title: Homocysteine homeostasis and betaine-homocysteine S-methyltransferase expression in the brain of hibernating bats.
abstract: Elevated homocysteine is an important risk factor that increases cerebrovascular and neurodegenerative disease morbidity. In mammals, B vitamin supplementation can reduce homocysteine levels. Whether, and how, hibernating mammals, that essentially stop ingesting B vitamins, maintain homocysteine metabolism and avoid cerebrovascular impacts and neurodegeneration remain unclear. Here, we compare homocysteine levels in the brains of torpid bats, active bats and rats to identify the molecules involved in homocysteine homeostasis. We found that homocysteine does not elevate in torpid brains, despite declining vitamin B levels. At low levels of vitamin B6 and B12, we found no change in total expression level of the two main enzymes involved in homocysteine metabolism (methionine synthase and cystathionine β-synthase), but a 1.85-fold increase in the expression of the coenzyme-independent betaine-homocysteine S-methyltransferase (BHMT). BHMT expression was observed in the amygdala of basal ganglia and the cerebral cortex where BHMT levels were clearly elevated during torpor. This is the first report of BHMT protein expression in the brain and suggests that BHMT modulates homocysteine in the brains of hibernating bats. BHMT may have a neuroprotective role in the brains of hibernating mammals and further research on this system could expand our biomedical understanding of certain cerebrovascular and neurodegenerative disease processes.
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute for Advanced Studies in Multidisciplinary Science and Technology, East China Normal University, Shanghai, China.
authors.forename: Yijian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute for Advanced Studies in Multidisciplinary Science and Technology, East China Normal University, Shanghai, China.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute for Advanced Studies in Multidisciplinary Science and Technology, East China Normal University, Shanghai, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute for Advanced Studies in Multidisciplinary Science and Technology, East China Normal University, Shanghai, China.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Pan
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute for Advanced Studies in Multidisciplinary Science and Technology, East China Normal University, Shanghai, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002685:Chiroptera / Q000378:metabolism* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006605:Hibernation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006710:Homocysteine / Q000378:metabolism*; D007150:Immunohistochemistry; D008954:Models, Biological; D051381:Rats; D013045:Species Specificity
chemical_list: D006710:Homocysteine; D050940:Betaine-Homocysteine S-Methyltransferase