Adult neurogenesis was one of the most important discoveries of the last century, helping us to better understand brain function. Researchers recently discovered that microglia play an important role in this process. However, various questions remain concerning where, at what stage, and what types of microglia participate. In this review, we demonstrate that certain pools of microglia are determinant cells in different phases of the generation of new neurons. This sheds light on how cells cooperate in order to fine tune brain organization. It also provides us with a better understanding of distinct neuronal pathologies.

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.

Adult hippocampal neurogenesis (AHN) study is still a challenge. In addition to methodological difficulties is the controversy of results derived of human or animal system approaches. In view of the proven link between AHN and learning and memory impairment, we generated a straightforward in vitro model to recapitulate adult neurogenesis in the context of Alzheimer’s disease (AD). Neural progenitor cells (NPCs) monolayer culture was differentiated for a period of 29 days and Aβ peptide 1-42 was administered once a week. mRNA expression of NEUROD1, NCAM1, TUBB3, RBFOX3, CALB1 and GFAP genes was determined by RT-qPCR. Phenotypic changes were observed during directed differentiation. Except for GFAP and CALB1 , these changes correlated with altered expression profile of all genes since 9 days. Only TUBB3 expression remained constant while NEUROD1, NCAM1 and RBFOX3 expression increased over time. Moreover, Aβ treated NPCs showed transient decreases of mRNA expression for NCAM1, TUBB3 and RBFOX3 genes at 9 or 19 days. Our in vitro human NPCs model is framed within the multistep process of AHN in the SGZ of the DG. Remarkably, its transcriptional assessment might reflect alterations detected in AD human patients, deepening our understanding of the disorder and possibly of its pathogenesis. SUMMARY STATEMENT: Transcriptional profile of a number of genes recapitulating particular stages of Adult hippocampal neurogenesis in the context of Alzheimer’s disease