The authors of this paper show that exploration of a novel environment by mice, causes DNA double-strand breaks in multiple brain regions of these animals.  DNA double-strand breaks were most abundant in the dentate gyrus, which is involved in learning and memory, and were repaired within 24 hours. Increasing neuronal activity by sensory or optogenetic stimulation increased neuronal DNA double-strand breaks in relevant but not irrelevant networks.

Mice transgenic for human amyloid precursor protein (hAPP) had increased neuronal DNA double-strand breaks at baseline and more severe and prolonged breaks after exploration. Interventions that suppressed aberrant neuronal activity and improved learning and memory in hAPP mice normalized their levels of DNA double-strand breaks. Blocking extrasynaptic NMDA-type glutamate receptors prevented amyloid-beta-induced DNA double-strand breaks in neuronal cell cultures. The authors suggest that transient increases in neuronal DNA double-strand breaks occur as a result of physiological brain activity, and that amyloid-beta may increase DNA damage via synaptic dysfunction. Amyloid-beta is important for neuronal dysfunction in Alzheimer’s disease.

Suberbielle E, Sanchez PE, Kravitz AV, Wang X, Ho K, Eilertson K, Devidze N, Kreitzer AC, Mucke L: Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid. Nature Neuroscience [ Epub ahead of print, March 24, 2013; doi:10.1038/nn.3356 ].

http://www.ncbi.nlm.nih.gov/pubmed/23525040

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