Title:Sevoflurane Ameliorates Schizophrenia in a Mouse Model and Patients: A
Pre-Clinical and Clinical Feasibility Study
Volume: 20
Issue: 12
Author(s): Tianyun Zhao, Ziwen Shi, Nongxi Ling, Jingwen Qin, Quancai Zhou, Lingzhi Wu, Yuansheng Wang, Chuansong Lin*, Daqing Ma*Xingrong Song*
Affiliation:
- Department of Psychiatry, The Third People's Hospital of Xinhui District, Guangdong, China
- Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial
College London, Chelsea and Westminster Hospital, London, UK
- Department of Anesthesiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University,
Guangzhou, China
Keywords:
Low-concentration, sevoflurane, E/I balance, social deficits, early response, schizophrenia.
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.
