NXN Gene Epigenetic Changes in an Adult Neurogenesis Model of Alzheimer's Disease

In view of the proven link between adult hippocampal neurogenesis (AHN) and learning and memory impairment, we generated a straightforward adult neurogenesis model to recapitulate DNA methylation marks in the context of Alzheimer's disease (AD). Neural progenitor cells (NPCs) were differentiated for 29 days and Aβ peptide 1-42 was added. mRNA expression of Neuronal Differentiation 1 (), Neural Cell Adhesion Molecule 1 (), Tubulin Beta 3 Class III (), RNA Binding Fox-1 Homolog 3 (), Calbindin 1 (), and Glial Fibrillary Acidic Protein () was determined by RT-qPCR to characterize the culture and framed within the multistep process of AHN. Hippocampal DNA methylation marks previously identified in Contactin-Associated Protein 1 (), SEPT5-GP1BB Readthrough (), T-Box Transcription Factor 5 (), and Nucleoredoxin () genes were profiled by bisulfite pyrosequencing or bisulfite cloning sequencing; mRNA expression was also measured. outlined a peak of DNA methylation overlapping type 3 neuroblasts. Aβ-treated NPCs showed transient decreases of mRNA expression for and on day 9 or 19 and an increase in DNA methylation on day 29 for . and may reflect alterations detected in the brain of AD human patients, broadening our understanding of this disease.