bi-daily doses (10mg/kg, at 12h intervals) of morphine over a period of 10days. Following these injections, the rats were exercised under low or high intensities for 30min per session on five days a week for four weeks. After exercise training, object location memory, anxiety profile, hippocampal BDNF, and serum corticosterone and BDNF were examined. Morphine-treated animals exhibited increased anxiety levels, impaired object location memory, and reduced hippocampal BDNF. Exercise alleviated these impairing effects on anxiety profile and memory but not hippocampal BDNF. The high-intensity exercise even further reduced the hippocampal BDNF. Additionally, both exercise regimens in the morphine group and the high exercise in the saline group reduced serum BDNF. Finally, the high-intensity exercise enhanced corticosterone serum. These findings indicate that the negative cognitive and behavioral effects of chronic exposure to morphine could be relieved by forced exercise in female rats. However, the exercise intensity is an important factor to be considered during exercise training. Finally, the correlation between changes of brain and serum BDNF and cognitive functions following morphine exposure needs further research. Copyright © 2017 Elsevier B.V. All rights reserved.

Flibanserin stimulated partner grooming reflects brain metabolism changes in female marmosets

PubMed Central

Converse, Alexander K.; Aubert, Yves; Allers, Kelly A.; Sommer, Bernd; Abbott, David H.

2017-01-01

Introduction Female Sexual Interest and Arousal Disorder (FSIAD) is personally distressing for women. To better understand the mechanism of the candidate therapeutic, flibanserin, we determined its effects on an index of brain glucose metabolism. Aim We hypothesized that chronic treatment with flibanserin would alter metabolism in brain regions associated with serotonergic function and female sexual behavior. Methods In a crossover design, eight adult female common marmosets (Calithrix jacchus) received daily flibanserin or vehicle. After 7–12 weeks of treatment, the glucose metabolism radiotracer FDG was administered to each female immediately prior to 30 min of interaction with her male pairmate, after which females were anesthetized and imaged by PET. Whole-brain normalized images were analyzed with anatomically defined regions of interest. Whole brain voxelwise mapping was used to explore treatment effects. Correlations were examined between alterations in metabolism and pairmate social grooming. Main Outcome Measures Changes in metabolism associated with flibanserin were determined for dorsal raphe (DR), medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus (VMH), and field CA1 of hippocampus. Results In response to chronic flibanserin, metabolism in mPOA declined, and this reduction correlated with increases in pairmate grooming. A cluster of voxels in frontal cortico-limbic regions exhibited reduced metabolism in response to flibanserin and overlapped with a voxel cluster in which reductions in metabolism correlated with increases in pairmate grooming. Finally, reductions in mPOA metabolism correlated with increases in metabolism in a cluster of voxels in somatosensory cortex. Conclusions Taken together, these results suggest that flibanserin-induced reductions in female mPOA neural activity increase intimate affiliative behavior with male pairmates. PMID:26635207

Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

PubMed

Sagae, Sara Cristina; Grassiolli, Sabrina; Raineki, Charlis; Balbo, Sandra Lucinei; Marques da Silva, Ana Carla

2011-11-01

Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females.

Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

PubMed

Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

2018-03-15

Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model

NASA Technical Reports Server (NTRS)

Thierry-Palmer, Myrtle; Cephas, Stacy; Cleek, Tammy; Sayavongsa, Phouyong; Arnaud, Sara B.

2003-01-01

Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.

MRI Reveals Edema in Larynx (But Not in Brain) During Anaphylactic Hypotension in Anesthetized Rats

PubMed Central

Toyota, Ichiro; Tanida, Mamoru; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-01-01

Purpose Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Methods Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Results Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Conclusion Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain. PMID:24179686

MRI reveals edema in larynx (but not in brain) during anaphylactic hypotension in anesthetized rats.

PubMed

Toyota, Ichiro; Tanida, Mamoru; Shibamoto, Toshishige; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-11-01

Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain.

Changes in geometrical and biomechanical properties of immature male and female rat tibia

NASA Technical Reports Server (NTRS)

Zernicke, Ronald F.; Hou, Jack C.-H.; Vailas, Arthur C.; Nishimoto, Mitchell; Patel, Sanjay

1990-01-01

The differences in the geometry and mechanical properties of immature male and female rat tibiae were detailed in order to provide comparative data for spaceflight, exercise, or disease experiments that use immature rats as an animal model. The experiment focuses on the particularly rapid period of growth that occurs in the Sprague-Dawley rat between 40 and 60 d of age. Tibial length and middiaphysical cross-sectional data were analyzed for eight different groups of rats according to age and sex, and tibial mechanical properties were obtained via three-point bending tests to failure. Results indicate that, during the 15 d period of rapid growth, changes in rat tibial geometry are more important than changes in bone material properties for influencing the mechanical properties of the tibia. Male tibiae changed primarily in structural properties, while in the female rats major changes in mechanical properties of the tibia were only attributable to changes in the structural properties of the bone.

Further refinement of the Escherichia coli brain abscess model in rat.

PubMed

Nazzaro, J M; Pagel, M A; Neuwelt, E A

1992-09-01

The rat brain abscess model provides a substrate for the modeling of delivery of therapeutic agents to intracerebral mass lesions. We now report refinement of the Escherichia coli brain abscess model in rat. A K1 surface antigen-negative E. coli isolated from human blood culture was stereotaxically inoculated into deep brain sites. Histopathologic analyses and quantitative cultures demonstrated the consistent production of lesions. No animal in this consecutive series developed meningitis, ventriculitis or sepsis. By contrast, prior experience with E. coli abscess production resulted in 25% failure rate of abscess production or death from sepsis. This improvement in the model may be attributable to specific characteristics of the bacteria used, modification of the inoculation method or the intracerebral placement technique. The present work suggests a reliable and consistent brain abscess model, which may be further used to study brain suppuration.

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

PubMed

Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

2013-06-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

PubMed Central

Kolosova, Nataliya G.; Vitovtov, Anton O.; Muraleva, Natalia A; Akulov, Andrey E.; Stefanova, Natalia A.; Blagosklonny, Mikhail V.

2013-01-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span in C elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wistar rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging. PMID:23817674

The effect of butylphthalide on the brain edema, blood-brain barrier of rats after focal cerebral infarction and the expression of Rho A.

PubMed

Hu, Jinyang; Wen, Qingping; Wu, Yue; Li, Baozhu; Gao, Peng

2014-06-01

The aim of this study was to explore the effect of butylphthalide on the brain edema, blood-brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague-dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood-brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood-brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood-brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood-brain barrier, and decrease the expression of Rho A around the infarction.

Effects of Mucuna pruriens on Free Fatty Acid Levels and Histopathological Changes in the Brains of Rats Fed a High Fructose Diet.

PubMed

Akgun, Bekir; Sarı, Aysel; Ozturk, Sait; Erol, Fatih Serhat; Ozercan, Ibrahim Hanifi; Ulu, Ramazan

2017-01-01

To investigate free fatty acid levels and histopathological changes in the brain of rats fed a high fructose diet (HFrD) and to evaluate the effects of Mucuna pruriens, known to have antidiabetic activity, on these changes. The study comprised 28 mature female Wistar rats. The rats were divided into 4 groups, each included 7 rats. Group 1: control; group 2: fed an HFrD; group 3: fed normal rat chow and M. pruriens; group 4: fed an HFrD and M. pruriens for 6 weeks. At the end of 6 weeks, the rats were decapitated, blood and brain tissues were obtained. Serum glucose and triglyceride levels were measured. Free fatty acid levels were measured in 1 cerebral hemisphere of each rat and histopathological changes in the other. The Mann-Whitney U test was used to compare quantitative continuous data between 2 independent groups, and the Kruskal-Wallis test was used to compare quantitative continuous data between more than 2 independent groups. Arachidonic acid and docosahexaenoic acid levels were significantly higher in group 2 than in group 1 (p < 0.05). Free arachidonic acid and docosahexaenoic acid levels in group 4 were significantly less than in group 2 (p < 0.05). Histopathological examination of group 2 revealed extensive gliosis, neuronal hydropic degeneration, and edema. In group 4, gliosis was much lighter than in group 2, and edema was not observed. Neuronal structures in group 4 were similar to those in group 1. The HFrD increased the levels of free arachidonic acid and docosahexaenoic acid probably due to membrane degradation resulting from possible oxidative stress and inflammation in the brain. The HFrD also caused extensive gliosis, neuronal hydropic degeneration, and edema. Hence, M. pruriens could have therapeutic effects on free fatty acid metabolism and local inflammatory responses in the brains of rats fed an HFrD. © 2017 The Author(s) Published by S. Karger AG, Basel.

Effects of Mucuna pruriens on Free Fatty Acid Levels and Histopathological Changes in the Brains of Rats Fed a High Fructose Diet

PubMed Central

Akgun, Bekir; Sarı, Aysel; Ozturk, Sait; Erol, Fatih Serhat; Ozercan, Ibrahim Hanifi; Ulu, Ramazan

2018-01-01

Objective To investigate free fatty acid levels and histopathological changes in the brain of rats fed a high fructose diet (HFrD) and to evaluate the effects of Mucuna pruriens, known to have antidiabetic activity, on these changes. Materials and Methods The study comprised 28 mature female Wistar rats. The rats were divided into 4 groups, each included 7 rats. Group 1: control; group 2: fed an HFrD; group 3: fed normal rat chow and M. pruriens; group 4: fed an HFrD and M. pruriens for 6 weeks. At the end of 6 weeks, the rats were decapitated, blood and brain tissues were obtained. Serum glucose and triglyceride levels were measured. Free fatty acid levels were measured in 1 cerebral hemisphere of each rat and histopathological changes in the other. The Mann-Whitney U test was used to compare quantitative continuous data between 2 independent groups, and the Kruskal-Wallis test was used to compare quantitative continuous data between more than 2 independent groups. Results Arachidonic acid and docosahexaenoic acid levels were significantly higher in group 2 than in group 1 (p < 0.05). Free arachidonic acid and docosahexaenoic acid levels in group 4 were significantly less than in group 2 (p < 0.05). Histopathological examination of group 2 revealed extensive gliosis, neuronal hydropic degeneration, and edema. In group 4, gliosis was much lighter than in group 2, and edema was not observed. Neuronal structures in group 4 were similar to those in group 1. Conclusions The HFrD increased the levels of free arachidonic acid and docosahexaenoic acid probably due to membrane degradation resulting from possible oxidative stress and inflammation in the brain. The HFrD also caused extensive gliosis, neuronal hydropic degeneration, and edema. Hence, M. pruriens could have therapeutic effects on free fatty acid metabolism and local inflammatory responses in the brains of rats fed an HFrD. PMID:28898884

Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats.

PubMed

Santoru, Francesca; Berretti, Roberta; Locci, Andrea; Porcu, Patrizia; Concas, Alessandra

2014-09-01

Allopregnanolone is a neurosteroid involved in depression, memory, social, and sexual behavior. We have previously demonstrated that treatment with a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds frequently used in hormonal contraception, decreased brain allopregnanolone concentrations. These changes may contribute to some of the emotional and sexual disorders observed in hormonal contraceptive users. We thus examined whether the reduction in allopregnanolone concentrations induced by long-term EE/LNG administration was associated with altered emotional, learning, social, and sexual behaviors. Rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to behavioral tests 24 h after the last administration. EE/LNG treatment reduced immobility behavior in the forced swim test, without affecting sucrose preference and spatial learning and memory. In the resident-intruder test, EE/LNG-treated rats displayed a decrease in dominant behaviors associated with a reduction in social investigation. In the paced mating test, EE/LNG treated rats showed a reduction in proceptive behaviors, while the lordosis quotient was not affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats increased sexual activity and cerebrocortical allopregnanolone concentrations. Prior administration of finasteride decreased allopregnanolone concentrations and abolished the increase in proceptivity induced by progesterone administration. The decrease in brain allopregnanolone concentrations induced by EE/LNG treatment is associated with a reduction in social behavior and sexual motivation in female rats. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.

Transcranial Photoacoustic Measurements of Cold-Injured Brains in Rats

NASA Astrophysics Data System (ADS)

Ueda, Yoshinori; Sato, Shunichi; Hasegawa, Makoto; Nawashiro, Hiroshi; Saitoh, Daizoh; Shima, Katsuji; Ashida, Hiroshi; Obara, Minoru

2005-09-01

We performed transcranial photoacoustic measurements of cold-injured brains in rats. Before inducing injury, a signal peak was observed at two locations corresponding to the surfaces of the skull and brain, while after injury, a third peak appeared at a location corresponding to the back surface of the skull; the third peak was found to be caused by subdural hematoma. The signal peak for the brain surface shifted to a deeper region with elapse of time after injury, indicating deformation of the brain. These findings suggest that small hemorrhage and morphological change of the brain can be transcranially detected by photoacoustic measurement.

Flutamide-mediated androgen blockade evokes osteopenia in the female rat.

PubMed

Goulding, A; Gold, E

1993-06-01

Androgens are believed to play a role in building and maintaining bone in the female, as well as in the male. The antiandrogen drug flutamide inhibits responses to androgens from both the gonads and the adrenals. Antiandrogens prevent androgens stimulating bone cell proliferation and differentiation in vitro, but effects of androgen blockade on bone metabolism in vivo have not been tested. The present study was undertaken to determine whether androgen blockade with flutamide (15 mg/kg body weight orally daily) would influence bone turnover or bone composition (1) in female rats with intact ovaries and (2) in rats made estrogen-deficient with the luteinizing hormone releasing hormone (LHRH) agonist, buserelin (25 micrograms/kg body weight per day SC). Four groups of rats with 45Ca-labeled skeletons were studied for 4 weeks: group A, placebo; group B, buserelin; group C, flutamide; group D, flutamide+buserelin. Total-body calcium values (mean +/- SD) were (mg) 2007 +/- 109, 1779 +/- 138 (P < 0.01 versus group A), 1818 +/- 140 (P < 0.01 versus group A), and 1690 +/- 75 (P < 0.01 versus group A) in groups A-D, respectively. Thus both buserelin and flutamide induced osteopenia. Skeletal 45Ca changes suggested buserelin-mediated estrogen deficiency bone loss was due to increased bone resorption, but flutamide-mediated androgen deficiency bone thinning was caused principally by reduced bone formation. These findings support the view that androgens play an important role in preserving bone mass in the female rat. Importantly, adequate estrogen status did not compensate for flutamide-mediated osteopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.

PubMed

Thibodeau, Rachel B; Ornelas, Laura C; Romero, Jordan; Memos, Nicoletta; Scheible, Matthew; Avila, Alfred; Schumacher, Abby; Navarro, April; Zimmermann, Karen; Cuenod, Bethany A; Frohardt, Russell J; Guarraci, Fay A

2013-02-01

The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Factors influencing fluoxetine-induced sexual dysfunction in female rats

PubMed Central

Adams, Sarah; Heckard, Danyeal; Hassell, James; Uphouse, Lynda

2012-01-01

Treatment with selective serotonin reuptake inhibitors, such as fluoxetine, produces sexual side effects with low sexual desire being the most prevalent effect in females. In few studies have preclinical models for such antidepressant-induced sexual dysfunction been fruitful. In the current manuscript, the effects of fluoxetine on multiple measures of female sexual motivation and sexual receptivity were examined. Ovariectomized, Fischer rats were primed with 10 μg estradiol benzoate and 500 μg progesterone. Partner preference, active investigation of the male, and measures of sexual behavior were examined after injection with 15 mg/kg fluoxetine. Factors (pretesting for sexual behavior, size of the test arena, non-contact time with a male) that differ among experiments designed to study antidepressant-induced female rat sexual dysfunction were studied. The male preference ratio was not affected by fluoxetine treatment but active investigation of the male was reduced; lordosis behavior was inhibited and pretesting for sexual receptivity amplified fluoxetine's inhibition; size of the testing arena or non-contact experience with the male had no effect. Regardless of test condition, when given the opportunity to escape from the male, fluoxetine-treated females displayed escape behavior. Measures of male preference and active investigation, but not lordosis behavior, appeared to be affected by fluoxetine's impact on activity. The collective data provided a behavioral profile of fluoxetine-induced sexual dysfunction. These findings reinforce the value of multiple measures when attempting to model antidepressant-induced female sexual dysfunction. PMID:22835821

Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain.

PubMed

Marco, Eva M; Echeverry-Alzate, Victor; López-Moreno, Jose Antonio; Giné, Elena; Peñasco, Sara; Viveros, Maria Paz

2014-09-01

The endocannabinoid system is involved in several physiological and pathological states including anxiety, depression, addiction and other neuropsychiatric disorders. Evidence from human and rodent studies suggests that exposure to early life stress may increase the risk of psychopathology later in life. Indeed, maternal deprivation (MD) (24 h at postnatal day 9) in rats induces behavioural alterations associated with depressive-like and psychotic-like symptoms, as well as important changes in the endocannabinoid system. As most neuropsychiatric disorders first appear at adolescence, and show remarkable sexual dimorphisms in their prevalence and severity, in the present study, we analysed the gene expression of the main components of the brain cannabinoid system in adolescent (postnatal day 46) Wistar male and female rats reared under standard conditions or exposed to MD. For this, we analysed, by real-time quantitative PCR, the expression of genes encoding for CB1 and CB2 receptors, TRPV1 and GPR55 (Cnr1, Cnr2a, Cnr2b, Trpv1, and Gpr55), for the major enzymes of synthesis, N-acyl phosphatidyl-ethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL) (Nape-pld, Dagla and Daglb), and degradation, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) (Faah, Magl and Cox-2), in specific brain regions, that is, the frontal cortex, ventral and dorsal striatum, dorsal hippocampus and amygdala. In males, MD increased the genetic expression of all the genes studied within the frontal cortex, whereas in females such an increase was observed only in the hippocampus. In conclusion, the endocannabinoid system is sensitive to early life stress at the gene expression level in a sex-dependent and region-dependent manner, and these changes are already evident in the adolescent brain.

Volumetric abnormalities of the brain in a rat model of recurrent headache.

PubMed

Jia, Zhihua; Tang, Wenjing; Zhao, Dengfa; Hu, Guanqun; Li, Ruisheng; Yu, Shengyuan

2018-01-01

Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks' stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.

Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain.

PubMed

Manthey, Daniela; Asimiadou, Stella; Stefovska, Vanya; Kaindl, Angela M; Fassbender, Jessica; Ikonomidou, Chrysanthy; Bittigau, Petra

2005-06-01

Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children can cause cognitive impairment. One mechanism implicated in the development of neurocognitive deficits is a pathologic enhancement of physiologically occurring apoptotic neuronal death in the developing brain. We investigated whether the newer antiepileptic drug levetiracetam (LEV) and the older antiepileptic drug sulthiame (SUL) have neurotoxic properties in the developing rat brain. SUL significantly enhanced neuronal death in the brains of rat pups ages 0 to 7 days at doses of 100 mg/kg and above, whereas LEV did not show this neurotoxic effect. Dosages of both drugs used in the context of this study comply with an effective anticonvulsant dose range applied in rodent seizure models. Thus, LEV is an AED which lacks neurotoxicity in the developing rat brain and should be considered in the treatment of epilepsy in pregnant women, infants, and toddlers once general safety issues have been properly addressed.

Effect of acute progestational hypoxia on the content of biogenic amines in the brain of albino rat pups: Peptide correction.

PubMed

Maslova, M V; Graf, A V; Sokolova, N A; Goncharenko, E N; Shestakova, S V; Kudryashova, N Yu; Andreeva, L A

2003-08-01

We studied the effect of exposure to acute hypobaric hypoxia in the progestational period on the content of biogenic amines in the brainstem and cerebral cortex in rat pups of different age. The possibility of correcting hypoxia-induced changes with regulatory peptides was evaluated. We found that early antenatal hypoxia disturbs maturation of catecholaminergic systems in the brain. It should be emphasized that the differences from the control varied depending on the age of rat pups. Single intranasal administration of Semax heptapeptides and beta-casomorphine-7 to pregnant females prevented changes in the content of biogenic amines in CNS of the offspring during postnatal ontogeny.

The Ontogeny of Exploratory Behavior in Male and Female Adolescent Rats (Rattus norvegicus)

PubMed Central

Lynn, Debra A; Brown, Gillian R

2009-01-01

During adolescence, rats gain independence from their mothers and disperse from the natal burrow, with males typically dispersing further than females. We predicted that, if dispersal patterns are associated with responsiveness to novelty, exploratory behavior in novel environments would increase across adolescence, and males would explore more than females. Alternatively, females might explore more than males, if females are more motivated than males to learn about the immediate environment or if females have poorer spatial abilities than males. Twenty-five male and 21 female rats were exposed to two novel environments (open field and elevated plus-maze) during early, mid-, or late adolescence. Total locomotion and amount of exploration directed towards aversive areas increased across adolescence, even when body weight was included as a covariate. Female adolescents locomoted more and spent more time exploring aversive areas than males. Developmental changes in neural function potentially underlie age and sex differences in exploratory behavior. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 513–520, 2009. PMID:19582791

The ontogeny of exploratory behavior in male and female adolescent rats (Rattus norvegicus).

PubMed

Lynn, Debra A; Brown, Gillian R

2009-09-01

During adolescence, rats gain independence from their mothers and disperse from the natal burrow, with males typically dispersing further than females. We predicted that, if dispersal patterns are associated with responsiveness to novelty, exploratory behavior in novel environments would increase across adolescence, and males would explore more than females. Alternatively, females might explore more than males, if females are more motivated than males to learn about the immediate environment or if females have poorer spatial abilities than males. Twenty-five male and 21 female rats were exposed to two novel environments (open field and elevated plus-maze) during early, mid-, or late adolescence. Total locomotion and amount of exploration directed towards aversive areas increased across adolescence, even when body weight was included as a covariate. Female adolescents locomoted more and spent more time exploring aversive areas than males. Developmental changes in neural function potentially underlie age and sex differences in exploratory behavior. (c) 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 513-520, 2009.

Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

ERIC Educational Resources Information Center

Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.

2008-01-01

Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or…

Beneficial Effects of Highly Palatable Food on the Behavioral and Neural Adversities induced by Early Life Stress Experience in Female Rats.

PubMed

Kim, Jin Young; Lee, Jong-Ho; Kim, Doyun; Kim, Soung-Min; Koo, JaeHyung; Jahng, Jeong Won

2015-01-01

This study examined the effects of highly palatable food during adolescence on the psycho-emotional and neural disturbances caused by early life stress experience in female rats. Female Sprague-Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (MS) or left undisturbed (NH). Half of MS females received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28. Pups were subjected to the behavioral tests during young adulthood. The plasma corticosterone response to acute stress, ΔFosB and brain-derived neurotrophic factor (BDNF) levels in the brain regions were analyzed. Total caloric intake and body weight gain during the whole experimental period did not differ among the experimental groups. Cookie access during adolescence and youth improved anxiety-/depression-like behaviors by MS experience. ΔFosB expression was decreased, but BDNF was increased in the nucleus accumbens of MS females, and ΔFosB expression was normalized and BDNF was further increased following cookie access. Corticosterone response to acute stress was blunted by MS experience and cookie access did not improve it. Results suggest that cookie access during adolescence improves the psycho-emotional disturbances of MS females, and ΔFosB and/or BDNF expression in the nucleus accumbens may play a role in its underlying neural mechanisms.

Perinatal testosterone contributes to mid-to-post pubertal sex differences in risk for binge eating in male and female rats.

PubMed

Culbert, Kristen M; Sinclair, Elaine B; Hildebrandt, Britny A; Klump, Kelly L; Sisk, Cheryl L

2018-02-01

Exposure to testosterone early in life may contribute to sex differences and pubertal changes in risk for eating pathology (i.e., females > males, after pubertal onset). Specifically, perinatal testosterone permanently alters brain structure/function and drives the masculinization of several sex-differentiated behaviors. However, the effects of perinatal testosterone are often not evident until puberty when increases in gonadal hormones activate the expression of sex typical behavior, including eating behaviors (e.g., chow intake; saccharin preference) in rodents. Despite perinatal testosterone's masculinizing effects on general feeding behavior, it remains unknown if perinatal testosterone exposure contributes to sex differences in pathological eating. The current study addressed this gap by examining whether perinatal testosterone exposure decreases risk for binge eating proneness after pubertal onset in male and female rats. Sprague-Dawley rats (n = 40 oil-treated control females; n = 39 testosterone-treated females; n = 40 oil-treated control males) were followed longitudinally across pre-to-early puberty, mid-to-late puberty, and adulthood. The binge eating prone (BEP)/binge eating resistant (BER) rodent model was used to identify individual differences in binge eating proneness across the dimensional spectrum. As expected, testosterone-treated females and control males showed masculinized (i.e., lower) risk for binge eating as compared to control females, but only after midpuberty. These animal data are significant in suggesting that perinatal testosterone exposure may protect against binge eating and underlie sex differences in binge eating prevalence during and after puberty. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Prenatal androgen excess programs metabolic derangements in pubertal female rats.

PubMed

Yan, Xiaonan; Dai, Xiaonan; Wang, Jing; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

2013-04-01

Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5α-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5-8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30- and 60-min glucose levels than the controls after insulin stimulation during 5-8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development.

The influence of microwave radiation from cellular phone on fetal rat brain.

PubMed

Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui

2012-03-01

The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (P<0.05) found in the contents of SOD, GSH-Px, and MDA in GM and GH; the contents of SOD and GSH-Px decreased and the content of MDA increased. The significant content differences of NE and DA were found in fetal rat brains in GL and GH groups, with the GL group increased and the GH group decreased. Through this study, we concluded that receiving a certain period of microwave radiation from cellular phones during pregnancy has certain harm on fetal rat brains.

[New data on olfactory control of estral receptivity of female rats].

PubMed

Satli, M A; Aron, C

1976-03-01

Olfactory bulb deprivation increased sexual receptivity in 4-day cyclic female rats on the late afternoon of prooestrus (6-7, p.m.). The proportion of receptive females was higher in bulbectomized (B) than in sham operated (SH) animals. On the contrary the same proportion of B and SH females mated in the evening of prooestrus (10. 30-11. 30 p.m.). An increased lordosis quotient was observed in the B females at either of these two stages of the cycle.

Investigation of the Effects of Subchronic Low Dose Oral Exposure to Bisphenol A (BPA) and Ethinyl Estradiol (EE) on Estrogen Receptor Expression in the Juvenile and Adult Female Rat Hypothalamus

PubMed Central

Rebuli, Meghan E.; Cao, Jinyan; Sluzas, Emily; Delclos, K. Barry; Camacho, Luísa; Lewis, Sherry M.; Vanlandingham, Michelle M.; Patisaul, Heather B.

2014-01-01

Concerns have been raised regarding the long-term impacts of early life exposure to the ubiquitous environmental contaminant bisphenol A (BPA) on brain organization. Because BPA has been reported to affect estrogen signaling, and steroid hormones play a critical role in brain sexual differentiation, there is also concern that BPA exposure could alter neural sex differences. Here, we examine the impact of subchronic exposure from gestation to adulthood to oral doses of BPA below the current no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day on estrogen receptor (ESR) expression in sexually dimorphic brain regions of prepubertal and adult female rats. The dams were gavaged daily with vehicle (0.3% carboxymethylcellulose), 2.5, 25, 260, or 2700 μg BPA/kg bw/day, or 0.5 or 5.0 μg ethinyl estradiol (EE)/kg bw/day from gestational day 6 until labor began. Offspring were then gavaged directly from the day after birth until the day before scheduled sacrifice on postnatal days 21 or 90. Using in situ hybridization, one or more BPA doses produced significant decreases in Esr1 expression in the juvenile female rat anteroventral periventricular nucleus (AVPV) of the hypothalamus and significant decreases in Esr2 expression in the adult female rat AVPV and medial preoptic area (MPOA), relative to vehicle controls. BPA did not simply reproduce EE effects, indicating that BPA is not acting solely as an estrogen mimic. The possible consequences of long-term changes in hypothalamic ESR expression resulting from subchronic low dose BPA exposure on neuroendocrine effects are discussed and being addressed in ongoing, related work. PMID:24752507

Distribution of renin activity and angiotensinogen in rat brain. Effects of dietary sodium chloride intake on brain renin.

PubMed Central

Genain, C P; Van Loon, G R; Kotchen, T A

1985-01-01

The purpose of this study was to investigate the biochemistry and the regulation of the brain renin-angiotensin system in the Sprague-Dawley rat. Renin activity and angiotensinogen concentrations (direct and indirect radioimmunoassays) were measured in several brain areas and in neuroendocrine glands. Regional renin activities were measured in separate groups of rats on high and low NaCl diets. Mean tissue renin activities ranged from 2.2 +/- 0.6 to 54.4 +/- 19.7 fmol/mg protein per h (mean of 7 +/- SD), with the highest amounts in pineal, pituitary, and pons-medulla. NaCl depletion increased renin activity in selected regions; based on estimates of residual plasma contamination (despite perfusion of brains with saline), increased renin activity of pineal gland and posterior pituitary was attributed to higher plasma renin. To eliminate contamination by plasma renin, 16-h-nephrectomized rats were also studied. In anephric rats, NaCl depletion increased renin activity by 92% in olfactory bulbs and by 97% in anterior pituitary compared with NaCl-replete state. These elevations could not be accounted for by hyperreninemia. Brain renin activity was low and was unaffected by dietary NaCl in amygdala, hypothalamus, striatum, frontal cortex, and cerebellum. In contrast to renin, highest angiotensinogen concentrations were measured in hypothalamus and cerebellum. Overall, angiotensinogen measurements with the direct and the indirect assays were highly correlated (n = 56, r = 0.96, P less than 0.001). We conclude that (a) NaCl deprivation increases renin in olfactory bulbs and anterior pituitary of the rat, unrelated to contamination by plasma renin; and (b) the existence of angiotensinogen, the precursor of angiotensins, is demonstrated by direct radioimmunoassay throughout the brain and in neuroendocrine glands. PMID:3902894

[Stimulation of D1-receptors improves passive avoidance learning of female rats during ovary cycle].

PubMed

Fedotova, Iu O; Sapronov, N S

2012-01-01

The involvement of D1-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. SKF-38393 (0,1 mg/kg, i.p.), D1-receptor agonist and SCH-23390 (0,1 mg/kg, i.p.), D1-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic SKF-3839 administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals, but failed to change the dynamics of spatial learning in Morris water maze. Chronic SCH-23390 administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D1-receptors in learning/memory processes during ovary cycle in the adult female rats.

Female Mice are Resistant to Fabp1 Gene Ablation-Induced Alterations in Brain Endocannabinoid Levels.

PubMed

Martin, Gregory G; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K; Dangott, Lawrence J; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J; Kier, Ann B; Schroeder, Friedhelm

2016-09-01

Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in the brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing EC, i.e. arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: (1) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; (2) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or (3) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO).

FEMALE MICE ARE RESISTANT TO Fabp1 GENE ABLATION-INDUCED ALTERATIONS IN BRAIN ENDOCANNABINOID LEVELS

PubMed Central

Martin, Gregory G.; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K.; Dangott, Lawrence J.; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J.; Kier, Ann B.; Schroeder, Friedhelm

2017-01-01

Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing ECs, i.e arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: i) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; ii) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or iii) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO). PMID:27450559

[Antitumor effect of baicalin on rat brain glioma].

PubMed

Hu, Yong-zhen; Wang, Dian-hong; Luan, Yu; Gong, Hai-dong

2013-01-01

To investigate the therapeutic mechanism of baicalin on rat brain glioma. Deep brain glioma models were established by injection of glioma cell line C6 cells into the brain of Wistar rats. The rats at 7 days after modeling were randomly divided into tumor control group (0.9% NaCl solution 30 mg×kg(-1)×d(-1) gavage)and experimental groups. The experimental rats was divided into 3 groups: low dose group (50 mg×kg(-1)×d(-1)), middle dose group (100 mg×kg(-1)×d(-1)) and high dose group (200 mg×kg(-1)×d(-1)), given the baicalin by gavage. Pathological and electron microscopic changes were observed. The expressions of p53 and Bcl-2 were determined by immunohistochemistry, and the changes of MRI, the average survival time and body weight of the rats in each group after treatments were analyzed. Compared with the control group, the tumor diameter and volume of high dose group rats before sacrifice were significantly reduced (P < 0.01), and the survival time was significantly prolonged (P < 0.01). Immunohistochemistry revealed strong positive expression rate of mutant p53 (84.47 ± 3.74)% and moderately positive rate (47.28 ± 2.38)% in the control group, significantly higher than that in the negative group (12.91 ± 1.07)% (P < 0.01). The positive rate of mutant p53 of the high dose group was (46.42 ± 2.19)%, significantly lower than that of the control group (84.47 ± 3.74)% (P < 0.01). The expression rate of Bcl-2 in the control group was strongly positive (86.51 ± 4.17)% and moderate positive (48.19 ± 2.11)%, significantly higher than that of the negative group (10.36 ± 1.43)% (P < 0.01). Electron microscopy revealed that baicalin caused damages of the cell nuclei and organelles in the gliomas. Baicalin has significant inhibitory effect on glioma in vivo, and its mechanism may be related to cell apoptosis induced by down-regulated expression of mutant p53, but not related with Bcl-2 expression.

Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

PubMed

Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

2014-08-21

Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

PubMed

Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Anti-Correlated Cortical Networks of Intrinsic Connectivity in the Rat Brain

PubMed Central

Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

Abstract In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline “DMN-like” network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans. PMID:23919836

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury.

PubMed

Tu, Tsang-Wei; Lescher, Jacob D; Williams, Rashida A; Jikaria, Neekita; Turtzo, L Christine; Frank, Joseph A

2017-01-01

Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

PubMed Central

Lescher, Jacob D.; Williams, Rashida A.; Jikaria, Neekita; Turtzo, L. Christine; Frank, Joseph A.

2017-01-01

Abstract Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate

Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

PubMed Central

Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

2016-01-01

Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

A multiscale cerebral neurochemical connectome of the rat brain

PubMed Central

Schöttler, Judith; Ercsey-Ravasz, Maria; Cosa-Linan, Alejandro; Varga, Melinda; Toroczkai, Zoltan; Spanagel, Rainer

2017-01-01

Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing. By using advanced data mining, supervised machine learning, and network analysis, this study integrates over 5 decades of neuroanatomical investigations into a multiscale, multilayer neurochemical connectome of the rat brain. This neurochemical connectivity database (ChemNetDB) is supported by comprehensive systematically-determined receptor distribution maps. The rat connectome has an onion-type structural organization and shares a number of structural features with mesoscale connectomes of mouse and macaque. Furthermore, we demonstrate that extremal values of graph theoretical measures (e.g., degree and betweenness) are associated with evolutionary-conserved deep brain structures such as amygdala, bed nucleus of the stria terminalis, dorsal raphe, and lateral hypothalamus, which regulate primitive, yet fundamental functions, such as circadian rhythms, reward, aggression, anxiety, and fear. The ChemNetDB is a freely available resource for systems analysis of motor, sensory, emotional, and cognitive information processing. PMID:28671956

Cafeteria feeding induces interleukin-1beta mRNA expression in rat liver and brain.

PubMed

Hansen, M K; Taishi, P; Chen, Z; Krueger, J M

1998-06-01

intake affects gut-immune function and can provide a strong intestinal antigen challenge resulting in activation of host defense mechanisms in the digestive system. Previously, we showed that feeding rats a cafeteria diet increases non-rapid eye movement sleep by a subdiaphragmatic mechanism. Food intake and sleep regulation and the immune system share the regulatory molecule interleukin-1beta (IL-1beta). Thus this study examined the effects of a cafeteria diet on IL-1beta mRNA and IL-1 receptor accessory protein (IL-1RAP) mRNA expression in rat liver and brain. Rats were fed normal rat chow or a palatable diet consisting of bread, chocolate, and shortbread cookies (cafeteria diet). After 3 days, midway between the light period of the light-dark cycle, rats were killed by decapitation. Feeding rats a cafeteria diet resulted in increased IL-1beta mRNA expression in the liver and hypothalamus compared with rats fed only the normal rat chow. In addition, cafeteria feeding decreased IL-1RAP mRNA levels in the liver and brain stem. These results indicate that feeding has direct effects on cytokine production and together with other data suggest that the increased sleep that accompanies increased feeding may be the result of increased brain IL-1beta. These results further suggest that cytokine-to-brain communication may be important in normal physiological conditions, such as feeding, as well as being important during inflammatory responses.

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats.

PubMed

Sinclair, Elaine B; Culbert, Kristen M; Gradl, Dana R; Richardson, Kimberlei A; Klump, Kelly L; Sisk, Cheryl L

2015-12-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague-Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial prefrontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex

Sprague-Dawley and Fischer female rats differ in acute effects of fluoxetine on sexual behavior.

PubMed

Miryala, Chandra Suma J; Hiegel, Cindy; Uphouse, Lynda

2013-02-01

The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT(1A) receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT(1A) receptors holds for other rat strains is not known. The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT(1A) receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC(50) for inhibition of lordosis behavior was determined. In both the intact and the hormonally primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT(1A) receptor agonist. Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT(1A) receptor agonist. Fluoxetine's inhibition of female rat sexual behavior may involve effects of the SSRI in addition to

Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior

PubMed Central

Miryala, C.S.J.; Hiegel, C.; Uphouse, L.

2012-01-01

Introduction The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT1A receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT1A receptors holds for other rat strains is not known. Aim The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT1A receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Main Outcome Measures Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC50 for inhibition of lordosis behavior was determined. Methods Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Results In both the intact and the hormonally-primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose-dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally-primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT1A receptor agonist. Conclusions Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT1A receptor agonist. Fluoxetine’s inhibition of female rat

Dairy fat blends high in α-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats.

PubMed

Du, Qin; Martin, Jean-Charles; Agnani, Genevieve; Pages, Nicole; Leruyet, Pascale; Carayon, Pierre; Delplanque, Bernadette

2012-12-01

Achieving an appropriate docosahexaenoic acid (DHA) status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how different dietary fat matrices improved DHA content in the brains of both male and female rats. Forty rats of each gender were born from dams fed over gestation and lactation with a low α-linolenic acid (ALA) diet (0.4% of fatty acids) and subjected for 6 weeks after weaning to a palm oil blend-based diet (10% by weight) that provided either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid or to an anhydrous dairy fat blend that provided 1.5% or 2.3% ALA. Fatty acids in the plasma, red blood cells (RBCs) and whole brain were determined by gas chromatography. The 1.5% ALA dairy fat was superior to both the 1.5% ALA palm oil blends for increasing brain DHA (14.4% increase, P<.05), and the 2.3% ALA dairy blend exhibited a further increase that could be ascribed to both an ALA increase and n-6/n-3 ratio decrease. Females had significantly higher brain DHA due to a gender-to-diet interaction, with dairy fats attenuating the gender effect. Brain DHA was predicted with a better accuracy by some plasma and RBC fatty acids when used in combination (R(2) of 0.6) than when used individually (R(2)=0.47 for RBC n-3 docosapentaenoic acid at best). In conclusion, dairy fat blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of postweaning rats. Human applications are worth considering. Copyright © 2012 Elsevier Inc. All rights reserved.

Brain Activation Patterns at Exhaustion in Rats That Differ in Inherent Exercise Capacity

PubMed Central

Foley, Teresa E.; Brooks, Leah R.; Gilligan, Lori J.; Burghardt, Paul R.; Koch, Lauren G.; Britton, Steven L.; Fleshner, Monika

2012-01-01

In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5–15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15–51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines. PMID:23028992

Drug- and cue-induced reinstatement of cannabinoid-seeking behaviour in male and female rats: influence of ovarian hormones.

PubMed

Fattore, L; Spano, M S; Altea, S; Fadda, P; Fratta, W

2010-06-01

Animal and human studies have shown that sex and hormones are key factors in modulating addiction. Previously, we have demonstrated that self-administration of the cannabinoid CB(1) receptor agonist WIN55,212-2 (WIN; 12.5 microg.kg(-1) per infusion) is dependent on sex, intact female rats being more sensitive than males to the reinforcing properties of cannabinoids, and on the oestrous cycle, ovariectomized (OVX) females being less responsive than intact females. This follow-up study investigated whether sex and ovarian function also affect reinstatement of cannabinoid-seeking in rats after exposure to drug or cue priming. After priming with 0.15 or 0.3 mg.kg(-1) WIN, intact female rats exhibited stronger reinstatement than males and OVX females. Responses of intact female rats were higher than those of male and OVX rats even after priming with a drug-associated visual (Light) or auditory (Tone) cue, or a WIN + Light combination. However, latency to the first response did not differ between intact and OVX female rats, and males showed the longest latency to initiate lever-pressing activity. Our study provides compelling evidence for a pivotal role of sex and the oestrous cycle in modulating cannabinoid-seeking, with ovariectomy diminishing drug and cue-induced reinstatement. However, it is possible that sex differences during self-administration training are responsible for sex differences in reinstatement. Finding that not only drug primings but also acute exposure to drug-associated cues can reinstate responding in rats could have significant implications for the development of pharmacological and behavioural treatments of abstinent female and male marijuana smokers.

Diet-induced obesity alters memory consolidation in female rats.

PubMed

Zanini, P; Arbo, B D; Niches, G; Czarnabay, D; Benetti, F; Ribeiro, M F; Cecconello, A L

2017-10-15

Obesity is a multifactorial disease characterized by the abnormal or excessive fat accumulation, which is caused by an energy imbalance between consumed and expended calories. Obesity leads to an inflammatory response that may result in peripheral and central metabolic changes, including insulin and leptin resistance. Insulin and leptin resistance have been associated with metabolic and cognitive dysfunctions. Obesity and some neurodegenerative diseases that lead to dementia affect mainly women. However, the effects of diet-induced obesity on memory consolidation in female rats are poorly understood. Therefore, the aim of this study was to evaluate the effect of a hypercaloric diet on the object recognition memory of female rats and on possible related metabolic changes. The animals submitted to the hypercaloric diet presented a higher food intake in grams and in calories, resulting in increased weight gain and liposomatic index in comparison with the animals exposed to the control diet. These animals presented a memory deficit in the object recognition test and increased serum levels of glucose and leptin. However, no significant differences were found in the serum levels of insulin, TNF-α and IL-1β, in the index of insulin resistance (HOMA), in the hippocampal levels of insulin, TNF-α and IL-1β, as well as on Akt expression or activation in the hippocampus. Our findings indicate that adult female rats submitted to a hypercaloric diet present memory consolidation impairment, which could be associated with diet-induced weight gain and leptin resistance, even without the development of insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats.

PubMed

McDougall, Sanders A; Apodaca, Matthew G; Mohd-Yusof, Alena; Mendez, Adrian D; Katz, Caitlin G; Teran, Angie; Garcia-Carachure, Israel; Quiroz, Anthony T; Crawford, Cynthia A

2018-04-18

Ontogenetic differences in the behavioral responsiveness to cocaine have often been attributed to the maturation of dopaminergic elements (e.g., dopamine transporters, D2 High receptors, receptor coupling, etc.). The purpose of this study was to determine whether ontogenetic changes in cocaine pharmacokinetics might contribute to age-dependent differences in behavioral responsiveness. Male and female neonatal (PD 5), preweanling (PD 10 and PD 20), and adult (PD 70) rats were injected (IP) with cocaine or saline and various behaviors (e.g., locomotor activity, forelimb paddle, vertical activity, head-down sniffing, etc.) were measured for 90 min. In a separate experiment, the dorsal striata of young and adult rats were removed at 10 time points (0-210 min) after IP cocaine administration. Peak cocaine values, cocaine half-life, and dopamine levels were determined using HPLC. When converted to percent of saline controls, PD 5 and PD 10 rats were generally more sensitive to cocaine than older rats, but this effect varied according to the behavior being assessed. Peak cocaine values did not differ according to age or sex, but cocaine half-life in brain was approximately 2 times longer in PD 5 and PD 10 rats than adults. Cocaine pharmacokinetics did not differ between PD 20 and PD 70 rats. Differences in the cocaine-induced behavioral responsiveness of very young rats (PD 5 and PD 10) and adults may be attributable, at least in part, to pharmacokinetic factors; whereas, age-dependent behavioral differences between the late preweanling period and adulthood cannot readily be ascribed to cocaine pharmacokinetics.

Inhibition of rat brain monoamine oxidase by repeated administration of pirlindol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verevkina, I.V.; Asnina, V.V.; Gorkin, V.Z.

1985-10-01

Since pirlindol, like other antidepressants, is used for a long time and since its therapeutic effect usually appears 5-7 days or more after the beginning of treatment, the authors investigate its action on activity of MAO of types A and B in rat brain when administered repeatedly. MAO activity was determined in 50% homogenates of rat brain, made up in 10 mM phosphate buffer, pH 7.4, containing 2% detergent Triton X-100. It is shown that an important role in the antidepressant effect of pirlindol is played by its property of selectively blocking deamination of neurotrans mitters such as serotonin andmore » noradrenalin in the human brain.« less

Female Wistar rats tested during late proestrus or during pregnancy and ovariectomized rats tested after receiving progesterone or allopregnanolone displayed reduced conflict behavior.

PubMed

Molina-Hernandez, Miguel; Perez, Julian Garcia; Olivera Lopez, Jorge Ivan

2002-06-01

In a conflict test based on the rat's choice between an immediate punished reinforcer or a delayed nonpunished reinforcer, anxiolytic drugs increase the number of immediate punished reinforcers. In this study, two hypotheses were tested: first, during late proestrus or during midpregnancy, female rats will display an elevated amount of immediate punished reinforcers; second, ovariectomized rats will display an elevated amount of immediate punished reinforcers when they receive anxiolytic doses of neurosteroids. Thus, female rats (n = 15) were tested repeatedly during late proestrus, diestrus, and pregnancy in the aforementioned conflict task. They displayed an elevated amount of immediate punished reinforcers during late proestrus (P < .05) and during the 14th (P < .05) and 17th (P < .05) days of pregnancy compared to diestrus or 3rd, 7th, or 20th days of pregnancy. Likewise, ovariectomized rats (n = 90) displayed an elevated amount of immediate punished reinforcers compared to control rats only when they received anxiolytic doses of progesterone (1.0-2.0 mg/kg, P < .05) or allopregnanolone (1.0-2.0 mg/kg, P < .05). In conclusion, female rats displayed reduced conflict behavior during late proestrus and pregnancy, or after received anxiolytic doses of neurosteroids.

Effects of long-term construction noise on health of adult female Wistar rats.

PubMed

Zymantiene, J; Zelvyte, R; Pampariene, I; Aniuliene, A; Juodziukyniene, N; Kantautaite, J; Oberauskas, V

2017-03-28

The aim of this study was to investigate the influence of long-term building construction noise from refurbishment, which including vibration, on some physiological parameters and histopathological changes of organs of Wistar rats. Twenty 12 month old female rats were divided into two groups: rats group I (n = 10) were exposed to long-term construction noise and rats group II (n = 10) were kept under normal noise level. Study results revealed that long-term construction noise from building refurbishment has an influence on body weight, haematological and some serum biochemical parameters affects caecal microbiota, and causes histopathological changes in the organs of adult female Wistar rats. It was noticed that rats in group I exihibited significantly higher mean values for total protein, albumin and lower values for glucose, AST, ALT, blood urea nitrogen, haematological and caecal microbiota parameters than rats in group II. The most common pathologies were determined in the kidney, liver and lungs. Other observed pathologies were lymphadenopathy, catarrhal inflammation of the intestines, spleen hyperplasia and mammary gland adenofibroma. Single cases were subcutaneous fibroma in the thoracic region, abortus with uterine inflammation and thymus hyperplasia with formation of cysts were found.

The effect of electromagnetic radiation on the rat brain: an experimental study.

PubMed

Eser, Olcay; Songur, Ahmet; Aktas, Cevat; Karavelioglu, Ergun; Caglar, Veli; Aylak, Firdevs; Ozguner, Fehmi; Kanter, Mehmet

2013-01-01

The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem. EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

Age-related changes in dorsal root ganglia, circulating and vascular calcitonin gene-related peptide (CGRP) concentrations in female rats: Effect of female sex steroid hormones

PubMed Central

Gangula, Pandu R.R.; Chauhan, Madhu; Reed, Luckey; Yallampalli, Chandra

2009-01-01

The aim of the present study is to investigate whether immunoreactive (I) calcitonin gene-related peptide (CGRP) content is decreased in plasma and mesenteric arteries (resistance arteries) in middle-aged rats and if so, whether sex steroid hormones enhance I-CGRP in middle-aged female rats. We also examined whether vascular CGRP receptor components, calcitonin receptor like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) are elevated by sex steroid hormones treatment in middle-aged female rats. Young adult (3 months old) and middle-aged (10–12 months old) ovariectomized rats were treated subcutaneously with estradiol-17β (E2; 2 mg), progesterone (P4; 5 mg), E2 +P4 (2 mg + 20 mg) or placebo (control). Radioimmunoassay and Western blot analysis were performed to measure I-CGRP content and CGRP receptor components in dorsal root ganglia (DRG), in resistance arteries and in plasma. Immunofluorescent staining methods were employed to determine cellular localization of CRLR, RAMP1 in resistance arteries. Our data demonstrated that I-CGRP content was significantly (p < 0.05) lower in the plasma and resistance arteries of middle-aged female rats compared to young controls. Both RAMP1 and CRLR were concentrated in vascular endothelium and the underlying smooth muscle cells. RAMP1 but not CRLR appeared to be decreased in middle-aged rat vasculature. Chronic perfusion of sex steroid hormones to ovariectomized rats: (1) significantly (p < 0.05) elevated I-CGRP in the DRG and in the plasma, and (2) significantly elevated RAMP1 (p < 0.05) but did not alter CRLR in resistance arteries. These data suggest that female sex steroid treatment enhances I-CGRP and its receptors, and thus regulate the blood pressure in aged female rats. PMID:19429067

Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

PubMed Central

Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

2015-01-01

Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5–6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

Short and long effects of Citrullus colocynthis L. on reproductive system and fertility in female Spague-Dawley rats.

PubMed

Qazan, Walid Sh; Almasad, Motasem M; Daradka, Haytham

2007-08-15

Aim of this study is to investigate the toxic effects of Citrullus colocynthis L. (400 mg/kg/body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and Citrullus colocynthis L. were intraperitoneally injected to experimental animals in dose of 400 mg/kg/body wight. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using students t and Chi-square tests. The effect of Citrullus colocynthis L. exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Citrullus colocynthis L. for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Citrullus colocynthis L. were observed. Exposure to Citrullus colocynthis L. for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed a decrease in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Citrullus colocynthis L. causes adverse effects on the reproductive system and fertility.

Juvenile Female Rats, but Not Male Rats, Show Renewal, Reinstatement, and Spontaneous Recovery Following Extinction of Conditioned Fear

ERIC Educational Resources Information Center

Park, Chun Hui J.; Ganella, Despina E.; Kim, Jee Hyun

2017-01-01

Anxiety disorders emerge early, and girls are significantly more likely to develop anxiety compared to boys. However, sex differences in fear during development are poorly understood. Therefore, we investigated juvenile male and female rats in the relapse behaviors following extinction of conditioned fear. In all experiments, 18-d-old rats first…

Spinal cord processing of cardiac nociception: are there sex differences between male and proestrous female rats?

PubMed

Little, Janine M; Qin, Chao; Farber, Jay P; Foreman, Robert D

2011-09-21

Sex differences in the characteristics of cardiac pain have been reported from clinical studies. For example, women experience chest pain less frequently than men. Women describe their chest pain as sharp and stabbing, while men have chest pain that is felt as a pressure or heaviness. Pain is also referred to the back more often in women than men. The mechanisms underlying sex differences in cardiac pain are unknown. One possible mechanism for the observed differences could be related to plasma estradiol. This study investigated the actions of estradiol on the activity of T(3) spinal neurons that process cardiosomatic information in male and female rats. Extracellular potentials of T(3) spinal neurons were recorded in response to mechanical somatic stimulation and noxious chemical cardiac stimulation in pentobarbital-anesthetized male and proestrous female rats. Fifty one percent and fifty percent of neurons responded to intrapericardial algogenic chemicals (0.2 ml) in male and female rats, respectively. Somatic fields were located by applying brush, pressure, and pinch to the upper body. Of those neurons receiving cardiac input, 54% in female and 55% in male rats also received somatic input. In both male and female rats, 81% of neurons responding to somatic stimuli had somatic fields located on the side of the upper body, while 19% of neurons had somatic fields located on the chest. These results indicate there are no significant differences in the responses of T(3) spinal neurons to cardiosomatic stimulation between male and proestrous female rats, despite differences in estradiol levels. Published by Elsevier B.V.

Lithium Visibility in Rat Brain and Muscle in Vivoby 7Li NMR Imaging

NASA Astrophysics Data System (ADS)

Komoroski, Richard A.; Pearce, John M.; Newton, Joseph E. O.

1998-07-01

The apparent concentration of lithium (Li)in vivowas determined for several regions in the brain and muscle of rats by7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determinedin vitroby high-resolution7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

Two-generation reproductive toxicity study of tributyltin chloride in female rats.

PubMed

Ogata, R; Omura, M; Shimasaki, Y; Kubo, K; Oshima, Y; Aou, S; Inoue, N

2001-05-25

A two-generation reproductive toxicity study of the effects of tributyltin chloride (TBTCl) was conducted in female rats using dietary concentrations of 5, 25, and 125 ppm TBTCl. Reproductive outcomes of dams (number and body weight of pups and the percentage of live pups) and the growth of female pups (the day of eye opening and body weight gain) were significantly decreased in the 125 ppm TBTCl group. A delay in vaginal opening and impaired estrous cyclicity were also observed in the 125 ppm TBTCl group. However, an increase in anogenital distance was found in all TBTCl groups on postnatal d 1. A dose-effect relationship was observed in TBTCl-induced changes in anogenital distance. These results indicate that the whole-life exposure to TBTCl affects the sexual development and reproductive function of female rats. In addition, the TBTCl-induced increase in anogenital distance seems to suggest it may exert a masculinizing effect on female neonates. However, the concentrations of TBTCl used in this study are not environmentally relevant.

Disposition of Phenolic and Sulfated Metabolites after Inhalation Exposure to 4-Chlorobiphenyl (PCB3) in Female Rats

PubMed Central

2015-01-01

PCBs, such as PCB3, are air contaminants in buildings and outdoors. Metabolites of PCB3 are potential endocrine disrupting chemicals and genotoxic agents. We studied the disposition of phenolic and sulfated metabolites after acute nose-only inhalation exposure to airborne PCB3 for 2 h in female rats. Inhalation exposure was carried out in three groups. In the first group, rats exposed to an estimated dose of 26 μg/rat were euthanized at 0, 1, 2, and 4 h after exposure. Highest concentrations of phenols and sulfates were observed at 0 h, and the values were 7 ± 1 and 560 ± 60 ng/mL in serum, 213 ± 120 and 842 ± 80 ng/g in liver, 31 ± 27 and 22 ± 7 ng/g in lung, and 27 ± 6 and 3 ± 0 ng/g in brain, respectively. First-order serum clearance half-lives of 0.5 h for phenols and 1 h for sulfates were estimated. In the second group, rats exposed to an estimated dose of 35 μg/rat were transferred to metabolism cages immediately after exposure for the collection of urine and feces over 24 h. Approximately 45 ± 5% of the dose was recovered from urine and consisted mostly of sulfates; the 18 ± 5% of the dose recovered from feces was exclusively phenols. Unchanged PCB3 was detected in both urine and feces but accounted for only 5 ± 3% of the dose. Peak excretion of metabolites in both urine and feces occurred within 18 h postexposure. In the third group, three bile-cannulated rats exposed to an estimated dose of 277 μg/rat were used for bile collection. Bile was collected for 4 h immediately after 2 h exposure. Biliary metabolites consisted mostly of sulfates, some glucuronides, and lower amounts of the free phenols. Control rats in each group were exposed to clean air. Clinical serum chemistry values, serum T4 level, and urinary 8-hydroxy-2′-deoxyguanosine were similar in treated and control rats. These data show that PCB3 is rapidly metabolized to phenols and conjugated to sulfates after inhalation and that both of these metabolites are distributed to liver

Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

PubMed

Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

2014-06-01

Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

PubMed

Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

2018-03-01

Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall

Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

PubMed

Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

2015-01-01

Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

Gonadal Hormone Modulation of Mu, Kappa, and Delta Opioid Antinociception in Male and Female Rats

PubMed Central

Stoffel, Erin C.; Ulibarri, Catherine M.; Folk, John E.; Rice, Kenner C.

2005-01-01

Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50°C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. In females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat. Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. PMID:15820914

Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats

PubMed Central

Intapad, Suttira; Dasinger, John Henry; Brown, Andrew D.; Fahling, Joel M.; Esters, Joyee; Alexander, Barbara T.

2015-01-01

Background The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats. Methods Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth-restricted rats at 6 and 12 months of age; sex steroids at 12 months. Results Glucose intolerance was present at 6 months of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth-restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose and testosterone at 12 months of age (P<0.05). Insulin release in response to a glucose challenge was blunted in conjunction with a reduction in protein expression of pancreatic glucose transporter type 2 and estrogen receptor alpha at 12 months of age in female growth-restricted rats (P<0.05). Conclusion This study demonstrated that slow fetal growth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift towards testosterone excess at 12 months of age in female growth-restricted rats. PMID:26854801

Photoacoustic micro-imaging of focused ultrasound induced blood-brain-barrier opening in a rat model

NASA Astrophysics Data System (ADS)

Wang, Po-Hsun; Hsu, Po-Hung; Liu, Hao-Li; Wang, Churng-Ren Chris; Li, Meng-Lin

2010-02-01

Blood brain barrier (BBB) prevents most of the drug from transmitting into the brain tissue and decreases the treatment performance for brain disease. One of the methods to overcome the difficulty of drug delivery is to locally increase the permeability of BBB with high-intensity focused ultrasound. In this study, we have investigated the feasibility of photoacoustic microscopy of focused-ultrasound induced BBB opening in a rat model in vivo with gold nanorods (AuNRs) as a contrast agent. This study takes advantage of the strong near-infrared absorption of AuNRs and their extravasation tendency from BBB opening foci due to their nano-scale size. Before the experiments, craniotomy was performed on rats to provide a path for focused ultrasound beam. Localized BBB opening at the depth of about 3 mm from left cortex of rat brains was achieved by delivering 1.5 MHz focused ultrasound energy into brain tissue in the presence of microbubbles. PEGylated AuNRs with a peak optical absorption at ~800 nm were then intravenously administered. Pre-scan prior to BBB disruption and AuNR injection was taken to mark the signal background. After injection, the distribution of AuNRs in rat brains was monitored up to 2 hours. Experimental results show that imaging AuNRs reveals BBB disruption area in left brains while there are no changes observed in the right brains. From our results, photoacoustic imaging plus AuNRs shows the promise as a novel monitoring strategy in identifying the location and variation of focused-ultrasound BBB-opening in a rat model.

Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

PubMed

Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

2018-02-01

Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

PubMed

Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

2009-12-01

The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

PubMed

Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

2015-12-01

Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain. © The Author(s) 2012.

Estrone is neuroprotective in rats after traumatic brain injury.

PubMed

Gatson, Joshua W; Liu, Ming-Mei; Abdelfattah, Kareem; Wigginton, Jane G; Smith, Scott; Wolf, Steven; Simpkins, James W; Minei, Joseph P

2012-08-10

In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (p<0.01) and neuronal injury (p<0.001), and it reduced cerebral cortical levels of TUNEL-positive staining (p<0.0001), and decreased numbers of TUNEL-positive cells in the corpus callosum (p<0.03). We assessed the levels of β-amyloid in the injured animals and found that estrone significantly decreased the cortical levels of β-amyloid after brain injury. Cortical levels of phospho-ERK1/2 were significantly (p<0.01) increased by estrone. This increase was associated with an increase in phospho-CREB levels (p<0.021), and brain-derived neurotrophic factor (BDNF) expression (p<0.0006). In conclusion, estrone given acutely after injury increases the signaling of protective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

Incubation of Methamphetamine but not Heroin Craving After Voluntary Abstinence in Male and Female Rats.

PubMed

Venniro, Marco; Zhang, Michelle; Shaham, Yavin; Caprioli, Daniele

2017-04-01

We recently introduced an animal model of incubation of methamphetamine craving after choice-based voluntary abstinence in male rats. Here we studied the generality of this phenomenon to (1) female rats, and (2) male and female rats with a history of heroin self-administration. We first trained rats to self-administer palatable food pellets for 6 days (6 h per day) for either methamphetamine (0.1 mg/kg/infusion) or heroin (0.1 mg/kg/infusion) for 12 days (6 h/day). We then assessed relapse to drug seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent either voluntary abstinence (achieved via a discrete choice procedure between drug and palatable food; 20 trials/day) or home-cage forced abstinence. We found no sex differences in methamphetamine self-administration or in the strong preference for the palatable food over methamphetamine during the choice-based voluntary abstinence. In both sexes, methamphetamine seeking in the relapse tests was higher after 21 days of either voluntary or forced abstinence than after 1 day (incubation of methamphetamine craving). We also found no sex differences in heroin self-administration or the strong preference for the palatable food over heroin during the choice-based voluntary abstinence. However, male and female rats with a history of heroin self-administration showed incubation of heroin craving after forced but not voluntary abstinence. Our results show that incubation of methamphetamine craving after voluntary abstinence generalizes to female rats. Unexpectedly, prolonged voluntary abstinence prevented the emergence of incubation of heroin craving in both sexes.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

PubMed

Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; Joseph, Vincent; Kinkead, Richard

2015-04-01

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia. Copyright © 2015 the American Physiological Society.

Looking for sexual selection in the female brain.

PubMed

Cummings, Molly E

2012-08-19

Female mate choice behaviour has significant evolutionary consequences, yet its mechanistic origins are not fully understood. Recent studies of female sensory systems have made great strides in identifying internal mechanisms governing female preferences. Only recently, however, have we begun to identify the dynamic genomic response associated with mate choice behaviour. Poeciliids provide a powerful comparative system to examine genomic responses governing mate choice and female preference behaviour, given the great range of mating systems: from female mate choice taxa with ornamental courting males to species lacking male ornamentation and exhibiting only male coercion. Furthermore, they exhibit laboratory-tractable preference responses without sexual contact that are decoupled from reproductive state, allowing investigators to isolate mechanisms in the brain without physiological confounds. Early investigations with poeciliid species (Xiphophorus nigrensis and Gambusia affinis) have identified putative candidate genes associated with female preference response and highlight a possible genomic pathway underlying female social interactions with males linked functionally with synaptic plasticity and learning processes. This network is positively correlated with female preference behaviour in the female mate choice species, but appears inhibited in the male coercive species. This behavioural genomics approach provides opportunity to elucidate the fundamental building blocks, and evolutionary dynamics, of sexual selection.

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats.

PubMed

Jayachandra Babu, R; Dayal, Pankaj Patrick; Pawar, Kasturi; Singh, Mandip

2011-11-01

Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer's and Parkinson's diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway(™). The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway(™) as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats.

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

PubMed Central

Babu, R. Jayachandra; Dayal, Pankaj Patrick; Pawar, Kasturi; Singh, Mandip

2012-01-01

Purpose Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer’s and Parkinson’s diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Methods Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway™. The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. Results MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway™ as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats. PMID:21428693

Disruption of behavior and brain metabolism in artificially reared rats.

PubMed

Aguirre-Benítez, Elsa L; Porras, Mercedes G; Parra, Leticia; González-Ríos, Jacquelina; Garduño-Torres, Dafne F; Albores-García, Damaris; Avendaño, Arturo; Ávila-Rodríguez, Miguel A; Melo, Angel I; Jiménez-Estrada, Ismael; Mendoza-Garrido, Ma Eugenia; Toriz, César; Diaz, Daniel; Ibarra-Coronado, Elizabeth; Mendoza-Ángeles, Karina; Hernández-Falcón, Jesús

2017-12-01

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[ 18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017. © 2017 Wiley Periodicals, Inc.

Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, SH.; Ballmann, C.; Quarles, C. A.

2009-03-10

The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixedmore » in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.« less

GPER modulates tone and coronary vascular reactivity in male and female rats.

PubMed

Debortoli, Angelina Rafaela; Rouver, Wender do Nascimento; Delgado, Nathalie Tristão Banhos; Mengal, Vinicius; Claudio, Erick Roberto Gonçalves; Pernomian, Laena; Bendhack, Lusiane Maria; Moysés, Margareth Ribeiro; Santos, Roger Lyrio Dos

2017-08-01

Compared with age-matched men, premenopausal women are largely protected from coronary artery disease, a difference that is lost after menopause. The effects of oestrogens are mediated by the activation of nuclear receptors (ERα and ERβ) and by the G protein-coupled oestrogen receptor (GPER). This study aims to evaluate the potential role of GPER in coronary circulation in female and male rats. The baseline coronary perfusion pressure (CPP) and the concentration-response curve with a GPER agonist (G-1) were evaluated in isolated hearts before and after the blockade of GPER. GPER, superoxide dismutase (SOD-2), catalase and gp91phox protein expression were assessed by Western blotting. Superoxide production was evaluated ' in situ ' via dihydroethidium fluorescence (DHE). GPER blockade significantly increased the CPP in both groups, demonstrating the modulation of coronary tone by GPER. G-1 causes relaxation of the coronary bed in a concentration-dependent manner and was significantly higher in female rats. No differences were detected in GPER, SOD-2 and catalase protein expression. However, gp91phox expression and DHE fluorescence were higher in male rats, indicating elevated superoxide production. Therefore, GPER plays an important role in modulating coronary tone and reactivity in female and male rats. The observed differences in vascular reactivity may be related to the higher superoxide production in male rats. These findings help to elucidate the role of GPER-modulating coronary circulation, providing new information to develop a potential therapeutic target for the treatment of coronary heart disease. © 2017 Society for Endocrinology.

Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

PubMed

Fayed, Abdel-Hasseb A; Gad, Shereen B

2011-12-01

As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

EVALUATION OF PERFLUOROOCTANE SULFONATE IN THE RAT BRAIN

EPA Science Inventory

Perfluorooctane Sulfonate (PFOS) is an environmentally persistent chemical that has been detected in humans and wildlife. PFOS is primarily distributed in liver and blood. The current study evaluated the level of PFOS in the adult and neonatal rat brain and determined whether t...

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

PubMed Central

Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

2015-01-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin’s attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin’s effect on cocaine seeking may be mediated by different mechanisms in male and females. PMID:26523890

Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

PubMed

Cao, Shenglong; Hua, Ya; Keep, Richard F; Chaudhary, Neeraj; Xi, Guohua

2018-04-01

Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits ( P <0.05). Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats. © 2018 American Heart Association, Inc.

Effect of naturally mouldy wheat or fungi administration on metallothioneins level in brain tissues of rats.

PubMed

Vasatkova, Anna; Krizova, Sarka; Krystofova, Olga; Adam, Vojtech; Zeman, Ladislav; Beklova, Miroslava; Kizek, Rene

2009-01-01

The aim of this study is to determine level of metallothioneins (MTs) in brain tissues of rats administered by feed mixtures with different content of mouldy wheat or fungi. Selected male laboratory rats of Wistar albino at age of 28 days were used in our experiments. The rats were administered by feed mixtures with different content of vitamins, naturally mouldy wheat or fungi for 28 days. At the very end of the experiment, the animals were put to death and brains were sampled. MT level was determined by differential pulse voltammetry Brdicka reaction. We found that MTs' level in brain tissues from rats administered by standard feed mixtures was significantly higher compared to the level of MTs in rats supplemented by vitamins. Further we studied the effect of supplementation of naturally mouldy wheat on MTs level in rats. In mouldy wheat we detected the presence of following fungi species: Mucor spp., Absidia spp., Penicillium spp., Aspergillus spp. and Fusarium spp. Moreover we also identified and quantified following mycotoxins - deoxynivalenol, zearalenone, T2-toxin and aflatoxins. Level of MTs determined in rats treated with 33 or 66% of mouldy wheat was significantly lower compared to control ones. On the other hand rats treated with 100% of mouldy wheat had less MTs but not significantly. Supplementation of vitamins to rats fed by mouldy wheat had adverse effect on MTs level compared to rats with no other supplementation by vitamins. Moreover vitamins supplementation has no effect on MTs level in brain tissues of rats treated or non-treated with Ganoderma lucidum L. Both mycotoxins and vitamins have considerable effect on level of MTs in brain tissues. It can be assumed that the administered substances markedly influence redox metabolism, which could negatively influence numerous biochemical pathways including those closely related with MTs.

Transgenerational effects of adolescent nicotine exposure in rats: Evidence for cognitive deficits in adult female offspring.

PubMed

Renaud, Samantha M; Fountain, Stephen B

2016-01-01

This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4days of massed training (20patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a "violation element" of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation. Copyright © 2016 Elsevier Inc. All rights

Sexual reflexes in male and female rats.

PubMed

Chung, S K; McVary, K T; McKenna, K E

1988-12-05

A novel preparation for the study of male and female sexual function in anesthetized, acutely spinalized rats is reported. In both sexes, the coitus reflex (the neuromuscular concomitants of sexual climax) could be elicited by mechanical stimulation of the distal urethra. It is concluded that the spinal sexual circuitry is essentially similar in both sexes and that the coitus reflex is generated by a hormone-insensitive spinal pattern generator and is triggered by a simple peripheral stimulus.

Fetal Cortical Transplants in Adult Rats Subjected to Experimental Brain Injury

PubMed Central

Soares, Holly; McIntosh, Tracy K.

1991-01-01

Fetal cortical tissue was injected into injured adult rat brains following concussive fluid percussion (FP) brain injury. Rats subjected to moderate FP injury received E16 cortex transplant injections into lesioned motor cortex 2 days, 1 week, 2 weeks, and 4 weeks post injury. Histological assessment of transplant survival and integration was based upon Nissl staining, glial fibrillary acidic protein (GFAP) immunocytochemistry, and staining for acetylcholinesterase. In addition to histological analysis, the ability of the transplants to attenuate neurological motor deficits associated with concussive FP brain injury was also tested. Three subgroups of rats receiving transplant 1 week, 2 weeks, and 4 weeks post injury Were chosen for evaluation of neurological motor function. Fetal cortical tissue injected into the injury site 4 weeks post injury failed to incorporate with injured host brain, did not affect glial scar formation, and exhibited extensive GFAP immunoreactivity. No improvement in neurological motor function was observed in animals receiving transplants 4 weeks post injury. Conversely, transplants injected 2 days, 1 week, or 2 weeks post injury survived, incorporated with host brain, exhibited little GFAP immunoreactivity, and successfully attenuated glial scarring. However, no significant improvement in motor function was observed at the one week or two week time points. The inability of the transplants to attenuate motor function may indicate inappropriate host/transplant interaction. Our results demonstrate that there exists a temporal window in which fetal cortical transplants can attenuate glial scarring as well as be successfully incorporated into host brains following FP injury. PMID:1782253

Transcranial MRI-guided FUS-induced BBB opening in the rat brain

NASA Astrophysics Data System (ADS)

Treat, Lisa H.; McDannold, Nathan J.; Hynynen, Kullervo

2004-05-01

The blood-brain barrier (BBB) has been a major limitation in treating diseases of the brain because therapeutic agents are either unable to penetrate or have dose-limiting side effects in diffuse opening of the BBB. A previous study demonstrated that focused ultrasound (FUS) can locally open the BBB in a rabbit model when a piece of skull is removed and that magnetic resonance imaging (MRI) can be used to guide and monitor the procedure. This study examined whether the same desired effect of local BBB disruption can be achieved by applying FUS through an intact skull in a rat model. Twenty-eight Sprague-Dawley rats were anesthetized, shaved, and sonicated at four focal locations in the brain, using a 1.5-MHz focused transducer. Contrast-enhanced MR images were obtained before and after sonication. The images indicated contrast agent penetration at the focal coordinates following Optison-enhanced sonication. This study demonstrated that the distortion of the ultrasound beam by the rat skull was not significant enough to inhibit focal BBB opening. Subsequent experiments using MRI-guided FUS to aid in targeted drug delivery to brain tumors in a rodent model could thus be performed more efficiently without cranial surgery. [Research funded by NIH Grant No. CA76550.

Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis.

PubMed

Jope, R S; Jenden, D J

1979-12-01

Specific methods utilizing combined gas chromatography mass spectrometry were used to measure the metabolism of [2H6] deanol and its effects on acetylcholine concentration in vitro and in vivo. In vitro [2H6]deanol was rapidly taken up by rat brain synaptosomes, but was neither methylated nor acetylated. [2H6]Deanol was a weak competitive inhibitor of the high affinity transport of [2H4]choline, thus reducing the synthesis of [2H4]acetylcholine. In vivo [2H6]deanol was present in the brain after i.p. or p.o. administration, but was not methylated or acetylated. Treatment of rats with [2H6]deanol significantly increased the concentration of choline in the plasma and brain but did not alter the concentration of acetylcholine in the brain. Treatment of rats with atropine (to stimulate acetylcholine turnover) or with hemicholinium-3 (to inhibit the high affinity transport of choline) did not reveal any effect of [2H6]deanol on acetylcholine synthesis in vivo. However, since [2H6]deanol did increase brain choline, it may prove therapeutically useful when the production of choline is reduced or when the utilization of choline for the synthesis of acetylcholine is impaired.

Sex differences in the outcome of juvenile social isolation on HPA axis function in rats.

PubMed

Pisu, M G; Garau, A; Boero, G; Biggio, F; Pibiri, V; Dore, R; Locci, V; Paci, E; Porcu, P; Serra, M

2016-04-21

Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot-shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine

Effects of acupuncture on tissue oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats.

PubMed

Shumake, Jason; Colorado, Rene A; Barrett, Douglas W; Gonzalez-Lima, F

2010-07-09

Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for the treatment of affective disorders. We hypothesized that fluoxetine antidepressant effects may be mediated by decreasing metabolism in the habenula and increasing metabolism in the ventral tegmental area. We measured the effects of fluoxetine on forced swim behavior and regional brain cytochrome oxidase activity in congenitally helpless rats treated for 2 weeks with fluoxetine (5mg/kg, i.p., daily). Fluoxetine reduced immobility in the forced swim test as anticipated, but congenitally helpless rats responded in an atypical manner, i.e., increasing climbing without affecting swimming. As hypothesized, fluoxetine reduced metabolism in the habenula and increased metabolism in the ventral tegmental area. In addition, fluoxetine reduced the metabolism of the hippocampal dentate gyrus and dorsomedial prefrontal cortex. This study provided the first detailed mapping of the regional brain effects of an antidepressant drug in congenitally helpless rats. All of the effects were consistent with previous studies that have metabolically mapped the effects of serotonergic antidepressants in the normal rat brain, and were in the predicted direction of metabolic normalization of the congenitally helpless rat for all affected brain regions except the prefrontal cortex. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Estrogen modulates sexually dimorphic contextual fear extinction in rats through estrogen receptor beta.

PubMed

Chang, Yao-Ju; Yang, Chih-Hao; Liang, Ying-Ching; Yeh, Che-Ming; Huang, Chiung-Chun; Hsu, Kuei-Sen

2009-11-01

Females and males are different in brain and behavior. These sex differences occur early during development due to a combination of genetic and hormonal factors and continue throughout the lifespan. Previous studies revealed that male rats exhibited significantly higher levels of contextual fear memory than female rats. However, it remains unknown whether a sex difference exists in the contextual fear extinction. To address this issue, male, normally cycling female, and ovariectomized (OVX) female Sprague-Dawley rats were subjected to contextual fear conditioning and extinction trials. Here we report that although male rats exhibited higher levels of freezing than cycling female rats after contextual fear conditioning, female rats subjected to conditioning in the proestrus and estrus stage exhibited an enhancement of fear extinction than male rats. An estrogen receptor (ER) beta agonist diarylpropionitrile but not an ERalpha agonist propyl-pyrazole-triol administration also enhanced extinction of contextual fear in OVX female rats, suggesting that estrogen-mediated facilitation of extinction involves the activation of ERbeta. Intrahippocampal injection of estradiol or diarylpropionitrile before extinction training in OVX female rats remarkably reduced the levels of freezing response during extinction trials. In addition, the locomotion or anxiety state of female rats does not vary across the ovarian cycle. These results reveal a crucial role for estrogen in mediating sexually dimorphic contextual fear extinction, and that estrogen-mediated enhancement of fear extinction involves the activation of ERbeta.

Drug- and cue-induced reinstatement of cannabinoid-seeking behaviour in male and female rats: influence of ovarian hormones

PubMed Central

Fattore, L; Spano, MS; Altea, S; Fadda, P; Fratta, W

2010-01-01

Background and purpose: Animal and human studies have shown that sex and hormones are key factors in modulating addiction. Previously, we have demonstrated that self-administration of the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN; 12.5 µg·kg−1 per infusion) is dependent on sex, intact female rats being more sensitive than males to the reinforcing properties of cannabinoids, and on the oestrous cycle, ovariectomized (OVX) females being less responsive than intact females. Experimental approach: This follow-up study investigated whether sex and ovarian function also affect reinstatement of cannabinoid-seeking in rats after exposure to drug or cue priming. Key results: After priming with 0.15 or 0.3 mg·kg−1 WIN, intact female rats exhibited stronger reinstatement than males and OVX females. Responses of intact female rats were higher than those of male and OVX rats even after priming with a drug-associated visual (Light) or auditory (Tone) cue, or a WIN + Light combination. However, latency to the first response did not differ between intact and OVX female rats, and males showed the longest latency to initiate lever-pressing activity. Conclusions and implications: Our study provides compelling evidence for a pivotal role of sex and the oestrous cycle in modulating cannabinoid-seeking, with ovariectomy diminishing drug and cue-induced reinstatement. However, it is possible that sex differences during self-administration training are responsible for sex differences in reinstatement. Finding that not only drug primings but also acute exposure to drug-associated cues can reinstate responding in rats could have significant implications for the development of pharmacological and behavioural treatments of abstinent female and male marijuana smokers. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x PMID:20590575

Two rat brain staufen isoforms differentially bind RNA.

PubMed

Monshausen, M; Putz, U; Rehbein, M; Schweizer, M; DesGroseillers, L; Kuhl, D; Richter, D; Kindler, S

2001-01-01

In neurones, a limited number of mRNAs is found in dendrites, including transcripts encoding the microtubule-associated protein 2 (MAP2). Recently, we identified a cis-acting dendritic targeting element (DTE) in MAP2 mRNAs. Here we used the yeast tri-hybrid system to identify potential trans-acting RNA-binding factors of the DTE. A cDNA clone was isolated that encodes a member of a mammalian protein family that is highly homologous to the Drosophila RNA-binding protein Staufen. Mammalian Staufen appears to be expressed in most tissues and brain areas. Two distinct rat brain Staufen isoforms, rStau+I6 and rStau-I6, are encoded by alternatively spliced mRNAs. Both isoforms contain four double-stranded RNA-binding domains (dsRBD). In the larger rStau+I6 isoform, six additional amino acids are inserted in the second dsRBD. Although both isoforms interacted with the MAP2-DTE and various additional RNA fragments in an in vitro north-western assay, rStau-I6 exhibited a stronger signal of bound radioactively labelled RNAs as compared with rStau+I6. Using an antibody directed against mammalian Staufen, the protein was detected in somata and dendrites of neurones of the adult rat hippocampus and cerebral cortex. Ultrastructural studies revealed that in dendrites, rat Staufen accumulates along microtubules. Thus in neurones, rat Staufen may serve to link RNAs to the dendritic microtubular cytoskeleton and may thereby regulate their subcellular localization.

Middle-Aged Diabetic Females and Males Present Distinct Susceptibility to Alzheimer Disease-like Pathology.

PubMed

Candeias, E; Duarte, A I; Sebastião, I; Fernandes, M A; Plácido, A I; Carvalho, C; Correia, S; Santos, R X; Seiça, R; Santos, M S; Oliveira, C R; Moreira, P I

2017-10-01

Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e.g., Alzheimer disease (AD)), the impairment of insulin signaling may be a key link. However, these may also involve changes in sex hormones' function and metabolism, ultimately contributing to the different susceptibilities between females and males to some pathologies. For example, female sex has been pointed as a risk factor for AD, particularly after menopause. However, less is known on the underlying molecular mechanisms or even if these changes start during middle-age (perimenopause). From the above, we hypothesized that sex differentially affects hormone-mediated intracellular signaling pathways in T2D brain, ultimately modulating the risk for neurodegenerative conditions. We aimed to evaluate sex-associated alterations in estrogen/insulin-like growth factor-1 (IGF-1)/insulin-related signaling, oxidative stress markers, and AD-like hallmarks in middle-aged control and T2D rat brain cortices. We used brain cortices homogenates obtained from middle-aged (8-month-old) control Wistar and non-obese, spontaneously T2D Goto-Kakizaki (GK) male and female rats. Peripheral characterization of the animal models was done by standard biochemical analyses of blood, plasma, or serum. Steroid sex hormones, oxidative stress markers, and AD-like hallmarks were given by specific ELISA kits and colorimetric techniques, whereas the levels of intracellular signaling proteins were determined by Western blotting

The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

PubMed

Maeng, Lisa Y; Shors, Tracey J

2013-01-01

Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life

Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

PubMed

Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

2014-03-01

Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

Tumorigenic effects of dichloroacetic acid in female F344 rats

EPA Science Inventory

Introduction: Dichloroacetic acid (DCA) is a halogenated organic acid produced during oxidant disinfection of drinking water. Prior studies indicate that DCA may increase liver tumors in mice. Here we evaluated the hepatic tumorigenicity of DCA in female rats when given alone ...

Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

PubMed

Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

2017-08-01

The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Variations in the neonatal environment modulate adult behavioral and brain responses to palatable food withdrawal in adult female rats.

PubMed

Colman, Juliana Barcellos; Laureano, Daniela Pereira; Reis, Tatiane Madeira; Krolow, Rachel; Dalmaz, Carla; Benetti, Carla da Silva; Silveira, Patrícia Pelufo

2015-02-01

Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure. However, the central mechanisms involved in this phenomenon are not known. Since neonatal handling has persistent effects on stress and anxiety responses, we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods. Litters were randomized into two groups: handled (H, removed from their dam for 10min per day from the first to the tenth postnatal day and placed in an incubator at 32°C) and non-handled (NH). Experiment 1: on PNDs 80-100, females were assigned to receive palatable food+rat chow for 15 or 30 days, and these two groups were compared in terms of palatable food preference, body weight and abdominal fat deposition. In Experiment 2, H and NH rats were exposed to a chronic diet of palatable food+rat chow for 15 days, followed by (a) no withdrawal, (b) 24h withdrawal from palatable food (receiving only rat chow) or (c) 7-day withdrawal from palatable food (receiving only rat chow). Body weight, 10-min rebound palatable food intake, abdominal fat deposition, serum corticosterone as well as TH and pCREB levels in the amygdala were then compared between groups. Experiment 1-chronic exposure to palatable food induces comparable metabolic effects after 15 and 30 days. Experiment 2-neonatal handling is associated with a peculiar response to palatable food withdrawal following chronic exposure for 15 days. Rats exposed to early handling ingested less of this food after a 24h withdrawal period, and displayed increased amygdala TH and pCREB levels. Variations in the neonatal environment affect both behavioral responses and amygdala neuroadaptation to acute withdrawal from a palatable diet. These findings contribute to the comprehension of the mechanisms that link early life events and altered feeding behavior and related morbidities

In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

PubMed

Boveris, A; Llesuy, S; Azzalis, L A; Giavarotti, L; Simon, K A; Junqueira, V B; Porta, E A; Videla, L A; Lissi, E A

1997-09-19

The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

PubMed Central

Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

2012-01-01

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

Soft-food diet induces oxidative stress in the rat brain.

PubMed

Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il