We have studied DNA repair in individual primary rat neurons. These neurons repair many kinds of DNA damage, and it is particularly novel that they repair UV induced DNA damage. This is important because UV damage to DNA is removed by the DNA repair process called nucleotide excision repair, which is generally thought to be deficient in the CNS. We also find attenuation of oxidative DNA damage repair in differentiating neurons and we find that the DNA repair in the synaptic region is quite robust after oxidative stress. Furthermore, there seems to be a connection between neurotransmission and DNA repair because the addition of neurotransmitters to neurons increases DNA damage and repair. Specifically, we observed that at non-toxic physiological levels of glutamate, it induced DNA damage and this damage was dependent upon calcium and mitochondrial ROS because calcium chelators and mitochondrial inhibitors prevented the DNA damage. We further showed that the glutamate-induced DNA damage induced APE1 mRNA and that APE1 is a key player in the repair of glutamate-induced DNA damage. The APE1 induction was shown to be dependent on signaling through a calcium and CREB-mediated pathway. Given that glutamate is the most abundant neurotransmitter, this raises the notion that there exists a connection between DNA repair, memory and learning.
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| Hou, Yujun; Song, Hyundong; Croteau, Deborah L et al. (2017) Genome instability in Alzheimer disease. Mech Ageing Dev 161:83-94 |
| Karikkineth, Ajoy C; Scheibye-Knudsen, Morten; Fivenson, Elayne et al. (2017) Cockayne syndrome: Clinical features, model systems and pathways. Ageing Res Rev 33:3-17 |
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| Fivenson, Elayne M; Lautrup, Sofie; Sun, Nuo et al. (2017) Mitophagy in neurodegeneration and aging. Neurochem Int 109:202-209 |
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