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.

Insights in the regulation of trimetylamine N-oxide production using a comparative biomimetic approach suggest a metabolic switch in hibernating bears

“…However, as we observed no significant increase in homocysteine levels during hibernation (Table 1), high betaine may protect against hyperhomocysteinemia by re-methylation of homocysteine 42 . Accordingly, homocysteine does not elevate in bat (Myotis pilosus) brains during torpor due to increased expression of betaine-homocysteine S-methyltransferase 43 .…”

Large captivity effect based on gene expression comparisons between captive and wild shrew brains

“…This captive effect in shrew brain transcription corroborates previously identified gene expression responses in a limited, yet diverse number of organisms and tissues, including the brains of cane toad and house sparrows (7, 49) freshwater mussel gill (50), zooplankton (51), and the liver of an anoline lizard (52). While some studies have identified domestication-associated neural changes in subsets of mammals (53–55) many have focused on other sources of environmental change such as hypoxia (56, 57), metabolism (56, 58, 59), temperature, feeding behavior (60), stress (61), photoperiod (62, 63), and activity (64). And yet, no experiment analyzing expression divergence has been conducted on captive mammal brains, despite their use in clinical and ecological experimentation.…”

Effects of Partially Defatted Hermetia illucens Meal in Rainbow Trout Diet on Hepatic Methionine Metabolism

“…BHMT and CBS have different affinities for their substrate (Hcy): BHMT has a high affinity (low Michaelis constant, KM, values) and can utilize Hcy at a relatively low concentration [ 27 ], whereas CBS has low affinity in the catabolic pathway. Thus, dysfunction of CBS causes higher levels of Hcy in the blood than does BHMT.…”