Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus

Hirofumi Noguchi, Ayaka Kimura, Naoya Murao, Taito Matsuda, Masakazu Namihira, Kinichi Nakashima

研究成果: ジャーナルへの寄稿記事

14 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)1-11
ページ数11
ジャーナルNeuroscience Research
95
DOI
出版物ステータス出版済み - 6 1 2015

Fingerprint

Neural Stem Cells
Methyltransferases
Hippocampus
Neurons
DNA
Neurogenesis
Dentate Gyrus
Maintenance
Parahippocampal Gyrus
Adult Stem Cells
DNA Methylation
Cell Survival
Cell Death
Learning
Enzymes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus. / Noguchi, Hirofumi; Kimura, Ayaka; Murao, Naoya; Matsuda, Taito; Namihira, Masakazu; Nakashima, Kinichi.

:: Neuroscience Research, 巻 95, 01.06.2015, p. 1-11.

研究成果: ジャーナルへの寄稿記事

@article{5927eeebf57b4be1acfb26a362e269d5,
title = "Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus",
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.",
author = "Hirofumi Noguchi and Ayaka Kimura and Naoya Murao and Taito Matsuda and Masakazu Namihira and Kinichi Nakashima",
year = "2015",
month = "6",
day = "1",
doi = "10.1016/j.neures.2015.01.014",
language = "English",
volume = "95",
pages = "1--11",
journal = "Neuroscience Research",
issn = "0168-0102",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus

AU - Noguchi, Hirofumi

AU - Kimura, Ayaka

AU - Murao, Naoya

AU - Matsuda, Taito

AU - Namihira, Masakazu

AU - Nakashima, Kinichi

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928215504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928215504&partnerID=8YFLogxK

U2 - 10.1016/j.neures.2015.01.014

DO - 10.1016/j.neures.2015.01.014

M3 - Article

C2 - 25659757

AN - SCOPUS:84928215504

VL - 95

SP - 1

EP - 11

JO - Neuroscience Research

JF - Neuroscience Research

SN - 0168-0102

ER -