NEIL1 stimulates neurogenesis and suppresses neuroinflammation after stress

Beimeng Yang, David M. Figueroa, Yujun Hou, Mansi Babbar, Stephanie L. Baringer, Deborah L. Croteau, Vilhelm A. Bohr*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalFree Radical Biology and Medicine
Volume141
Pages (from-to)47-58
Number of pages12
ISSN0891-5849
DOIs
Publication statusPublished - 2019

Keywords

  • DNA damage
  • DNA microarray
  • NEIL1
  • Neurogenesis
  • Neuroinflammation

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