scholarly journals Sex Differences in the Ventral Tegmental Area and Nucleus Accumbens Proteome at Baseline and Following Nicotine Exposure

2021 ◽  
Vol 14 ◽  
Author(s):  
Angela M. Lee ◽  
Mohammad Shahid Mansuri ◽  
Rashaun S. Wilson ◽  
TuKiet T. Lam ◽  
Angus C. Nairn ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Signaling Pathways ◽  
Nicotine Addiction ◽  
Nicotine Exposure ◽  
Male And Female ◽  
Female Mice ◽  
Chronic Nicotine ◽  
Nicotine Administration

Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging, and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. In C3H/HeJ mice, similar numbers of proteins were differentially regulated between sexes at baseline compared with within each sex after sub-chronic nicotine administration. In C57BL/6J mice, there were significantly greater numbers of proteins differentially regulated between sexes at baseline compared with within each sex after chronic nicotine administration and withdrawal. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.

scholarly journals VTA MC3R neurons control feeding in an activity and sex-dependent manner in mice

2021 ◽  
Author(s):  
Anna I. Dunigan ◽  
David P. Olson ◽  
Aaron G. Roseberry
Keyword(s):  
Body Weight ◽  
Sex Differences ◽  
Tyrosine Hydroxylase ◽  
Food Intake ◽  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
Dependent Manner ◽  
Male And Female ◽  
Female Mice

AbstractIncreasing evidence indicates that the melanocortin and mesolimbic dopamine systems interact to regulate feeding and body weight. Because melanocortin-3 receptors (MC3R) are highly expressed in the ventral tegmental area (VTA), we tested whether VTA neurons expressing these receptors (VTA MC3R neurons) control feeding and body weight in vivo. We also tested whether there were sex differences in the ability of VTA MC3R neurons to control feeding, as MC3R −/− mice show sex-dependent alterations in reward feeding and dopamine levels, and there are clear sex differences in multiple dopamine-dependent behaviors and disorders. DREADD receptors were used to acutely activate and inhibit VTA MC3R neurons and changes in food intake and body weight were measured. Acutely altering the activity of VTA MC3R neurons decreased feeding in an activity- and sex-dependent manner, with acute activation decreasing feeding, but only in females, and acute inhibition decreasing feeding, but only in males. These differences did not appear to be due to sex differences in the number of VTA MC3R neurons, the ability of hM3Dq to activate VTA MC3R neurons, or the proportion of VTA MC3R neurons expressing tyrosine hydroxylase (TH). These studies demonstrate an important role for VTA MC3R neurons in the control of feeding and reveal important sex differences in behavior, whereby opposing changes in neuronal activity in male and female mice cause similar changes in behavior.

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 Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice

2008 ◽  
Vol 439 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Barbara J. Caldarone ◽  
Sarah L. King ◽  
Marina R. Picciotto
Keyword(s):  
Sex Differences ◽  
Locomotor Activity ◽  
Nicotine Exposure ◽  
Chronic Nicotine

scholarly journals Androgen sulphate formation in male and female mice

1969 ◽  
Vol 115 (3) ◽  
pp. 489-493
Author(s):  
D A Lewis
Keyword(s):  
Sex Differences ◽  
Sulphuric Acid ◽  
Female Rats ◽  
Dehydroepiandrosterone Sulphate ◽  
Male And Female ◽  
Female Mice ◽  
Liver Slices ◽  
Rats And Mice

1. After the administration of large doses of androsterone, epiandrosterone, dehydroepiandrosterone and testosterone to mice, females excreted more of the dose conjugated with sulphuric acid than did males. 2. Liver slices from female mice conjugated androgens with sulphuric acid to a greater extent than did slices from males. 3. Sulphotransferase preparations from livers of female rats and mice catalysed the formation of dehydroepiandrosterone sulphate at a faster rate than preparations from livers of the male animals. 4. A possible explanation for the observed sex differences is discussed.

Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice

2021 ◽  
Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Frailty Index ◽  
Mesenteric Arteries ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Age Related

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

Abstract T P210: Splenectomy Attenuates Sex Differences in Infarct Volume Following Experimental Stroke in Mice

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Jianming Wang ◽  
Sheetal Bodhankar ◽  
Halina Offner ◽  
Stephanie J Murphy
Keyword(s):  
Sex Differences ◽  
Blood Glucose ◽  
Brain Injury ◽  
Infarct Volume ◽  
Blood Gases ◽  
Experimental Stroke ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Male And Female ◽  
Female Mice

It is now increasingly clear that human stroke can have other serious consequences besides brain damage that can impact on patient survival and recovery. For example, many stroke patients succumb to CNS injury-induced immunodepression and fatal infections. Our prior work suggests that evolving cerebral ischemic injury elicits a cycle of injury from brain-to-spleen-to-brain that is strongly influenced by sex. We determined if splenic immunocytes are important in contributing to sex differences in post-ischemic brain injury. Male and female C57BL/6J mice were splenectomized 14 days before experimental stroke. Male and female mice with or without splenectomy (n=9-10 per group) then underwent 60 min of middle cerebral artery occlusion (MCAO) via intraluminal filament. Laser-Doppler flowmetry (LDF) was used to monitor cortical perfusion. All mice were euthanized and brains collected at 96 hours of reperfusion. Infarct volume (% corrected contralateral structure) was determined by image analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. Mean arterial blood pressure (MABP), blood gases (pH, P a O 2 , P a CO 2 ), and blood glucose were measured at 30 min MCAO and at 15 min of reperfusion in separate groups of male and female mice with or without splenectomy (n=5 per group). Relative LDF changes (% baseline), MABP, blood gases, and blood glucose during and after MCAO were comparable among the experimental groups. We observed that infarct volume in females (cortex, 41±4%; striatum, 55±6%) was smaller ( P <0.05) compared to males (cortex, 52±3%; striatum, 75±3%) at 96 hours of reperfusion. However, no differences (cortex, P =0.313; striatum, P =0.601) in infarct volume were seen between splenectomized male (cortex, 43±4%; striatum, 51±7%) and female (cortex, 38±4%; striatum, 46±5%) mice. Our data suggest that removal of all splenocyte lineages via splenectomy attenuates sex differences in post-ischemic brain injury. Future studies will evaluate the role of different splenic immunocyte subsets, such as T or B lymphocytes, on male vs. female ischemic brain outcomes. This study was supported by National Institutes of Health grant NS076013.

scholarly journals Sex differences in renal and metabolic responses to a high-fructose diet in mice

2015 ◽  
Vol 308 (5) ◽  
pp. F400-F410 ◽  
Author(s):  
Nikhil Sharma ◽  
Lijun Li ◽  
C. M. Ecelbarger
Keyword(s):  
Sex Differences ◽  
Glucose Transporter ◽  
Collecting Duct ◽  
Urine Volume ◽  
Thick Ascending Limb ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
High Fructose Diet ◽  
High Fructose

High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice ( n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K+ and decreased plasma Na+ with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na+-K+-2Cl− cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption.

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