Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-ß.
Nat Neurosci
; 16(5): 613-21, 2013 May.
Article
in En
| MEDLINE
| ID: mdl-23525040
ABSTRACT
We show that a natural behavior, exploration of a novel environment, causes DNA double-strand breaks (DSBs) in neurons of young adult wild-type mice. DSBs occurred in multiple brain regions, were most abundant in the dentate gyrus, which is involved in learning and memory, and were repaired within 24 h. Increasing neuronal activity by sensory or optogenetic stimulation increased neuronal DSBs in relevant but not irrelevant networks. Mice transgenic for human amyloid precursor protein (hAPP), which simulate key aspects of Alzheimer's disease, had increased neuronal DSBs at baseline and more severe and prolonged DSBs after exploration. Interventions that suppress aberrant neuronal activity and improve learning and memory in hAPP mice normalized their levels of DSBs. Blocking extrasynaptic NMDA-type glutamate receptors prevented amyloid-ß (Aß)-induced DSBs in neuronal cultures. Thus, transient increases in neuronal DSBs occur as a result of physiological brain activity, and Aß exacerbates DNA damage, most likely by eliciting synaptic dysfunction.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
DNA Breaks, Double-Stranded
/
Neurons
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
2013
Document type:
Article
Affiliation country:
United States