Rutin Treats Perimenopausal Depression Rats through Allopregnanolone Mediated mRNA Expression of Gabra4, Gabrb2 in the Prefrontal Cortex

Abstract Objective We determined whether the pathogenesis of perimenopausal depression (PMD) is associated with allopregnanolone (3α,5α-THP, ALLO) mediated GABAA receptors subunits expression changes in different brain regions. Simultaneously, we aimed to investigate the therapeutic efficacy and intervention mechanisms of the flavonoid rutin in treating PMD. Methods The PMD rat model was established by ovariectomy surgery followed by chronic unpredictable mirutin stress processes. ALLO was administered via intraperitoneal injection to increase ALLO levels in PMD rats, while rutin was administered via oral gavage for PMD treatment. Behavioral assessments, including open-fierutin test, sucrose preference test, and forced swimming test, were conducted to evaluate depressive-like behaviors in rats. ELISA was employed to measure the levels of E2, 5-HT, NE, ALLO, and GABA in the serum. Quantitative PCR was used to assess the mRNA expression of Gabra4, Gabrb2, and Gabrd in the prefrontal cortex, hippocampus, hypothalamus, and amygdala. Results The PMD rats exhibited depressive-like behavior, with decreased levels of E2, 5-HT, NE, ALLO, and GABA in the serum. The mRNA expression of Gabra4 and Gabrb2 increased in the prefrontal cortex, hippocampus, and hypothalamus of PMD rats, while Gabrd showed a increase in the hypothalamus and amygdala. ALLO improved depressive-like behavior and increased serum levels of E2, 5-HT, NE, and ALLO in PMD rats. ALLO acted on PMD rats, reduced mRNA expression of Gabra4 and Gabrb2 in the prefrontal cortex, increased mRNA expression of Gabrd in the prefrontal cortex, elevated mRNA expression of Gabra4 and Gabrd in the hippocampus, and decreased Gabrb2 mRNA expression in the hypothalamus.Rutin improved depressive-like behavior in PMD rats, increased serum levels of 5-HT and ALLO, and decreased mRNA expression of Gabra4 and Gabrb2 in the prefrontal cortex. Conclusion ALLO-mediated mRNA expression of Gabra4, Gabrb2 in the prefrontal cortex, and Gabrb2 in the hypothalamus is one of the pathological mechanisms in PMD. ALLO can improve depressive symptoms in PMD rats. Rutin (8.65 mg/kg) exerts a therapeutic effect on PMD by upregulating serum ALLO levels, subsequently downregulating mRNA expression of prefrontal cortex Gabra4 and Gabrb2.