Homocysteine restrains hippocampal neurogenesis in focal ischemic rat brain by inhibiting DNA methylation

The Role of DNA Methylation in Stroke Recovery

“…Among the mechanisms of neuronal recovery after stroke, regulation of neurogenesis-inducing DNA methylation induces hypermethylation of galanin and Ng2 gene promoters via DNMT upregulation, and global DNA methylation is also increased [ 81 ]. However, demethylation also in the galanin and Ng2 promoter regions increases with increasing TET1 [ 79 ].…”

“…Related studies have demonstrated that Hcy inhibits the self-renewal capacity of neural stem cells (NSCs). This was confirmed by the Hcy-induced reduction in the number of new immature neurons co-expressing doublecortin (DCX) and 5-bromo-2′-deoxyuridine (BrdU) and of newly regenerated mature neurons co-expressing neuronal nuclear antigen (NeuN) and BrdU in the hippocampus [ 81 ]. Neurogenesis levels are frequently assessed using DCX, a microtubule-associated protein expressed in developing neurons and migrating neuroblasts [ 81 , 82 ].…”

“…This was confirmed by the Hcy-induced reduction in the number of new immature neurons co-expressing doublecortin (DCX) and 5-bromo-2′-deoxyuridine (BrdU) and of newly regenerated mature neurons co-expressing neuronal nuclear antigen (NeuN) and BrdU in the hippocampus [ 81 ]. Neurogenesis levels are frequently assessed using DCX, a microtubule-associated protein expressed in developing neurons and migrating neuroblasts [ 81 , 82 ]. NeuN, a recognized neuron-specific marker, is used to assess newly formed hippocampal neurons, and BrdU is used to identify newly divided cells [ 81 , 83 ].…”

“…Neurogenesis levels are frequently assessed using DCX, a microtubule-associated protein expressed in developing neurons and migrating neuroblasts [ 81 , 82 ]. NeuN, a recognized neuron-specific marker, is used to assess newly formed hippocampal neurons, and BrdU is used to identify newly divided cells [ 81 , 83 ]. When DNMT activity, global 5mC levels, and intracellular 5mC levels in newly generated cells were measured in Hcy-treated MCAO ischemic brains to confirm the role of DNMT and DNA methylation in Hcy-induced nerve regeneration, decreased DNMT activity, reduced total methylation levels, and reduced numbers of neurons co-expressing 5mC and NeuN or DCX and 5mC were observed.…”

“…When DNMT activity, global 5mC levels, and intracellular 5mC levels in newly generated cells were measured in Hcy-treated MCAO ischemic brains to confirm the role of DNMT and DNA methylation in Hcy-induced nerve regeneration, decreased DNMT activity, reduced total methylation levels, and reduced numbers of neurons co-expressing 5mC and NeuN or DCX and 5mC were observed. A reduction in DNMT activity, which is mainly mediated by S -adenosylmethionine (SAM) and S -adenosylhomocysteine (SAH) concentrations, may produce Hcy-induced DNA hypomethylation [ 81 , 84 , 85 ]. According to these studies, the neurogenesis mechanism in stroke recovery can be enhanced by regulating DNMT activity, which is inhibited by the increased Hcy levels after stroke.…”