Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity
C. Culmsee et al., Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity, MOL BRAIN R, 87(2), 2001, pp. 257-262
DNA damage has been documented in neurodegenerative conditions ranging from
Alzheimer's disease to stroke. DNA-dependent protein kinase (DNA-PK) is in
volved in V(D)J recombination and DNA double strand break repair, and may p
lay a role in cell death induced by DNA damage. We now report that cultured
hippocampal neurons from severe combined immunodeficient (scid) mice which
lack DNA-PK activity are hypersensitive to apoptosis induced by exposure t
o topoisomerase inhibitors, amyloid beta peptide (AP) and glutamate. A simi
lar increased vulnerability of hippocampal CAI and CA3 neurons was observed
in adult scid mice after kainate-induced seizures. Our results suggest tha
t DNA-PK activity is important for neuron survival under conditions that ma
y occur in neurological disorders. (C) 2001 Elsevier Science B.V. All right
s reserved.