The possible role of hydrogen sulfide as an endogenous neuromodulator

TLDR

Hydrogen sulfide is endogenously produced from L‑cysteine, is abundant in the brain, and, like nitric oxide and carbon monoxide, is thought to act as a neuronal messenger. The study aimed to determine whether the enzyme cystathionine β‑synthase (CBS) contributes to brain H₂S production. By demonstrating high CBS expression in the hippocampus and showing that CBS inhibitors reduce while a CBS activator increases H₂S levels, the authors linked CBS activity to endogenous H₂S synthesis. Physiological H₂S concentrations selectively potentiated NMDA receptor responses and promoted hippocampal long‑term potentiation, indicating that endogenous H₂S functions as a neuromodulator.

Abstract

Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously from L-cysteine in mammalian tissues. H2S is present at relatively high levels in the brain, suggesting that it has a physiological function. Two other gases, nitric oxide and carbon monoxide, are also endogenously produced and have been proposed as neuronal messengers in the brain. In this work we show the following: (1) an H2S-producing enzyme, cystathionine beta-synthase (CBS), is highly expressed in the hippocampus; (2) CBS inhibitors hydroxylamine and amino-oxyacetate suppress the production of brain H2S; and (3) a CBS activator, S-adenosyl-L-methionine, enhances H2S production, indicating that CBS contributes to the production of endogenous H2S. We also show that physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and facilitate the induction of hippocampal long-term potentiation. These observations suggest that endogenous H2S functions as a neuromodulator in the brain.