Hydrogen sulfide mitigates memory impairments via the restoration of glutamatergic neurons in a mouse model of hemorrhage shock and resuscitation

• Published in: Experimental neurology 2024-06, Vol.376, p.114758-114758, Article 114758
• Main Authors: Song, Rong-Xin, Zhou, Ting-Ting, Jia, Shi-Yan, Li, Wen-Guang, Wang, Jun, Li, Bao-Dong, Shan, Yu-Dong, Zhang, Li-Min, Li, Xiao-Ming
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Glutamate; Glutamic Acid - metabolism; Glutamic Acid - toxicity; Hemorrhage shock and resuscitation; Hydrogen sulfide; Hydrogen Sulfide - pharmacology; Hydrogen Sulfide - therapeutic use; Male; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory Disorders - therapy; Mice; Mice, Inbred C57BL; Neurons - drug effects; Neurons - metabolism; Optogenetic activation; Optogenetics - methods; Shock, Hemorrhagic; Ventral tegmental area; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2024.114758

Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased β power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored β power. Moreover, hydrogen sulfide (H2S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H2S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased β power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H2S may be useful therapeutic approaches for improving memory deficits following HSR. •Hemorrhage shock and resuscitation induces memory impairments and decreases the activation in glutamatergic neurons.•Hemorrhage shock and resuscitation decreases β power in the VTA.•Hydrogen sulfide improve hemorrhage shock and resuscitation induced memory deficits.•Hydrogen sulfide elevates vesicular glutamate transporters neurons, increased β power.•Hydrogen sulfide has neuroprotective functions at physiological concentrations.