Supporting data for "Roles of DNA methylation on memory and serotonin neurotransmission in Alzheimer’s disease"

Alzheimer’s disease (AD) is becoming increasingly prevalent as the global population ages. Despite decades of research, the complex pathogenic mechanisms of AD remain largely elusive. In this thesis, the roles of hippocampal DNA methyltransferase 3a (DNMT3a) in mediating the pro-cognitive molecular changes of L-methionine (MET) were examined in 5xFAD mice by hippocampal specific knockdown of DNMT3a. It was shown that DNMT3a is necessary for MET-induced spatial memory enhancement, amyloid-β reduction, microgliosis reduction, and 5-HT fiber preservation in the hippocampus. Whether DNMT3a can modulate these processes independently from MET was further examined by hippocampal specific overexpression or knockdown of DNMT3a. Surprisingly, both manipulations were found to impair spatial memory, and such effects were seen in both wildtype and 5xFAD mice, suggesting that the physiological homeostasis of DNA methylation/demethylation processes is pivotal in normal memory functions. Moreover, overexpression and knockdown of DNMT3a were found to differentially affect amyloid-β deposition, microgliosis, and 5-HT neurotransmission in the hippocampus. Overall, findings in this thesis accentuated the important roles of DNA methylation in memory regulation in AD and established the brain 5-HT system as a viable target of DNA methylation modulating therapeutics for AD.