Lin Lanyan, Zhang Jing, Dai Xiaoman, Xiao Nai'an, Ye Qinyong, Chen Xiaochun
Department of Geriatrics, Fujian Provincial Hospital, 134 Dongjie Road, Fuzhou 350001, China.
Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou 350005, China.
Brain Sci. 2022 Aug 15;12(8):1081. doi: 10.3390/brainsci12081081.
Stress may serve multiple roles in cerebral functioning, ranging from a highly appropriate behavioral adaptation to a critical risk factor for susceptibility to mood disorder and cognitive impairment. It is well known that E/I (excitation/inhibition) balance is essential for maintaining brain homeostasis. However, it remains largely unknown how GABAergic and Glutamatergic neurons respond to different stressful stimuli and whether the GABAergic-Glutamatergic neuron balance is related to the transition between adaptive and maladaptive behaviors. Here, we subjected 3-month-old mice to chronic mild stress (CMS) for a period of one, two, and four weeks, respectively. The results showed that the two-week CMS procedure produced adaptive effects on behaviors and cognitive performance, with a higher number of GABAergic neuron and VGluT1-positive neurons, increasing the expressions of p-GluN2B, Reelin, and syn-PSD-95 protein in the hippocampus. In contrast, the prolonged behavioral challenge (4 week) imposes a passive coping behavioral strategy and cognitive impairment, decreased the number of GABAergic neuron, hyperactivity of VGluT1-positive neuron, increased the ratio of p-GluN2B, and decreased the expression of Reelin, syn-PSD-95 in the hippocampus. These findings suggest that a moderate duration of stress probably promotes behavioral adaptation and spatial memory by maintaining a GABAergic-Glutamatergic neuron balance and promoting the expression of synaptic plasticity-related proteins in the brain.
应激在大脑功能中可能发挥多种作用，从高度恰当的行为适应到情绪障碍易感性和认知障碍的关键危险因素。众所周知，兴奋/抑制（E/I）平衡对于维持大脑内环境稳定至关重要。然而，γ-氨基丁酸能（GABAergic）和谷氨酸能（Glutamatergic）神经元如何应对不同的应激刺激，以及GABA能-谷氨酸能神经元平衡是否与适应性和适应不良行为之间的转变相关，在很大程度上仍不清楚。在此，我们分别对3月龄小鼠进行为期1周、2周和4周的慢性轻度应激（CMS）。结果表明，为期2周的CMS程序对行为和认知表现产生了适应性影响，GABA能神经元和VGlut1阳性神经元数量增加，海马体中p-GluN2B、Reelin和突触后密度蛋白95（syn-PSD-95）的表达增加。相比之下，长期的行为挑战（4周）导致被动应对行为策略和认知障碍，GABA能神经元数量减少，VGlut1阳性神经元活动亢进，p-GluN2B比例增加，海马体中Reelin、syn-PSD-95的表达减少。这些发现表明，适度时长的应激可能通过维持GABA能-谷氨酸能神经元平衡并促进大脑中突触可塑性相关蛋白的表达来促进行为适应和空间记忆。
