Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction.
Several previous studies have indicated that diabetic have higher risk of suffering from Alzheimer's disease, which severely induced cognitive dysfunction. However, the underlying molecular mechanism and more details on the cognitive deficits induced by hyperglycemia have not been elucidated. Here in our present study, on the basis of Goto-Kakizaki (GK) rats and streptozotocin (STZ)-induced diabetic model, we detected the variation of dendritic spine density in hippocampus as well as the differential expression of some important signal transduction molecules that were of relevance in learning and memory function. We found that the magnitude of escape latency time was significantly increased in such diabetic animals; the phosphorylated Akt/CREB; SYP and BDNF as well as other downstream molecules in hippocampus neurons were also downregulated in both diabetic groups compared to the normal groups. Thus, all of these data indicate the obstacle of neuronal pathology and the Akt/CREB signaling pathway caused by hyperglycemia that may suppress cognitive behavior, which may provide a novel way for the prevention of diabetic encephalopathy and the cognitive deficits of Alzheimer's disease.
Institute of Medicine, Medical Research Center, Jishou University, Hunan, China.
Qiong
Q
Xiang
Institute of Medicine, Medical Research Center, Jishou University, Hunan, China.
Jie
J
Zhang
Institute of Medicine, Medical Research Center, Jishou University, Hunan, China.
Chun-Yan
CY
Li
Pharmacy of Department, First People's Hospital of Foshan, Guangdong, China.
Yan
Y
Wang
College of Medicine, Jishou University, Hunan, China.
Mao-Jun
MJ
Zeng
College of Medicine, Jishou University, Hunan, China.
Zhi-Xin
ZX
Cai
Institute of Medicine, Medical Research Center, Jishou University, Hunan, China.
Rong-Bo
RB
Tian
Institute of Medicine, Medical Research Center, Jishou University, Hunan, China.
Wei
W
Jia
Institute of Medicine, Medical Research Center, Jishou University, Hunan, China. Electronic address: lxhsurgeon@126.com.
Xian-Hui
XH
Li
D000818:Animals; D001786:Blood Glucose; D002470:Cell Survival; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D049229:Dendritic Spines / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013311:Streptozocin
D001786:Blood Glucose; D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D013311:Streptozocin; D051057:Proto-Oncogene Proteins c-akt
Akt/CREB signal pathway; Alzheimer's disease; Cognitive deficits; Diabetic encephalopathy; Insulin resistance