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 incraeses the DNA damage and repair. Specifically, Glutamate, the most abundant neurotransmitter directly stimulates DNA repair in a pathway that we are currently exploring. This raises the possibility that a connection exists between DNA repair and learning.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000723-02
Application #
7964023
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$258,194
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Hou, Yujun; Lautrup, Sofie; Cordonnier, Stephanie et al. (2018) NAD+ supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci U S A 115:E1876-E1885
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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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