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慢性依地普仑治疗不会改变新生期应激对雄性和雌性青春期大鼠海马 BDNF 水平、5-HT 表达和情绪行为的影响。

Chronic Escitalopram Treatment Does Not Alter the Effects of Neonatal Stress on Hippocampal BDNF Levels, 5-HT Expression and Emotional Behaviour of Male and Female Adolescent Rats.

机构信息

Departamento de Psicobiologia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, 1° andar, São Paulo, SP, 04024-002, Brazil.

出版信息

Mol Neurobiol. 2021 Mar;58(3):926-943. doi: 10.1007/s12035-020-02164-1. Epub 2020 Oct 15.

Abstract

Early life stress is considered a risk factor for the development of long-term psychiatric disorders. Maternal deprivation (MD) is a useful paradigm to understand the neurobiological underpinnings of early stress-induced changes in neurodevelopment trajectory. The goal of the present study was to examine the effects of a chronic treatment with escitalopram (ESC) on the hippocampal levels of BDNF and neuropeptide Y (NPY), expression of serotonin type 1A receptor (5-HT), plasma corticosterone levels and emotional behaviours in male and female adolescent rats submitted to MD at 9 days of life (group DEP9) and challenged with a brief and mild stress (saline injection (SAL)) at the end of MD. Whole litters were kept with mothers (CTL) or submitted to MD (DEP9). Within each group, pups were stress-challenged (CTL-SAL and DEP9-SAL) or not (CTL-NSAL and DEP9-NSAL). ESC or vehicle treatments began at weaning and lasted 24 days, when animals were sacrificed for determination of neurobiological variables or submitted to a battery of tests for evaluation of emotional behaviours. The results showed that BDNF levels were higher in SAL-challenged males and in DEP9-SAL females, whereas 5-HT receptor expression was reduced in DEP9 males and in SAL-challenged females. There were no changes in NPY or corticosterone levels. In the forced swim test, SAL-challenged males and DEP9 females displayed less immobility and ESC only increased social motivation in males. The results indicated that neonatal stress led to sex-dependent changes in neurobiology and behaviour and that chronic ESC treatment had minor effects on these parameters.

摘要

早期生活压力被认为是长期精神障碍发展的一个风险因素。母体剥夺(MD)是一种有用的范式,可以理解早期应激引起的神经发育轨迹变化的神经生物学基础。本研究的目的是研究慢性使用艾司西酞普兰(ESC)对经历 9 天大鼠期 MD(DEP9 组)并在 MD 结束时接受短暂轻度应激(盐水注射(SAL))挑战的雄性和雌性青春期大鼠海马脑源性神经营养因子(BDNF)和神经肽 Y(NPY)水平、5-羟色胺 1A 型受体(5-HT)表达、血浆皮质酮水平和情绪行为的影响。整个窝仔与母亲(CTL)一起饲养或进行 MD(DEP9)。在每个组中,幼仔都受到应激挑战(CTL-SAL 和 DEP9-SAL)或未受到应激挑战(CTL-NSAL 和 DEP9-NSAL)。ESC 或载体治疗在断奶时开始并持续 24 天,此时动物被处死以确定神经生物学变量或进行一系列情感行为测试。结果表明,SAL 挑战的雄性和 DEP9-SAL 的雌性 BDNF 水平较高,而 5-HT 受体表达在 DEP9 雄性和 SAL 挑战的雌性中降低。NPY 或皮质酮水平没有变化。在强迫游泳试验中,SAL 挑战的雄性和 DEP9 雌性的不动时间减少,ESC 仅增加雄性的社交动机。结果表明,新生期应激导致神经生物学和行为的性别依赖性变化,而慢性 ESC 治疗对这些参数的影响较小。

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