Dandi Evgenia, Kesidou Evangelia, Simeonidou Constantina, Spandou Evangelia, Grigoriadis Nikolaos, Tata Despina A
Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Brain Sci. 2024 Apr 3;14(4):357. doi: 10.3390/brainsci14040357.
Stress-related mental disorders have become increasingly prevalent, thus endangering mental health worldwide. Exploring stress-associated brain alterations is vital for understanding the possible neurobiological mechanisms underlying these changes. Based on existing evidence, the brain endogenous cannabinoid system (ECS) plays a significant role in the stress response, and disruptions in its function are associated with the neurobiology of various stress-related disorders. This study primarily focuses on investigating the impact of chronic unpredictable stress (CUS) on the expression of hippocampal cannabinoid type 1 (CB) receptors, part of the ECS, in adult male and female Wistar rats. Additionally, it explores whether environmental enrichment (EE) initiated during adolescence could mitigate the CUS-associated alterations in CB expression. Wistar rats, shortly after weaning, were placed in either standard housing (SH) or EE conditions for a duration of 10 weeks. On postnatal day 66, specific subgroups of SH or EE animals underwent a 4-week CUS protocol. Western blot (WB) analysis was conducted in the whole hippocampus of the left brain hemisphere to assess total CB protein expression, while immunohistochemistry (IHC) was performed on the right hemisphere to estimate the expression of CB receptors in certain hippocampal areas (i.e., CA1, CA3 and dentate gyrus-DG). The WB analysis revealed no statistically significant differences in total CB protein levels among the groups; however, reduced CB expression was found in specific hippocampal sub-regions using IHC. Specifically, CUS significantly decreased CB receptor expression in the CA1 and DG of both sexes, whereas in CA3 the CUS-associated decrease was limited to SH males. Interestingly, EE housing proved protective against these reductions. These findings suggest a region and sex-specific endocannabinoid response to chronic stress, emphasizing the role of positive early experiences in the protection of the adolescent brain against adverse conditions later in life.
与压力相关的精神障碍日益普遍，从而危及全球心理健康。探索与压力相关的大脑改变对于理解这些变化背后可能的神经生物学机制至关重要。基于现有证据，大脑内源性大麻素系统（ECS）在应激反应中起重要作用，其功能紊乱与各种与压力相关疾病的神经生物学有关。本研究主要关注慢性不可预测应激（CUS）对成年雄性和雌性Wistar大鼠海马大麻素1型（CB）受体（ECS的一部分）表达的影响。此外，还探讨了青春期开始的环境富集（EE）是否可以减轻与CUS相关的CB表达改变。刚断奶的Wistar大鼠被置于标准饲养（SH）或EE条件下10周。在出生后第66天，SH或EE动物的特定亚组接受为期4周的CUS方案。在左脑半球的整个海马体中进行蛋白质免疫印迹（WB）分析以评估总CB蛋白表达，而在右半球进行免疫组织化学（IHC）以估计某些海马区域（即CA1、CA3和齿状回-DG）中CB受体的表达。WB分析显示各组之间总CB蛋白水平无统计学显著差异；然而，使用IHC发现在特定海马亚区域CB表达降低。具体而言，CUS显著降低了两性CA1和DG中的CB受体表达，而在CA3中，与CUS相关的降低仅限于SH雄性。有趣的是，EE饲养被证明对这些降低有保护作用。这些发现表明内源性大麻素对慢性应激的反应具有区域和性别特异性，强调了积极的早期经历在保护青少年大脑免受生命后期不利条件影响方面的作用。
