Endonuclease VIII-like 1 (NEIL1) promotes short-term spatial memory retention and protects from ischemic stroke-induced brain dysfunction and death in mice

Chandrika Canugovi, Jeong Seon Yoon, Neil H. Feldman, Deborah L. Croteau, Mark P. Mattson, Vilhelm A. Bohr

Research output: Contribution to journalArticlepeer-review

Abstract

Recent findings suggest that neurons can efficiently repair oxidatively damaged DNA, and that both DNA damage and repair are enhanced by activation of excitatory glutamate receptors. However, in pathological conditions such as ischemic stroke, excessive DNA damage can trigger the death of neurons. Oxidative DNA damage is mainly repaired by base excision repair (BER), a process initiated by DNA glycosylases that recognize and remove damaged DNA bases. Endonuclease VIII-like 1 (NEIL1) is a DNA glycosylase that recognizes a broad range of oxidative lesions. Here, we show that mice lacking NEIL1 exhibit impaired memory retention in a water maze test, but no abnormalities in tests of motor performance, anxiety, or fear conditioning. NEIL1 deficiency results in increased brain damage and a defective functional outcome in a focal ischemia/reperfusion model of stroke. The incision capacity ona 5-hydroxyuracil-containing bubble substrate was lower in the ipsilateral side of ischemic brains and in the mitochondrial lysates of unstressed old NEIL1-deficient mice. These results indicate that NEIL1 plays an important role in learning and memory and in protection of neurons against ischemic injury.

Original languageEnglish (US)
Pages (from-to)14948-14953
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number37
DOIs
StatePublished - Sep 11 2012
Externally publishedYes

ASJC Scopus subject areas

  • General

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