Sex-specific effects of chronic fluoxetine on c-Fos expression in Murine brain regions

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-05-24 DOI:10.1016/j.brainres.2025.149735

Minerva Ortiz-Valladares , Christian Peregrino-Ramírez , Ricardo Pedraza-Medina , Jorge Guzmán-Muñiz , Oscar Gonzalez-Perez

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Abstract

Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widely prescribed for treating mood disorders. Despite its therapeutic benefits, the precise mechanisms and brain regions impacted by long-term FLX treatment remain understood. To explore this, we analyzed c-Fos immunoreactivity in brain regions associated with emotional regulation after 30-day oral FLX treatment in male and female mice. Our findings showed a significant reduction in c-Fos expression in FLX-treated groups compared to controls, suggesting decreased cellular activity in several brain regions. Furthermore, significant sex differences were observed as male mice exhibited higher c-Fos activity than females. Treatment interaction indicated FLX might reduce these sex disparities, except in the CA2 region of the hippocampus, where males maintained higher activity. Notably, FLX appeared to minimize the sex-based disparities in c-Fos expression in several regions, suggesting that FLX equalizes cellular activity across sexes in areas associated with cognitive and emotional functions. Altogether, these data indicate that FLX modulates cellular activity via a sex-dependent mechanism, which highlights the relevance of considering sex differences in the assessment of the neurobiological effects of FLX.

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慢性氟西汀对小鼠脑区c-Fos表达的性别特异性影响

氟西汀（FLX）是一种选择性血清素再摄取抑制剂，被广泛用于治疗情绪障碍。尽管具有治疗效果，但长期FLX治疗的确切机制和脑区影响仍不清楚。为了探讨这一点，我们分析了雄性和雌性小鼠口服FLX 30天后大脑中与情绪调节相关区域的c-Fos免疫反应性。我们的研究结果显示，与对照组相比，flx治疗组的c-Fos表达显著降低，表明大脑几个区域的细胞活性降低。此外，雄性小鼠比雌性小鼠表现出更高的c-Fos活性，性别差异显著。治疗相互作用表明，FLX可能会减少这些性别差异，除了海马的CA2区域，在那里男性保持较高的活性。值得注意的是，FLX似乎最小化了几个区域c-Fos表达的性别差异，这表明FLX在与认知和情感功能相关的区域平衡了性别间的细胞活动。总之，这些数据表明FLX通过性别依赖机制调节细胞活动，这突出了在评估FLX的神经生物学效应时考虑性别差异的相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.