http://www.pnas.org/content/early/2012/08/22/1204156109.short
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 on a 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.
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