TY - JOUR

T1 - NEIL1 stimulates neurogenesis and suppresses neuroinflammation after stress

AU - Yang, Beimeng

AU - Figueroa, David M.

AU - Hou, Yujun

AU - Babbar, Mansi

AU - Baringer, Stephanie L.

AU - Croteau, Deborah L.

AU - Bohr, Vilhelm A.

PY - 2019

Y1 - 2019

N2 - Cellular exposure to ionizing radiation leads to oxidatively generated DNA damage, which has been implicated in neurodegenerative diseases. DNA damage is repaired by the evolutionarily conserved base excision repair (BER) system. Exposure of mice to ionizing radiation affects neurogenesis and neuroinflammation. However, the consequences of deficient DNA repair on adult neurogenesis and neuroinflammation are poorly understood despite their potential relevance for homeostasis. We previously reported that loss of NEIL1, an important DNA glycosylase involved in BER, is associated with deficiencies in spatial memory, olfaction, and protection against ischemic stroke in mice. Here, we show that Neil1−/− mice display an anxiety-mediated behavior in the open field test, a deficient recognitive memory in novel object recognition and increased neuroinflammatory response under basal conditions. Further, mice lacking NEIL1 have decreased neurogenesis and deficient resolution of neuroinflammation following gamma irradiation (IR)-induced stress compared to WT mice. Neil1−/− IR-exposed mice also exhibit increased DNA damage and apoptosis in the hippocampus. Interestingly, behavioral tests two weeks after IR showed impaired stress response in the Neil1−/− mice. Our data indicate that NEIL1 plays an important role in adult neurogenesis and in the resolution of neuroinflammation.

AB - Cellular exposure to ionizing radiation leads to oxidatively generated DNA damage, which has been implicated in neurodegenerative diseases. DNA damage is repaired by the evolutionarily conserved base excision repair (BER) system. Exposure of mice to ionizing radiation affects neurogenesis and neuroinflammation. However, the consequences of deficient DNA repair on adult neurogenesis and neuroinflammation are poorly understood despite their potential relevance for homeostasis. We previously reported that loss of NEIL1, an important DNA glycosylase involved in BER, is associated with deficiencies in spatial memory, olfaction, and protection against ischemic stroke in mice. Here, we show that Neil1−/− mice display an anxiety-mediated behavior in the open field test, a deficient recognitive memory in novel object recognition and increased neuroinflammatory response under basal conditions. Further, mice lacking NEIL1 have decreased neurogenesis and deficient resolution of neuroinflammation following gamma irradiation (IR)-induced stress compared to WT mice. Neil1−/− IR-exposed mice also exhibit increased DNA damage and apoptosis in the hippocampus. Interestingly, behavioral tests two weeks after IR showed impaired stress response in the Neil1−/− mice. Our data indicate that NEIL1 plays an important role in adult neurogenesis and in the resolution of neuroinflammation.

KW - DNA damage

KW - DNA microarray

KW - NEIL1

KW - Neurogenesis

KW - Neuroinflammation

U2 - 10.1016/j.freeradbiomed.2019.05.037

DO - 10.1016/j.freeradbiomed.2019.05.037

M3 - Journal article

C2 - 31175982

AN - SCOPUS:85066948569

VL - 141

SP - 47

EP - 58

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -