Electro-acupuncture alleviates adolescent cocaine exposure-enhanced anxiety-like behaviors in adult mice by attenuating the activities of PV interneurons in PrL
Electro-acupuncture alleviates adolescent cocaine exposure-enhanced anxiety-like behaviors in adult mice by attenuating the activities of PV interneurons in PrL
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电针通过减弱 PrL 中 PV 中间神经元的活动来减轻青少年可卡因暴露，增强成年小鼠的焦虑样行为
DOI：
10.1096/fj.202000346rr
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发表时间：
2020-07-19
期刊：
影响因子：
4.8
通讯作者：
Guan, Xiaowei
中科院分区：
文献类型：
--
作者：
Nie, Jiaxun;Wei, Xiaoyan;Guan, Xiaowei
我们最近发现，青少年可卡因暴露（ACE）导致增强的γ-氨基丁酸（GABA）神经递质系统在边缘前皮质（PrL）的成年小鼠。本研究旨在进一步探讨GABA能传递，尤其是PrL内的小白蛋白（PV）中间神经元在ACE诱导的焦虑样行为发展中的作用，并评估电针是否以及如何治疗ACE诱导的成年期异常行为。ACE小鼠在成年期表现出焦虑样行为的增强，伴随着GABA能传递和PrL PV中间神经元的增加。化学发生阻断PV中间神经元在PrL减轻ACE增强的小鼠焦虑样行为。电针印堂、百会穴37 d（2 Hz/100 Hz，1 mA，30 min，1次/d）也能减轻ACE诱导的焦虑样行为，挽救ACE损伤的GABA能神经递质系统和PV中间神经元。同时，电针可进一步抑制PrL锥体神经元的活动，提示电针可能通过“平静”整个PrL而对ACE诱导的异常情绪行为产生有益的影响。总的来说，这些研究结果表明，GABA能传递功能亢进，特别是由PV中间神经元介导的PrL可能是ACE诱导的焦虑样行为的关键病因。至少通过使GABA能和PV中间神经元的功能正常化，EA可能代表管理青少年物质使用相关情绪障碍的有前途的治疗策略。
We recently found that adolescent cocaine exposure (ACE) resulted in an enhancement of the gamma-aminobutyric acid (GABA) neurotransmitter system in the prelimbic cortex (PrL) of adult mice. Here, we aim to further investigate the role of GABAergic transmission, especially parvalbumin (PV) interneurons within PrL in the development of ACE-induced anxiety-like behavior, and to assess whether and how electro-acupuncture (EA) therapeutically manage the ACE-induced abnormal behaviors in adulthood. ACE mice exhibited the enhanced anxiety-like behaviors in their adulthood, accompanied by increased GABAergic transmission and PV interneurons in PrL. Chemogenetic blocking PV interneurons in PrL alleviated ACE-enhanced anxiety-like behaviors in mice. Importantly, 37-day EA treatments (mixture of 2 Hz/100 Hz, 1 mA, 30 minutes once a day) at the acupoints of Yintang (GV29) and Baihui (GV20) also alleviated ACE-induced anxiety-like behaviors, and rescued ACE-impaired GABAergic neurotransmitter system and PV interneurons in PrL. In parallel, EA treatments further suppressed the activities of pyramidal neurons in PrL, suggesting that EA treatments seem to perform it beneficial effects on the ACE-induced abnormal emotional behaviors by "calming down" the whole PrL. Collectively, these findings revealed that hyper-function of GABAergic transmission, especially mediating by PV interneurons in PrL may be key etiology underlying ACE-induced anxiety-like behaviors. At least by normalizing the function of GABAergic and PV interneurons, EA may represent a promising therapeutic strategy for managing adolescent substance use-related emotional disorders.