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bioRxiv · 10.1101/2020.05.20.106153

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

Shi, P.·Li, Z.·Xu, X.·Nie, J.·Liu, D.·Cai, Q.·Zhao, Y.·Guan, Y.·Ge, F.·Guan, X.
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Abstract

Methamphetamine (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 incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to 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 key 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.

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Shi, P., Li, Z., Xu, X., Nie, J., Liu, D., Cai, Q., Zhao, Y., Guan, Y., Ge, F., Guan, X.. 2020-05-22. Electro-acupuncture alleviates METH withdrawal-induced spatial memory deficits by restoring astrocyte-derived glutamate uptake in dCA1. https://doi.org/10.1101/2020.05.20.106153

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