Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis

Tatyana Strekalova, Oleg Moskvin, Aayushi Y. Jain, Nikita Gorbunov, Anna Gorlova, Daria Sadovnik, Aleksei Umriukhin, Raymond Cespuglio, Wing Shan Yu, Anna Chung Kwan Tse, Allan V. Kalueff, Klaus Peter Lesch*, Lee Wei Lim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Aggression is a complex social behavior, critically involving brain serotonin (5-HT) function. The neurobiology of female aggression remains elusive, while the incidence of its manifestations has been increasing. Yet, animal models of female aggression are scarce. We previously proposed a paradigm of female aggression in the context of gene x environment interaction where mice with partial genetic inactivation of tryptophan hydroxylase-2 (Tph2 +/− mice), a key enzyme of neuronal 5-HT synthesis, are subjected to predation stress resulting in pathological aggression. Using deep sequencing and the EBSeq method, we studied the transcriptomic signature of excessive aggression in the prefrontal cortex of female Tph2 +/− mice subjected to rat exposure stress and food deprivation. Challenged mutants, but not other groups, displayed marked aggressive behaviors. We found 26 genes with altered expression in the opposite direction between stressed groups of both Tph2 genotypes. We identified several molecular markers, including Dgkh, Arfgef3, Kcnh7, Grin2a, Tenm1 and Epha6, implicated in neurodevelopmental deficits and psychiatric conditions featuring impaired cognition and emotional dysregulation. Moreover, while 17 regulons, including several relevant to neural plasticity and function, were significantly altered in stressed mutants, no alteration in regulons was detected in stressed wildtype mice. An interplay of the uncovered pathways likely mediates partial Tph2 inactivation in interaction with severe stress experience, thus resulting in excessive female aggression.

Original languageEnglish
Pages (from-to)1113-1132
Number of pages20
JournalJournal of Neural Transmission
Volume130
Issue number9
DOIs
Publication statusPublished - Sept 2023
Externally publishedYes

Keywords

  • Aggression
  • Deep sequencing (mRNAseq)
  • Mice
  • Predation stress
  • Prefrontal cortex
  • Serotonin
  • Tryptophan hydroxylase-2 (Tph2)

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