scholarly journals SEX DIFFERENCES IN μ-OPIOID REGULATION OF COERULEAR-CORTICAL TRANSMISSION

2020 ◽  
Author(s):  
Herminio M Guajardo ◽  
Rita J Valentino
Keyword(s):  
Sex Differences ◽  
Prefrontal Cortex ◽  
Cognitive Flexibility ◽  
Field Potential ◽  
Endogenous Opioids ◽  
Female Rats ◽  
Cognitive Responses ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACTStress-induced activation of locus coeruleus (LC)-norepinephrine (NE) projections to the prefrontal cortex is thought to promote cognitive responses to stressors. LC activation by stressors is modulated by endogenous opioids that serve to restrain LC activation and to facilitate a return to baseline activity upon stress termination. Sex differences in this opioid influence could be a basis for sex differences in stress vulnerability. Consistent with this, we recently demonstrated that μ-opioid receptor (MOR) expression is decreased in the female rat LC compared to the male LC and this was associated with sexually distinct consequences of activating MOR in the LC on cognitive flexibility. Given that the LC-NE system affects cognitive flexibility through its projections to the medial prefrontal cortex (mPFC), the present study quantified and compared the effects of LC-MOR activation on mPFC neural activity in male and female rats. Local field potential (LFPs) were recorded from the mPFC of freely behaving male and female rats before and following local LC microinjection of the MOR agonist, DAMGO or vehicle. Intra-LC DAMGO altered the LFP power spectrum selectively in male, but not female rats, resulting in a time-dependent increase in the power in delta and alpha frequency bands. LC microinfusion of ACSF had no effect in either sex. Together, the results are consistent with previous evidence for decreased MOR function in the female rat LC and demonstrate that this translates to a diminished effect on cortical activity that can account for sex differences in cognitive consequences. Decreased LC-MOR function in females could contribute to greater stress-induced activation of the LC, and increased vulnerability of females to hyperarousal symptoms of stress-related neuropsychiatric pathologies.

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS:

1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson
Keyword(s):  
Ascorbic Acid ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Female Rat ◽  
Feedback Effects ◽  
Male And Female ◽  
Prostate Weight ◽  
Male And Female Rats ◽  
Males And Females ◽  
Normal Males

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

scholarly journals Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Rat Kidney ◽  
Female Rats ◽  
Amide Bond ◽  
Male Rats ◽  
Dark Agouti ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver And Kidney

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity

scholarly journals Intrasplenic Transplantation of Isolated Adult Rat Hepatocytes

2011 ◽  
Vol 40 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Meena R. Sharma ◽  
Wojciech Dworakowski ◽  
Bernard H. Shapiro
Keyword(s):  
Cytochrome P450 ◽  
Adult Male ◽  
Total Concentration ◽  
Rat Hepatocytes ◽  
Female Rats ◽  
Female Rat ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Male And Female Rats ◽  
Male Specific

Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2—which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450—were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host’s liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation.

P3512Sex differences in rats with heart failure with preserved ejection fraction and the effect of autonomic modulation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stavrakis ◽  
K Elkholey ◽  
L Morris ◽  
Y Li ◽  
S S Po
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Female Rats ◽  
Autonomic Modulation ◽  
Preserved Ejection Fraction ◽  
Qtc Prolongation ◽  
Male And Female ◽  
Male And Female Rats

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF and sudden death is the leading cause of mortality. There are considerable sex differences in cardiac structure and function, which may be related to outcomes in HFpEF. Transcutaneous vagus nerve stimulation (tVNS) is antiarrhythmic. Purpose To describe sex differences in mortality, autonomic tone and ECG parameters in rats with HFpEF and examine the effect of tVNS on these outcomes. Methods Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of LS or HS diets, HS rats were randomized to receive active or sham tVNS, 30min daily (20Hz, 3mA) for 4 weeks. The rats were monitored daily for 4 weeks for the development of HFpEF. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint). Heart rate variability (HRV) was calculated at the respective time points. ECG and HRV parameters were analyzed in a blinded fashion. Logistic regression analysis was performed to identify independent predictors of mortality. Results A total of 58 rats were included (5 male LS, 6 female LS, 22 male HS and 25 female HS). HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There were 4 sudden cardiac deaths in males (with ventricular tachycardia documented in 1 rat), whereas all the females died of HF or stroke. Corrected QT (QTc) at baseline significantly prolonged in HS compared to LS rats (250.5±14.4ms vs. 226.8±13.9ms, respectively, p=0.0007), while all other ECG parameters did not differ significantly between groups. In HS rats, QTc prolongation was significantly more pronounced in males compared to females (259.4±20.6ms vs. 243.8±14.5ms, respectively, P=0.002). In univariate analysis, prolonged baseline QTc (OR=1.04; 95% CI 1.01–1.06, p=0.003) and male sex (OR=3.21, 95% CI 1.19–8.66, p=0.016) predicted mortality. However, in multivariate analysis, QTc was the only significant predictor of mortality (OR=1.04; 95% CI 1.01–1.06, p=0.003). After 4 weeks of treatment, active tVNS significantly decreased QTc compared to sham (244.6±13.8ms vs. 255.8±14.0ms, respectively, p=0.017) in both male and female rats in a similar manner. The low frequency to high frequency ratio (LF/HF) of HRV, which reflects sympathovagal balance, was significantly decreased in active tVNS rats compared to sham (0.21±0.13 vs. 0.54±0.14, respectively; p=0.001) in both male and female rats in a similar manner. Conclusions Male rats with HFpEF exhibit worse survival compared to females and are at higher risk for sudden death. QTc prolongation accounts for the increased risk of sudden death in males compared to females. Autonomic modulation with tVNS attenuates the unfavorable changes in QTc and HRV induced by HS diet and may be used to prevent ventricular arrhythmias in patients with HFpEF.

Effect of long-term undernutrition on male and female rat diaphragm contractility, fatigue, and fiber types

1994 ◽  
Vol 76 (4) ◽  
pp. 1540-1547 ◽  
Author(s):  
D. J. Prezant ◽  
B. Richner ◽  
T. K. Aldrich ◽  
D. E. Valentine ◽  
E. I. Gentry ◽  
...  
Keyword(s):  
Weight Gain ◽  
Fatigue Resistance ◽  
Female Rats ◽  
Fiber Types ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Males And Females ◽  
Diaphragm Atrophy

The effects of long-term undernutrition (10 wk) on diaphragm contractility, fatigue, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by using direct stimulation at 37 degrees C. Undernutrition allowed for continued growth in males and females but with substantial reductions in weight gain. Relative to control rats of the same sex, final weights were significantly lower in undernourished males (74 +/- 3%) than females (90 +/- 5%), but weight gain was not significantly different between undernourished males (58 +/- 5%) and females (60 +/- 3%). Only in males did undernutrition significantly reduce costal diaphragm weight (to 77 +/- 5% of control). Diaphragm forces, normalized for cross-sectional area, were not significantly different from male or female control values. Fatigue resistance indexes (fatigue/baseline force) were increased at all stimulation frequencies in undernourished males but not in undernourished females. Costal diaphragm atrophy, involving types I and II fibers, occurred in undernourished males but not in undernourished females. In conclusion, despite long-term undernutrition reducing weight gain to similar levels in males and females (relative to control), there was excellent preservation of diaphragm weight, function, and structure in females but, although diaphragm atrophy occurred, there was preserved contractility and increased fatigue resistance in males.

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