Sodium hydrosulfide reverses β2-microglobulin-induced depressive-like behaviors of male Sprague-Dawley rats: Involving improvement of synaptic plasticity and enhancement of Warburg effect in hippocampus

San-Qiao Yang; Yi-Yun Tang; Dan Zeng; Qing Tian; Hai-Jun Wei; Chun-Yan Wang; Ping Zhang; Yong-Jun Chen; Wei Zou; Xiao-Qing Tang

doi:10.1016/j.bbr.2021.113562

Sodium hydrosulfide reverses β₂-microglobulin-induced depressive-like behaviors of male Sprague-Dawley rats: Involving improvement of synaptic plasticity and enhancement of Warburg effect in hippocampus

Behav Brain Res. 2022 Jan 24:417:113562. doi: 10.1016/j.bbr.2021.113562. Epub 2021 Sep 6.

Authors

Affiliations

¹ Institute of Neurology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China.
² Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China.
³ Department of Neurology, Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang 421001, Hunan, PR China.
⁴ Institute of Neurology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address: tangxq-usc@qq.com.

PMID: 34499939
DOI: 10.1016/j.bbr.2021.113562

Abstract

Background: Our previous works demonstrated that β2-microglobulin (β2m), a systemic pro-aging factor, induce depressive-like behaviors. Hydrogen sulfide (H₂S) is identified as a potential target for treatment of depression. The aim of the present work is to explore whether H₂S antagonizes β2m-induced depressive-like behaviors and the underlying mechanisms.

Methods: The depressive-like behaviors were detected using the novelty suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The expressions of Warburg-related proteins, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), Lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase 1(PDK1), and synaptic plasticity-related proteins, including postsynaptic density protein 95 (PSD95) and synaptophysin1 (SYN1), were determined by western blotting.

Result: we found that NaHS (the donor of H₂S) attenuated the depressive-like behaviors in the β2m-exposed rats, as judged by NSFT, TST, FST, and OFT. We also demonstrated that NaHS enhanced the synaptic plasticity, as evidenced by the upregulations of PSD95 and SYN1 expressions in the hippocampus of β2m-exposed rats. Furthermore, NaHS improved the Warburg effect in the hippocampus of β2m-exposed rats, as evidenced by the upregulations of HK II, PKM2, LDHA and PDK1 expressions, and the downregulation of PDH expression.

Conclusion: H₂S prevents β2m-induced depressive-like behaviors, which is involved in improvement of hippocampal synaptic plasticity as a result of enhancement of hippocampal Warburg effect.

Keywords: Depressive-like behavior; Hydrogen sulfide; Synaptic plasticity; Warburg effect; β2-microglobulin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Multiple*
Animals
Cataract / congenital*
Cornea / abnormalities*
Depression* / chemically induced
Depression* / drug therapy
Hippocampus / drug effects*
Hypogonadism*
Intellectual Disability*
Male
Microcephaly*
Neuronal Plasticity / drug effects*
Optic Atrophy*
Rats
Rats, Sprague-Dawley
Sulfides / pharmacology*
beta 2-Microglobulin / adverse effects*

Substances

Sulfides
beta 2-Microglobulin
sodium bisulfide

Supplementary concepts

Warburg Sjo Fledelius syndrome