Hydrogen sulfide attenuates homocysteine-induced cognitive deficits and neurochemical alterations by improving endogenous hydrogen sulfide levels

Abstract

Hyperomocysteinemia (HHcy) has been associated with mild cognitive impairment and dementia. Hydrogen sulfide (H₂ S) has been suggested to be an endogenous modulator of neuronal functions. However, the effect and mechanisms involved in beneficial effect of H₂ S has not been investigated in homocysteine (Hcy)-induced cognitive deficits. This study has been designed to evaluate the effect of exogenous H₂ S on behavioral deficits and neurochemical alterations in HHcy animals. Hcy levels were significantly elevated in plasma, cortex, and hippocampus of Hcy administered animals. A progressive decline in memory functions and increased anxiolytic behavior was observed in HHcy animals. This was accompanied by decrease in endogenous H₂ S levels along with decreased activity of cystathionase (CSE) and cystathionine β-synthase (CBS). However, a significant increase in CSE and CBS mRNAs was observed. In addition, the catecholamine and serotonin levels were reduced and the activity of monoamine oxidase A and B were increased in brain regions of HHcy animals. Haematoxylin and eosin staining revealed higher number of pyknotic cells in brain regions of HHcy animals. H₂ S administration was found to lower elevated plasma and brain Hcy levels. The activities of CBS, CSE, and levels of H₂ S were restored in HHcy animals administered H₂ S. Exogenous H₂ S also ameliorated behavioral deficits accompanied by significant increase in catecholamines. Histological analysis revealed normal cell morphology in Hcy-treated animals supplemented with H₂ S. These results clearly demonstrate that the protective effect of H₂ S on Hcy-induced cognitive deficits is mediated through increased catecholamine and H₂ S levels thereby suggesting its beneficial role in preventing HHcy-induced neurodegeneration. © 2016 BioFactors, 43(3):434-450, 2017.

Keywords: behavior; catecholamines; homocysteine; hydrogen sulfide; hyperhomocysteinemia; neurotransmitters.