Sex Differences in Biological Processes and Nitrergic Signaling in Mouse Brain

Khaliulin, Igor; Kartawy, Maryam; Amal, Haitham

doi:10.3390/biomedicines8050124

Cited by 24 publications

(16 citation statements)

References 101 publications

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“…These results join our recent reports in showing that the mechanisms mediating extinction in adult and juvenile animals may be distinctive 6 – 8 , 29 . The present findings provide strong evidence of sex difference, even before sexual maturation, in many biological processes and signaling and point to substantial differences between males and females 76 . This will open future research directions on sex differences in neurological and psychiatric disorders 76 , 77 .…”

Section: Discussionsupporting

confidence: 55%

Sex-dimorphic role of prefrontal oxytocin receptors in social-induced facilitation of extinction in juvenile rats

et al. 2020

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We previously reported that in the adult animal extinction in pairs resulted in enhanced extinction, showing that social presence can reduce previously acquired fear responses. Based on our findings that juvenile and adult animals differ in the mechanisms of extinction, here we address whether the social presence of a conspecific affects extinction in juvenile animals similarly to adults. We further address whether such presence has a different impact on juvenile males and females. To that end, we examined in our established experimental setting whether conditioned male and female animals extinguish contextual fear memory better while in pairs. Taking advantage of the role of oxytocin (OT) in the mediation of extinction memory and social interaction, we also study the effect of antagonizing the OT receptors (OTR) either systemically or in the prefrontal cortex on social interaction-induced effects of fear extinction. The results show that social presence accelerates extinction in males and females as compared to the single condition. Yet, we show differential and opposing effects of an OTR antagonist in both sexes. Whereas in females, the systemic application of an OTR antagonist is associated with impaired extinction, it is associated with enhanced extinction in males. In contrast, prefrontal OT is not engaged in extinction in juvenile males, while is it is critical in females. Previously reported differences in the levels of prefrontal OT between males and females might explain the differences in OT action. These results suggest that even during the juvenile period, critical mechanisms are differently involved in the regulation of fear in males and females.

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Section: Discussionsupporting

confidence: 55%

Sex-dimorphic role of prefrontal oxytocin receptors in social-induced facilitation of extinction in juvenile rats

et al. 2020

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“…Between our study and that of Sowers et al (2019), which was also conducted in C57BL/6J mice but in hippocampi, there were several proteins that were differentially regulated in the same direction by sex (Alb, Camk2a, Cpne6, and Synpr) and some proteins that were differentially regulated but in opposite directions (Anxa6, L1cam, Scg2, and Vat1l). Other studies examining sex differences in experimentally naïve rodents (i.e., under "baseline" conditions), focused on specific neuronal compartments such as the synapse (Distler et al, 2020), microglia (Guneykaya et al, 2018), mitochondria in microvasculature (Cikic et al, 2021), or a specific type of protein modification (Khaliulin et al, 2020). Thus, the current study demonstrating a significant degree of sex difference in the mesolimbic proteome at baseline is an important contribution to broadening the understanding of baseline sex differences in the mouse brain.…”

Section: Discussionmentioning

confidence: 79%

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

Lee

Mansuri²,

Wilson³

et al. 2021

Front. Mol. Neurosci.

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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.

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“…One important aspect of the research on brain sexual di-morphism was finding the changes in S-nitrosylation (S-NO) of mouse cortical proteins. Mass spectrometry analysis revealed that female mice showed elevated levels of S-NO proteins involved in synaptic processes, while males exhibited higher enrichment of the S-NO-dependent cytoskeletal pathways [50]. S-NO is engaged in a variety of cellular processes and, importantly, this PTM appears to compete with S-PALM for cysteine residues in proteins [51,52].…”

Section: Discussionmentioning

confidence: 98%

S-Palmitoylation of Synaptic Proteins as a Novel Mechanism Underlying Sex-Dependent Differences in Neuronal Plasticity

Zaręba-Kozioł

Bartkowiak-Kaczmarek

Roszkowska

et al. 2021

IJMS

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Although sex differences in the brain are prevalent, the knowledge about mechanisms underlying sex-related effects on normal and pathological brain functioning is rather poor. It is known that female and male brains differ in size and connectivity. Moreover, those differences are related to neuronal morphology, synaptic plasticity, and molecular signaling pathways. Among different processes assuring proper synapse functions are posttranslational modifications, and among them, S-palmitoylation (S-PALM) emerges as a crucial mechanism regulating synaptic integrity. Protein S-PALM is governed by a family of palmitoyl acyltransferases, also known as DHHC proteins. Here we focused on the sex-related functional importance of DHHC7 acyltransferase because of its S-PALM action over different synaptic proteins as well as sex steroid receptors. Using the mass spectrometry-based PANIMoni method, we identified sex-dependent differences in the S-PALM of synaptic proteins potentially involved in the regulation of membrane excitability and synaptic transmission as well as in the signaling of proteins involved in the structural plasticity of dendritic spines. To determine a mechanistic source for obtained sex-dependent changes in protein S-PALM, we analyzed synaptoneurosomes isolated from DHHC7-/- (DHHC7KO) female and male mice. Our data showed sex-dependent action of DHHC7 acyltransferase. Furthermore, we revealed that different S-PALM proteins control the same biological processes in male and female synapses.

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Sex Differences in Biological Processes and Nitrergic Signaling in Mouse Brain

Cited by 24 publications

References 101 publications

Sex-dimorphic role of prefrontal oxytocin receptors in social-induced facilitation of extinction in juvenile rats

Sex-dimorphic role of prefrontal oxytocin receptors in social-induced facilitation of extinction in juvenile rats

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

S-Palmitoylation of Synaptic Proteins as a Novel Mechanism Underlying Sex-Dependent Differences in Neuronal Plasticity

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