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Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) has been suggested to be an endogenous modulator of neuronal functions. However, the effect and mechanisms involved in beneficial effect of H<jats:sub>2<\/jats:sub>S has not been investigated in homocysteine (Hcy)\u2010induced cognitive deficits. This study has been designed to evaluate the effect of exogenous H<jats:sub>2<\/jats:sub>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 H<jats:sub>2<\/jats:sub>S levels along with decreased activity of cystathionase (CSE) and cystathionine \u03b2\u2010synthase (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. H<jats:sub>2<\/jats:sub>S administration was found to lower elevated plasma and brain Hcy levels. The activities of CBS, CSE, and levels of H<jats:sub>2<\/jats:sub>S were restored in HHcy animals administered H<jats:sub>2<\/jats:sub>S. Exogenous H<jats:sub>2<\/jats:sub>S also ameliorated behavioral deficits accompanied by significant increase in catecholamines. Histological analysis revealed normal cell morphology in Hcy\u2010treated animals supplemented with H<jats:sub>2<\/jats:sub>S. These results clearly demonstrate that the protective effect of H<jats:sub>2<\/jats:sub>S on Hcy\u2010induced cognitive deficits is mediated through increased catecholamine and H<jats:sub>2<\/jats:sub>S levels thereby suggesting its beneficial role in preventing HHcy\u2010induced neurodegeneration. \u00a9 2016 BioFactors, 43(3):434\u2013450, 2017<\/jats:p>","DOI":"10.1002\/biof.1354","type":"journal-article","created":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T09:40:40Z","timestamp":1491817240000},"page":"434-450","source":"Crossref","is-referenced-by-count":41,"title":["Hydrogen sulfide attenuates homocysteine\u2010induced cognitive deficits and neurochemical alterations by improving endogenous hydrogen sulfide levels"],"prefix":"10.1002","volume":"43","author":[{"given":"Mohit","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biochemistry Panjab University Chandigarh 160014 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manish","family":"Modi","sequence":"additional","affiliation":[{"name":"Department of Neurology Postgraduate Institute of Medical Education and Research Chandigarh 160012 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajat","family":"Sandhir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Panjab University Chandigarh 160014 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.24.012003.132418"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.166421"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081036"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.06.021"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00438-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.06.021"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.6.861"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652409787847146"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12424"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.07.023"},{"key":"e_1_2_8_12_1","first-page":"7","article-title":"The methionine\u2010homocysteine cycle and its effects on cognitive diseases","volume":"8","author":"Miller A. 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