Electro-acupuncture alleviates METH withdrawal-induced spatial memory deficits by restoring astrocyte-derived glutamate uptake in dCA1 [article]

Pengbo Shi, Zhaosu Li, Xing Xu, Jiaxun Nie, Dekang Liu, Qinglong Cai, Yonghua Zhao, Yun Guan, Feifei Ge, Xiaowei Guan
2020 bioRxiv   pre-print
AbstractMethamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains unclear. Here, we investigated the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the METH withdrawal-induced spatial memory deficits. METH withdrawal weakened astrocytic capacity of Glu uptake, but
more » ... ailed to change Glu release from dCA3, resulting in hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a novel target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.
doi:10.1101/2020.05.20.106153 fatcat:gxnyi7tlgrclrfmdd3zn5pkueq