da Costa Vinícius Fresca, Ramírez Johana Caterin Caipa, Ramírez Stephany Viatela, Avalo-Zuluaga Julian Humberto, Baptista-de-Souza Daniela, Canto-de-Souza Lucas, Planeta Cleopatra S, Rodríguez Javier Leonardo Rico, Nunes-de-Souza Ricardo Luiz
Laboratory of Pharmacology, School of Pharmaceutical Sciences, University Estadual Paulista, UNESP, Araraquara, Brazil.
Joint Graduate Program in Physiological Sciences (PIPGCF) UFSCar-UNESP, São Carlos, Brazil.
Front Integr Neurosci. 2023 Jun 12;17:1168640. doi: 10.3389/fnint.2023.1168640. eCollection 2023.
Chronic exposure to social defeat stress (SDS) has been used to investigate the neurobiology of depressive- and anxiety-like responses and mnemonic processes. We hypothesized that these affective, emotional, and cognitive consequences induced by SDS are regulated via glutamatergic neurons located in the bed nucleus of the stria terminalis (BNST), amygdaloid complex, and hippocampus in mice.
Here, we investigated the influence of chronic SDS on (i) the avoidance behavior assessed in the social interaction test, (ii) the anxiety-like behavior (e.g., elevated plus-maze, and open field tests) (iii) depressive-like behaviors (e.g., coat state, sucrose splash, nesting building, and novel object exploration tests), (iv) the short-term memory (object recognition test), (v) ΔFosB, CaMKII as well as ΔFosB + CaMKII labeling in neurons located in the BNST, amygdaloid complex, dorsal (dHPC) and the ventral (vHPC) hippocampus.
The main results showed that the exposure of mice to SDS (a) increased defensive and anxiety-like behaviors and led to memory impairment without eliciting clear depressive-like or anhedonic effects; (b) increased ΔFosB + CaMKII labeling in BNST and amygdala, suggesting that both areas are strongly involved in the modulation of this type of stress; and produced opposite effects on neuronal activation in the vHPC and dHPC, i.e., increasing and decreasing, respectively, ΔFosB labeling. The effects of SDS on the hippocampus suggest that the vHPC is likely related to the increase of defensive- and anxiety-related behaviors, whereas the dHPC seems to modulate the memory impairment.
Present findings add to a growing body of evidence indicating the involvement of glutamatergic neurotransmission in the circuits that modulate emotional and cognitive consequences induced by social defeat stress.
长期暴露于社会挫败应激（SDS）已被用于研究抑郁样和焦虑样反应以及记忆过程的神经生物学机制。我们假设，SDS诱导的这些情感、情绪和认知后果是通过位于小鼠终纹床核（BNST）、杏仁复合体和海马体中的谷氨酸能神经元来调节的。
在此，我们研究了慢性SDS对以下方面的影响：（i）在社会互动测试中评估的回避行为；（ii）焦虑样行为（例如，高架十字迷宫和旷场试验）；（iii）抑郁样行为（例如，被毛状态、蔗糖偏好、筑巢和新物体探索试验）；（iv）短期记忆（物体识别试验）；（v）BNST、杏仁复合体、背侧（dHPC）和腹侧（vHPC）海马体中神经元的ΔFosB、CaMKII以及ΔFosB + CaMKII标记。
主要结果表明，将小鼠暴露于SDS会：（a）增加防御性和焦虑样行为，并导致记忆障碍，但未引发明显的抑郁样或快感缺失效应；（b）增加BNST和杏仁核中的ΔFosB + CaMKII标记，表明这两个区域都强烈参与了这种应激类型的调节；并且对vHPC和dHPC中的神经元激活产生相反的影响，即分别增加和减少ΔFosB标记。SDS对海马体的影响表明，vHPC可能与防御性和焦虑相关行为的增加有关，而dHPC似乎调节记忆障碍。
目前的研究结果增加了越来越多的证据，表明谷氨酸能神经传递参与了调节社会挫败应激诱导的情绪和认知后果的神经回路。
