Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity

Carsten Culmsee, Subbarao Bondada, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

DNA damage has been documented in neurodegenerative conditions ranging from Alzheimer's disease to stroke. DNA-dependent protein kinase (DNA-PK) is involved in V(D)J recombination and DNA double strand break repair, and may play 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 to topoisomerase inhibitors, amyloid beta peptide (Aβ) and glutamate. A similar increased vulnerability of hippocampal CA1 and CA3 neurons was observed in adult scid mice after kainate-induced seizures. Our results suggest that DNA-PK activity is important for neuron survival under conditions that may occur in neurological disorders.

Original languageEnglish (US)
Pages (from-to)257-262
Number of pages6
JournalMolecular Brain Research
Volume87
Issue number2
DOIs
StatePublished - Mar 5 2001

Keywords

  • Alzheimer's disease
  • Amyloid beta-peptide
  • DNA repair
  • Epileptic seizure
  • Glutamate
  • Topoisomerase inhibitor

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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