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- Title
Drp1-Mediated Mitochondrial Abnormalities Link to Synaptic Injury in Diabetes Model.
- Authors
Shengbin Huang; Yongfu Wang; Xueqi Gan; Du Fang; Changjia Zhong; Long Wu; Gang Hu; Sosunov, Alexander A.; McKhann, Guy M.; Haiyang Yu; ShiDu Yan, Shirley
- Abstract
Diabetes has adverse effects on the brain, especially the hippocampus, which is particularly susceptible to synaptic injury and cognitive dysfunction. The underlying mechanisms and strategies to rescue such injury and dysfunction are not well understood. Using a mouse model of type 2 diabetes (db/db mice) and a human neuronal cell line treated with high concentration of glucose, we demonstrate aberrant mitochondrial morphology, reduced ATP production, and impaired activity of complex I. These mitochondrial abnormalities are induced by im-balanced mitochondrial fusion and fission via a glycogen synthase kinase 3β (GSK3β)/dynamin-related protein-1 (Drp1)-dependent mechanism. Modulation of the Drp1 pathway or inhibition of GSK3β activity restores hippocampal long-term potentiation that is impaired in db/db mice. Our results point to a novel role for mitochondria in diabetes-induced synaptic impairment. Exploration of the mechanisms behind diabetes-induced synaptic deficit may provide a novel treatment for mitochondrial and synaptic injury in patients with diabetes.
- Subjects
ANIMAL models of diabetes; LABORATORY mice; TYPE 2 diabetes; HIPPOCAMPUS injuries; CELL lines; MITOCHONDRIAL pathology
- Publication
Diabetes, 2015, Vol 64, Issue 5, p1728
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db14-0758