Gadd45b and N-methyl-D-aspartate induced DNA demethylation in postmitotic neurons

Gadd45b 和 N-甲基-D-天冬氨酸诱导有丝分裂后神经元的 DNA 去甲基化

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作者:David P Gavin, Handojo Kusumo, Rajiv P Sharma, Marina Guizzetti, Alessandro Guidotti, Subhash C Pandey

Aim

In nondividing neurons examine the role of Gadd45b in active 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) removal at a gene promoter highly implicated in mental illnesses and cognition, Bdnf. Materials &

Conclusion

These results contribute to our understanding of DNA demethylation mechanisms in neurons, and its role in regulating NMDA responsive genes implicated in mental illnesses.

Methods

Mouse primary cortical neuronal cultures with and without Gadd45b siRNA transfection were treated with N-methyl-d-aspartate (NMDA). Expression changes of genes reportedly involved in DNA demethylation, Bdnf mRNA and protein and 5MC and 5HMC at Bdnf promoters were measured.

Results

Gadd45b siRNA transfection in neurons abolishes the NMDA-induced increase in Bdnf IXa mRNA and reductions in 5MC and 5HMC at the Bdnf IXa promoter.

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