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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Research Article

Sevoflurane Ameliorates Schizophrenia in a Mouse Model and Patients: A Pre-Clinical and Clinical Feasibility Study

Author(s): Tianyun Zhao, Ziwen Shi, Nongxi Ling, Jingwen Qin, Quancai Zhou, Lingzhi Wu, Yuansheng Wang, Chuansong Lin*, Daqing Ma* and Xingrong Song*

Volume 20, Issue 12, 2022

Published on: 08 June, 2022

Page: [2369 - 2380] Pages: 12

DOI: 10.2174/1570159X20666220310115846

Price: $65

Abstract

Background: GABAergic deficits have been considered to be associated with the pathophysiology of schizophrenia, and hence, GABA receptors subtype A (GABAARs) modulators, such as commonly used volatile anesthetic sevoflurane, may have therapeutic values for schizophrenia. The present study investigates the therapeutic effectiveness of low-concentration sevoflurane in MK801-induced schizophrenia-like mice and schizophrenia patients.

Methods: Three weeks after MK801 administration (0.5 mg kg-1, i.p. twice a day for 5 days), mice were exposed to 1% sevoflurane 1hr/day for 5 days. Behavioral tests, immunohistochemical analysis, western blot assay, and electrophysiology assessments were performed 1-week post-exposure. Ten schizophrenia patients received 1% sevoflurane 5 hrs per day for 6 days and were assessed with the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18) at week 1 and week 2.

Results: MK801 induced hypolocomotion and social deficits, downregulated expression of NMDARs subunits and postsynaptic density protein 95 (PSD95), reduced parvalbumin - and GAD67-positive neurons, altered amplitude and frequency of mEPSCs and mIPSCs, and increased the excitation/inhibition ratio. All these changes induced by MK-801 were attenuated by sevoflurane administration. Six and eight patients achieved a response defined as a reduction of at least 30% in the PANSS total score at 1st and 2nd week after treatments. The BPRS-18 total score was found to be significantly decreased by 38% at the 2nd week (p < 0.01).

Conclusion: Low-concentration sevoflurane effectively reversed MK801-induced schizophrenialike disease in mice and alleviated schizophrenia patients’ symptoms. Our work suggests sevoflurane to be a valuable therapeutic strategy for treating schizophrenia patients.

Keywords: Low-concentration, sevoflurane, E/I balance, social deficits, early response, schizophrenia.

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