Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells

TY - JOUR

T1 - Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells

AU - Regnell, Christine Elisabeth

AU - Hildrestrand, Gunn Annette

AU - Sejersted, Yngve

AU - Medin, Tirill

AU - Moldestad, Olve

AU - Rolseth, Veslemøy

AU - Krokeide, Silje Zandstra

AU - Suganthan, Rajikala

AU - Luna, Luisa

AU - Bjørås, Magnar

AU - Bergersen, Linda H

N1 - Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2012/9/27

Y1 - 2012/9/27

N2 - Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.

AB - Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.

KW - Animals

KW - Anxiety/genetics

KW - Behavior, Animal/physiology

KW - Cognition/physiology

KW - DNA Damage

KW - DNA Repair/physiology

KW - Endodeoxyribonucleases/genetics

KW - Hippocampus/cytology

KW - Mice

KW - Mice, Knockout

KW - Nerve Tissue Proteins/genetics

KW - Neural Stem Cells/cytology

KW - Neurogenesis/physiology

KW - Oxidation-Reduction

U2 - 10.1016/j.celrep.2012.08.008

DO - 10.1016/j.celrep.2012.08.008

M3 - Journal article

C2 - 22959434

SN - 2211-1247

VL - 2

SP - 503

EP - 510

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -