Sex-dependent effects of acute stress and alcohol exposure during adolescence on mRNA expression of brain signaling systems involved in reward and stress responses in young adult rats.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Carlotta Gobbi, Laura Sánchez-Marín, María Flores-López, Dina Medina-Vera, Francisco Javier Pavón-Morón, Fernando Rodríguez de Fonseca, Antonia Serrano
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引用次数: 0

Abstract

Background: Adolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies.

Methods: Male and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus.

Results: The main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females.

Conclusions: This study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.

青春期急性应激和酒精暴露对年轻成年大鼠大脑奖赏和应激反应信号系统 mRNA 表达的性别依赖性影响
背景:青少年时期的压力和酗酒会增加成年后出现适应不良行为和精神障碍的风险,并具有明显的性别差异。了解这些早期事件的内在机制对于制定有针对性的预防和治疗策略至关重要:方法:雄性和雌性 Wistar 大鼠在青春期受到急性束缚应激和间歇性酒精的影响。我们评估了对血浆皮质酮(CORT)和促肾上腺皮质激素(ACTH)水平以及杏仁核和下丘脑中促肾上腺皮质激素释放激素(CRH)、神经肽 Y(NPY)、类皮质激素、阿片类和精氨酸加压素系统相关基因 mRNA 表达的持久影响:主要研究结果如下(结果:主要发现如下:(1) 血液中酒精浓度(BAC)在最后一次给药后升高,但应激男性的 BAC 水平低于非应激男性;(2) 男性体重增加明显多于女性;(3) 应激女性的促肾上腺皮质激素(ACTH)水平高于非应激女性,男性无变化;(4) 应激增加了男性的促肾上腺皮质激素(CORT)水平,而应激、酒精处理的女性的促肾上腺皮质激素(CORT)水平低于非应激女性;(5) CRH:杏仁核中女性的 Crhr1 水平较低,而酒精会降低男性的 Crhr2 水平,但不会降低女性的 Crhr2 水平。在下丘脑中发现了性别、压力和酒精之间的显著交互作用,不同性别之间有不同的模式;(6)NPY:在杏仁核中,压力降低了男性的 Npy 和 Npy1r 水平,但增加了女性的 Npy 和 Npy1r 水平。酒精会降低男性的 Npy2r 水平,但对女性的影响各不相同。在下丘脑中也观察到类似的性别特异性模式;(7)皮质类固醇系统:压力和酒精对两个脑区的 Pomc、Nr3c1 和 Nr3c2 都有复杂的性别依赖性影响;(8)阿片受体:压力和酒精削弱了男性杏仁核和女性下丘脑中 Oprm1、Oprd1 和 Oprk1 的表达;(8)血管加压素:压力和酒精对杏仁核中 Avp 和 Avpr1a 的表达有明显的交互作用,对女性的影响更大。在下丘脑中,酒精会增加女性的 Avp 水平:本研究表明,青少年急性应激反应和酒精暴露会诱导奖赏和应激反应系统发生持久的、有性别特异性的改变。这些发现强调了在预防和处理 HPA 功能障碍和精神疾病时考虑性别差异的重要性。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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