An epigenomic shift in amygdala marks the transition from pup-aversive to maternal-like behaviors in alloparenting virgin female mice

In many species, adults will care for young offspring that are not their own, a phenomenon called alloparenting. However, most nonparental adults experience an initial aversion to newborns, which must be overcome before a robust display of parental-like behaviors can begin. To capture neurogenomic events underlying this dramatic behavioral transition, we analyzed brain gene expression and chromatin profiles of virgin female mice co-housed with mothers during pregnancy and after birth. After an initial display of agonistic behaviors and a surge of defense-related gene expression, we observed a dramatic shift in the chromatin landscape specifically in amygdala, accompanied by a dampening of the defense-related genes. This shift coincided with the emergence of behaviors and gene expression classically associated with maternal care. The results reveal the outlines of a neurogenomic program associated with this dramatic aversive-to-affiliative behavioral switch, and suggest molecular networks that may be relevant to human postpartum mental health.

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Histone Deacetylase Inhibition Induces Long-Lasting Changes in Maternal Behavior and Gene Expression in Female Mice

Endocrinology ◽

10.1210/en.2013-1946 ◽

2014 ◽

Vol 155 (9) ◽

pp. 3674-3683 ◽

Cited By ~ 28

Author(s):

Danielle S. Stolzenberg ◽

Jacqueline S. Stevens ◽

Emilie F. Rissman

Keyword(s):

Gene Expression ◽

Histone Deacetylase ◽

Maternal Behavior ◽

Dna Methyltransferase ◽

Virgin Female ◽

Maternal Responsiveness ◽

Gene Promoters ◽

Female Mice ◽

Maternal Experience ◽

Hdaci Treatment

Abstract In many species, including mice, maternal responsiveness is experience-dependent and permanent, lasting for long periods (months to years). We have shown that after brief exposures to pups, virgin female mice continue to respond maternally toward pups for at least one month. Administration of a histone deacetylase inhibitor (HDACi) reduces the amount of maternal experience required to affect maternal behavior and gene expression. In this set of studies, we examined the epigenetic mechanisms that underlie these motivated behaviors. We assessed whether the effects of HDACi persisted 1 month after the initial experience (in the absence of continued pup experience or HDACi treatment) and whether the maintenance of maternal memory was associated with stable changes in gene expression. Using chromatin immunoprecipitation, we examined whether Esr2 and Oxt gene expression might be mediated by recruitment of the histone acetyltransferase cAMP response element binding protein (CBP) to their promoter regions after maternal memory consolidation. We report that HDACi treatment induced long-lasting changes in maternal responsiveness. Maternal learning was associated with increased recruitment of CBP to the Esr2 and Oxt gene promoters during the consolidation of maternal memory as well as a persistent increase in estrogen receptor-β (Esr2) mRNA and decreased expression of the de novo DNA methyltransferase Dnmt3a within the medial preoptic area. The consolidation of the maternal experience may involve the CBP recruitment and stable changes in gene expression, which maintain increased maternal responsiveness for long periods of time.

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Social hierarchy position in female mice is associated with plasma corticosterone levels and hypothalamic gene expression

10.1101/529131 ◽

2019 ◽

Author(s):

Cait M. Williamson ◽

Won Lee ◽

Alexandra R. Decasien ◽

Alesi Lanham ◽

Russell D. Romeo ◽

...

Keyword(s):

Gene Expression ◽

Social Relationships ◽

Virgin Female ◽

Physical Space ◽

Ventromedial Hypothalamus ◽

Plasma Corticosterone ◽

Social Hierarchies ◽

Female Mice ◽

Linear Hierarchies ◽

Estradiol Levels

AbstractSocial hierarchies emerge when animals compete for access to resources such as food, mates or physical space. Wild and laboratory male mice have been shown to develop linear hierarchies, however, less is known regarding whether female mice have sufficient intrasexual competition to establish significant social dominance relationships. In this study, we examined whether groups of outbred CD-1 virgin female mice housed in a large vivaria formed social hierarchies. We show that females use fighting, chasing and mounting behaviors to rapidly establish highly directionally consistent social relationships. Notably, these female hierarchies are less linear, steep and despotic compared to male hierarchies. Female estrus state was not found to have a significant effect on aggressive behavior, though dominant females had elongated estrus cycles (due to increased time in estrus) compared to subordinate females. Plasma estradiol levels were equivalent between dominant and subordinate females. Subordinate females had significantly lower levels of basal corticosterone compared to dominant females. Analyses of gene expression in the ventromedial hypothalamus indicated that subordinate females have elevated ERα, ERβ and OTR mRNA compared to dominant females. This study provides a methodological framework for the study of the neuroendocrine basis of female social aggression and dominance in laboratory mice.

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Faculty Opinions recommendation of Differences in inhibitory avoidance, cortisol and brain gene expression in TL and AB zebrafish.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725449294.793510550 ◽

2015 ◽

Author(s):

Judith S Eisen

Keyword(s):

Gene Expression ◽

Inhibitory Avoidance ◽

Brain Gene Expression

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Faculty Opinions recommendation of Endometriosis alters brain electro-physiology, gene expression and increased pain sensitization, anxiety, and depression in female mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732633741.793546500 ◽

2018 ◽

Author(s):

Daniel Vaiman

Keyword(s):

Gene Expression ◽

Anxiety And Depression ◽

Female Mice ◽

Pain Sensitization

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Effect of combination of peripheral oxytocin and naltrexone at subthreshold doses on food intake, body weight and feeding-related brain gene expression in male rats

Physiology & Behavior ◽

10.1016/j.physbeh.2021.113464 ◽

2021 ◽

pp. 113464

Author(s):

Mitchell A. Head ◽

Allen S. Levine ◽

David G. Christian ◽

Anica Klockars ◽

Pawel K. Olszewski

Keyword(s):

Gene Expression ◽

Body Weight ◽

Food Intake ◽

Male Rats ◽

Brain Gene Expression

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Competing Endogenous RNAs in Cervical Carcinogenesis: A New Layer of Complexity

Processes ◽

10.3390/pr9060991 ◽

2021 ◽

Vol 9 (6) ◽

pp. 991

Author(s):

Fernanda Costa Brandão Berti ◽

Sara Cristina Lobo-Alves ◽

Camila de Freitas Oliveira-Toré ◽

Amanda Salviano-Silva ◽

Karen Brajão de Oliveira ◽

...

Keyword(s):

Gene Expression ◽

Fine Tuning ◽

Molecular Networks ◽

Cervical Carcinogenesis ◽

Molecular Changes ◽

Cellular Processes ◽

Target Mrnas ◽

Competing Endogenous Rnas ◽

Cervical Cells ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs) regulate gene expression by binding to complementary sequences within target mRNAs. Apart from working ‘solo’, miRNAs may interact in important molecular networks such as competing endogenous RNA (ceRNA) axes. By competing for a limited pool of miRNAs, transcripts such as long noncoding RNAs (lncRNAs) and mRNAs can regulate each other, fine-tuning gene expression. Several ceRNA networks led by different lncRNAs—described here as lncRNA-mediated ceRNAs—seem to play essential roles in cervical cancer (CC). By conducting an extensive search, we summarized networks involved in CC, highlighting the major impacts of such dynamic molecular changes over multiple cellular processes. Through the sponging of distinct miRNAs, some lncRNAs as HOTAIR, MALAT1, NEAT1, OIP5-AS1, and XIST trigger crucial molecular changes, ultimately increasing cell proliferation, migration, invasion, and inhibiting apoptosis. Likewise, several lncRNAs seem to be a sponge for important tumor-suppressive miRNAs (as miR-140-5p, miR-143-3p, miR-148a-3p, and miR-206), impairing such molecules from exerting a negative post-transcriptional regulation over target mRNAs. Curiously, some of the involved mRNAs code for important proteins such as PTEN, ROCK1, and MAPK1, known to modulate cell growth, proliferation, apoptosis, and adhesion in CC. Overall, we highlight important lncRNA-mediated functional interactions occurring in cervical cells and their closely related impact on cervical carcinogenesis.

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