Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance.

Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance.
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DOI:
10.3389/fnins.2021.720286
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发表时间:
2021
影响因子:
4.3
通讯作者:
Chen Y
Chen Y
中科院分区:
医学2区
文献类型:
--
作者:
Chen Y;Zheng Y;Yan J;Zhu C;Zeng X;Zheng S;Li W;Yao L;Xia Y;Su WW;Chen Y

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早期生活压力被认为是情绪障碍的风险因素,尤其是抑郁和焦虑。虽然兴奋/抑制(E/I)失衡与神经精神疾病有关,但早期生活压力是否会影响不同发育阶段内侧前额叶皮层的E/I平衡尚不清楚。本研究采用行为测试、全细胞记录和微透析结合高效液相色谱-质谱(HPLC-MS)分析的方法,对暴露于母体分离(MS)环境中表现出良好早期生活应激模式的大鼠在青春期(出生后第43 - 60天)和成年期(第82 - 100天)的E/I平衡进行评估。首先,行为测试显示,MS在青春期大鼠中引起焦虑和抑郁样行为,而在成年大鼠中只引起抑郁样行为。其次,MS增加了青春期大鼠边缘前区L5锥体神经元突触传递的动作电位频率和E/I平衡,而降低了成年大鼠的动作电位频率和E/I平衡。最后,MS增加了青春期大鼠PrL锥体神经元的细胞外谷氨酸水平,降低了诱发兴奋性突触后电流(EPSCs)的成对脉冲比。相比之下,MS降低了成年大鼠PrL中细胞外谷氨酸水平,增加了锥体神经元中诱发EPSCs的成对脉冲比。目前的研究结果表明,E/I平衡在不同ms诱导的疾病中的关键作用可能与不同发育阶段突触前谷氨酸释放的可能性改变有关。
Early life stress is thought to be a risk factor for emotional disorders, particularly depression and anxiety. Although the excitation/inhibition (E/I) imbalance has been implicated in neuropsychiatric disorders, whether early life stress affects the E/I balance in the medial prefrontal cortex at various developmental stages is unclear. In this study, rats exposed to maternal separation (MS) that exhibited a well-established early life stress paradigm were used to evaluate the E/I balance in adolescence (postnatal day P43–60) and adulthood (P82–100) by behavior tests, whole-cell recordings, and microdialysis coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. First, the behavioral tests revealed that MS induced both anxiety- and depressive-like behaviors in adolescent rats but only depressive-like behavior in adult rats. Second, MS increased the action potential frequency and E/I balance of synaptic transmission onto L5 pyramidal neurons in the prelimbic (PrL) brain region of adolescent rats while decreasing the action potential frequency and E/I balance in adult rats. Finally, MS increases extracellular glutamate levels and decreased the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) of pyramidal neurons in the PrL of adolescent rats. In contrast, MS decreased extracellular glutamate levels and increased the paired-pulse ratio of evoked EPSCs of pyramidal neurons in the PrL of adult rats. The present results reveal a key role of E/I balance in different MS-induced disorders may related to the altered probability of presynaptic glutamate release at different developmental stages.
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