Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats.
Diabetes mellitus (DM) may give rise to cognitive impairment, but the pathological mechanism involved was still unknown. We employed streptozotocin (STZ)-induced diabetic rats and test their capacity for learning and memory by three-arm radial maze. We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry. MKP-1 mRNA level in the CA1 and dentate gyrus (DG) Hippocampal area is further determined by RT-PCR method. We also observed the ultrastructures of Hippocampal neurons by transmission electron microscopy (TEM). All data were analyzed by the independent samples t-test. Four weeks after STZ induction, the diabetic rats showed decreased capacity for learning and memory as indicated by the increase in the error number and reaction time in three-arm radial maze test. TEM results showed the ultrastructures of diabetic hippocampus, including area CA1 and DG, neurons were characterized by swollen mitochondria, increased heterochromatin accumulation and reduced synaptic contacts. The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01). RT-PCR results also showed MKP-1 mRNA in the CA1 and DG Hippocampal area was decreased in the diabetic rats. These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition. As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.
Zhou
Jianwei
J
The Second Affiliated Hospital of School of Medicine Zhejiang University, Hangzhou, 310003, China.
Wang
Lingling
L
Ling
Shucai
S
Zhang
Xiaoming
X
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D054638:Dual Specificity Phosphatase 1; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007859:Learning Disabilities / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology
D018797:Cell Cycle Proteins; D019922:GAP-43 Protein; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases