ABSTRACT

Over several decades, there is a growing evidence, which has shown that prenatal stress (PS) contributes to depression in offspring. Grape seed proanthocyanidins (GSPs), which contain dimers, trimers, oligomers of catechin and epicatechin, are known to possess antidepressant effects. The present study aimed to investigate the mechanism of antidepressant effects of GSPs on female juvenile prenatally stressed offspring rats. The results showed that the female juvenile offspring rats exposed to PS exhibited depression-like behavior manifested as longer immobility time and lesser consumption of sucrose solution. Prenatal stress reduced the number of hippocampal neurons and increased the level of the reactive oxygen species (ROS) in the hippocampus of the female juvenile offspring rats. Furthermore, the expression of PYD domains-containing protein 3 (NLRP3) and its downstream cytokines, Caspase-1, and interleukin-1β (IL-1β), were increased in the hippocampus of the female juvenile offspring rats exposed to PS. Administration of GSPs not only improved depression-like behavior and enhanced the number of hippocampal neurons, but also abated excessive ROS generation and inhibited the activation of the NLRP3-Caspase-1 signaling pathway. Taken together, GSPs counteract PS-induced hippocampal neuron loss and depression-like behavior by alleviating oxidative stress and NLRP3 activation. The present study provides a new insight for GSPs as an effective therapeutic agent for adolescent depression.

摘要

几十年来，越来越多的证据表明，产前压力（PS）会导致后代抑郁。葡萄籽原花青素（GSP）包含儿茶素和表儿茶素的二聚体，三聚体，低聚物，已知具有抗抑郁作用。本研究旨在探讨GSP对雌性幼年产前应激后代大鼠抗抑郁作用的机制。结果表明，暴露于PS的雌性幼仔大鼠表现出抑郁样行为，表现为固定时间更长和蔗糖溶液消耗更少。产前应激减少了雌性幼仔后代大鼠海马中海马神经元的数量并增加了活性氧（ROS）的水平。此外，在暴露于PS的雌性幼仔后代海马中，含有PYD域的蛋白3（NLRP3）及其下游细胞因子Caspase-1和白介素1β（IL-1β）的表达增加。GSPs的施用不仅改善了抑郁症样的行为并增加了海马神经元的数量，而且还减少了过多的ROS生成并抑制了NLRP3-Caspase-1信号通路的激活。总之，GSP通过减轻氧化应激和NLRP3激活来抵消PS诱导的海马神经元丢失和抑郁样行为。本研究为GSPs作为青少年抑郁症的有效治疗剂提供了新的见解。暴露于PS的雌性幼仔后代大鼠海马中的蛋白含量增加。GSPs的施用不仅改善了抑郁症样的行为并增加了海马神经元的数量，而且还减少了过多的ROS生成并抑制了NLRP3-Caspase-1信号通路的激活。总之，GSP通过减轻氧化应激和NLRP3激活来抵消PS诱导的海马神经元丢失和抑郁样行为。本研究为GSPs作为青少年抑郁症的有效治疗剂提供了新的见解。暴露于PS的雌性幼仔后代大鼠海马中的蛋白含量增加。GSPs的施用不仅改善了抑郁症样的行为并增加了海马神经元的数量，而且还减少了过多的ROS生成并抑制了NLRP3-Caspase-1信号通路的激活。总之，GSP通过减轻氧化应激和NLRP3激活来抵消PS诱导的海马神经元丢失和抑郁样行为。本研究为GSPs作为青少年抑郁症的有效治疗剂提供了新的见解。GSP通过减轻氧化应激和NLRP3激活来抵消PS诱导的海马神经元丢失和抑郁样行为。本研究为GSPs作为青少年抑郁症的有效治疗剂提供了新的见解。GSP通过减轻氧化应激和NLRP3激活来抵消PS诱导的海马神经元丢失和抑郁样行为。本研究为GSPs作为青少年抑郁症的有效治疗剂提供了新的见解。