Antidepressant effects of activation of infralimbic cortex via upregulation of BDNF and β-catenin in an estradiol withdrawal model

Jiali Chen; Yiying Zhou; Miaojun Lai; Yanping Zhang; Yifang Hu; Dingding Zhuang; Wenhua Zhou; Yisheng Zhang

doi:10.1007/s00213-024-06610-z

Antidepressant effects of activation of infralimbic cortex via upregulation of BDNF and β-catenin in an estradiol withdrawal model

Psychopharmacology (Berl). 2024 May 14. doi: 10.1007/s00213-024-06610-z. Online ahead of print.

Authors

Jiali Chen^#¹, Yiying Zhou^#², Miaojun Lai^#^{2

3}, Yanping Zhang¹, Yifang Hu¹, Dingding Zhuang², Wenhua Zhou^{4

5}, Yisheng Zhang⁶

Affiliations

¹ Department of Obstetrics, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315040, P. R. China.
² Zhejiang Provincial Key Lab of Addiction Research, The Affiliated Kangning Hospital of Ningbo University, Ningbo, 315201, P. R. China.
³ Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, 315201, P. R. China.
⁴ Zhejiang Provincial Key Lab of Addiction Research, The Affiliated Kangning Hospital of Ningbo University, Ningbo, 315201, P. R. China. whzhou@vip.163.com.
⁵ Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, 315201, P. R. China. whzhou@vip.163.com.
⁶ Department of Obstetrics, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315040, P. R. China. doctorzhangys@139.com.

^# Contributed equally.

PMID: 38743109
DOI: 10.1007/s00213-024-06610-z

Abstract

Rationale: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear.

Objectives: This study was to observe the antidepressant effect and expression of BDNF and β-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD.

Methods: Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of β-catenin and BDNF were observed by western blotting.

Results: Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or β-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and β-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats.

Conclusions: Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and β-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD.

Keywords: Brain-derived neurotrophic factor; Glutamate; Infralimbic cortex; Postpartum depression; γ-aminobutyric acid receptor.

Abstract

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