Institute of Anatomy, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Center for Behavioral Brain Sciences CBBS, Magdeburg, Germany.
Eur J Neurosci. 2022 May;55(9-10):2142-2153. doi: 10.1111/ejn.15091. Epub 2021 Jan 1.
Early life stress is an important vulnerability factor for the development of anxiety disorders, depression and late-onset cognitive decline. Recently, we demonstrated that juvenile stress (JS) lastingly enhanced long-term potentiation via reduction of steady-state glutamine synthetase mRNA expression and the associated dysregulation of the astrocytic glutamate-glutamine cycle in the rat ventral CA1. We now investigated the regulation of steady-state mRNA expression of neuronal gene products that determine GABAergic and glutamatergic neurotransmission in layers of the ventral and dorsal CA1 after JS. We further studied their interaction with stress in young adult age (AS) to address their putative role in psychopathology development. Strikingly, mRNA levels of the glutamic acid decarboxylase (GAD) isoforms GAD65 and of the GABA-A receptor α2 (Gabra2) were increased after single JS or AS, but not after combined JS/AS stress experience. In fact, JS/AS resulted in layer-specific reduction of Gabra2 and also of Gabra1 mRNA levels in the ventral CA1. Furthermore, GAD65 and Gabra2 mRNAs were correlated with glutamatergic AMPA and NMDA receptor subunit mRNAs after single JS and AS, but not after combined JS/AS. Together, these data indicate a loss of allostatic regulation of steady-state mRNA levels of key GABAergic components that may result in a dysregulation of excitation/ inhibition balance in the ventral CA1 upon dual stress exposure. Finally, individual differences in local glucocorticoid receptor mRNA expression may contribute to this regulation.
早期生活压力是焦虑症、抑郁症和晚年认知衰退发展的一个重要脆弱性因素。最近，我们证明了青少年压力（JS）通过降低谷氨酸合成酶 mRNA 表达的稳态和相关的星形胶质细胞谷氨酸-谷氨酰胺循环失调，长期增强长时程增强。现在，我们研究了 JS 后 CA1 腹侧和背侧层中决定 GABA 能和谷氨酸能神经传递的神经元基因产物的稳态 mRNA 表达的调节。我们进一步研究了它们在年轻成年（AS）时与应激的相互作用，以解决它们在精神病理学发展中的潜在作用。引人注目的是，谷氨酸脱羧酶（GAD）同工型 GAD65 和 GABA-A 受体α2（Gabra2）的 mRNA 水平在单次 JS 或 AS 后增加，但在联合 JS/AS 应激体验后则不会。事实上，JS/AS 导致 CA1 腹侧层特异性减少 Gabra2 和 Gabra1 mRNA 水平。此外，GAD65 和 Gabra2 mRNAs 在单个 JS 和 AS 后与谷氨酸能 AMPA 和 NMDA 受体亚基 mRNAs 相关，但在联合 JS/AS 后则不相关。总之，这些数据表明，关键 GABA 能成分的稳态 mRNA 水平的稳态调节丧失，可能导致双重应激暴露时 CA1 腹侧兴奋/抑制平衡失调。最后，局部糖皮质激素受体 mRNA 表达的个体差异可能有助于这种调节。
