DNA repair dysfunction in neurodegeneration

我们研究了单个原代大鼠神经元中的DNA修复。 这些神经元修复多种DNA损伤，尤其是修复紫外线诱导的DNA损伤。这一点很重要，因为紫外线对DNA的损伤是通过称为核苷酸切除修复的DNA修复过程来消除的，而核苷酸切除修复通常被认为是CNS中的缺陷。 我们还发现在分化的神经元中氧化DNA损伤修复的衰减，并且我们发现在氧化应激后突触区域中的DNA修复是相当稳健的。 此外，神经传递和DNA修复之间似乎存在联系，因为神经递质的加入增加了神经元的DNA损伤和修复。具体来说，谷氨酸，最丰富的神经递质直接刺激DNA修复的途径，我们目前正在探索。这提出了DNA修复和学习之间存在联系的可能性。

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.