Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus. (June 2015)

• Record Type: Journal Article
• Authors: Noguchi, Hirofumi; Kimura, Ayaka; Murao, Naoya; Matsuda, Taito; Namihira, Masakazu; Nakashima, Kinichi
• Is Part Of: Neuroscience research. Volume 95(2015:Jun.)
• Page Start: 1
• Page End: 11
• Publication Date: 2015-06
• Subjects: DNA methyltransferase 1 -- Adult neurogenesis -- DNA methylation -- Neuronal survival -- Neural stem cells; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2015.01.014
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Dnmt1 is highly expressed in proliferative cells in the DG. Loss of DNMT1 in adult NS/PCs did not affect the proliferation and differentiation. Expression of DNMT1 in NS/PCs is important for survival of mature neurons. Abstract: Adult neurogenesis persists throughout life in the dentate gyrus (DG) of the hippocampus, and its importance has been highlighted in hippocampus-dependent learning and memory. Adult neurogenesis consists of multiple processes: maintenance and neuronal differentiation of neural stem/precursor cells (NS/PCs), followed by survival and maturation of newborn neurons and their integration into existing neuronal circuitry. However, the mechanisms that govern these processes remain largely unclear. Here we show that DNA methyltransferase 1 (DNMT1), an enzyme responsible for the maintenance of DNA methylation, is highly expressed in proliferative cells in the adult DG and plays an important role in the survival of newly generated neurons. Deletion of Dnmt1 in adult NS/PCs (aNS/PCs) did not affect the proliferation and differentiation of aNS/PCs per se . However, it resulted in a decrease of newly generated mature neurons, probably due to gradual cell death after aNS/PCs differentiated into neurons in the hippocampus. Interestingly, loss of DNMT1 in post-mitotic neurons did not influence their survival. Taken together, these findings suggest that the presence of DNMT1 in aNS/PCs is crucial for the survival of newly generated neurons, but is dispensable once they accomplish neuronal differentiation in the adult hippocampus.