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 in vitro 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 ( NEUROD1 ), Neural Cell Adhesion Molecule 1 ( NCAM1 ), Tubulin Beta 3 Class III ( TUBB3 ), RNA Binding Fox-1 Homolog 3 ( RBFOX3 ), Calbindin 1 ( CALB1 ), and Glial Fibrillary Acidic Protein ( GFAP ) 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 ( CNTNAP1 ), SEPT5-GP1BB Readthrough ( SEPT5-GP1BB ), T-Box Transcription Factor 5 ( TBX5 ), and Nucleoredoxin ( NXN ) genes were profiled by bisulfite pyrosequencing or bisulfite cloning sequencing; mRNA expression was also measured. NXN outlined a peak of DNA methylation overlapping type 3 neuroblasts. Aβ-treated NPCs showed transient decreases of mRNA expression for SEPT5-GP1BB and NXN on day 9 or 19 and an increase in DNA methylation on day 29 for NXN . NXN and SEPT5-GP1BB may reflect alterations detected in the brain of AD human patients, broadening our understanding of this disease.