title: Contribution of single-minded 2 to hyperglycaemia-induced neurotoxicity.
abstract: Diabetes mellitus is associated to central nervous system damage, which results in impairment of brain functions and cognitive deficits and decline in memory. However, the mechanisms mediating the actions of glucose on the neurons remained elusive. Single-minded 2 (Sim2), a basic helix-loop-helix (bHLH)-PAS transcriptional repressor, is thought to be involved in some symptoms of Down syndrome. We hypothesized that Sim2 mediated hyperglycaemia-induced neuronal injury and impairment of learning and memory. It was found that expression of Sim2 protein in cortical neurons was increased in streptozotocin-induced diabetes mellitus rat model. Drebrin, down-regulated by Sim2, was subsequently decreased as detected by confocal laser scanning microscopy and Western blot analysis. The expression pattern of Sim2 and Drebrin correspond to 50mmol/L glucose (hyperglycaemia) was also found in primary cultured neurons. Curcumin, one neuroprotective agent, inhibited hyperglycaemia-induced neurotoxicity. Moreover, curcumin alleviated Sim2 expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia. Finally, we found that silencing Sim2 expression decreased hyperglycaemia-induced neuronal injury. In conclusion, Sim2 may mediate neurotoxicity during hyperglycaemia and thereby play a critical role in the development of hyperglycaemia-induced cognitive deficits.
authors: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xiaolan
authors: X
authors: Wang
authors: Yi
authors: Y
authors: Song
authors: Lu
authors: L
authors: Chen
authors: Guobing
authors: G
authors: Zhuang
authors: Jing
authors: J
authors: Zhang
authors: Man
authors: M
authors: Li
authors: Xian-Fang
authors: XF
authors: Meng
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D003474:Curcumin; D009479:Neuropeptides; D018696:Neuroprotective Agents; C583323:Sim2 protein, rat; C053386:drebrins