Electroacupuncture alleviates spatial memory deficits in METH withdrawal mice by enhancing astrocyte-mediated glutamate clearance in the dCA1
Electroacupuncture alleviates spatial memory deficits in METH withdrawal mice by enhancing astrocyte-mediated glutamate clearance in the dCA1
复制标题
电针通过增强 dCA1 中星形胶质细胞介导的谷氨酸清除率来减轻 METH 戒断小鼠的空间记忆缺陷
DOI：
10.1111/adb.13068
复制
发表时间：
2021-06-14
影响因子：
3.4
通讯作者：
Guan, Xiaowei
中科院分区：
文献类型：
--
作者：
He, Teng;Li, Nanqin;Guan, Xiaowei
甲基苯丙胺在大脑中引起内源性谷氨酸，这可以部分解释甲基苯丙胺引起的记忆障碍。在此，我们研究了电针(EA)对冰毒戒断小鼠空间记忆障碍的治疗作用及其潜在的突触机制。我们发现电针“百会”和“银塘穴”可以改善冰毒戒断小鼠的空间记忆障碍。同时，电针还能降低体内谷氨酸水平，抑制戒断小鼠dCA1区神经元的活动，表现为c-Fos水平和mEPSP波幅的降低。在dCA1区，电针使A1样星形胶质细胞减少，但增加谷氨酸转运体1和谷氨酰胺合成酶等星形胶质细胞谷氨酸能转运分子。然而，电针对dCA3区突触前Glu的传递似乎没有影响，这从电针治疗和假电针治疗的冰毒戒断小鼠dCA3神经元中c-Fos的相似水平、dCA3神经末梢的突触泡泡标记和dCA1神经元中的双脉冲比率值来证明。这些发现表明，电针可能至少部分通过促进星形胶质细胞介导的谷氨酸清除而使dCA1谷氨酸水平正常化。综上所述，星形胶质细胞可能是开发针对冰毒使用者受损记忆行为的治疗干预措施的新靶点，而电针代表着一种很有前途的非侵入性治疗策略，用于管理药物引起的记忆缺陷。
Methamphetamine (METH) elicits endogenous glutamate (Glu) in the brain, which could partially explain METH-induced memory deficits. Here, we investigated the therapeutic effects of electroacupuncture (EA) on spatial memory deficits in METH withdrawal mice and its potential synaptic mechanisms. We found that EA at acupoints 'Baihui' and 'Yintang' ameliorated the impaired spatial memory in METH withdrawal mice. In parallel, EA attenuated the Glu levels in vivo and suppressed the neuronal activities within dCA1 of METH withdrawal mice, as indicated by the decreasing c-Fos levels and the amplitude of mEPSP. In the dCA1, EA decreased A1-like astrocytes but increased astrocytic glutamatergic transporting molecules including glutamate transporter 1 and glutamine synthase. However, EA seemed to have no effects on presynaptic Glu transmission from the dCA3, as evidenced by the similiar levels of c-Fos in the dCA3 neurons, synaptic vesicular markers of dCA3 neural terminals and values of paired-pulse ratio in the dCA1 neurons between EA-treated and sham EA-treated METH withdrawal mice. These findings suggest that EA might normalize the dCA1 Glu levels at least in part through enhancing astrocyte-mediated Glu clearance. Taken together, astrocytes might be a novel target for developing therapeutic interventions against the impaired memory behaviours in METH users, and EA represents a promising non-invasive therapeutic strategy for the management of drug-caused memory deficits.