Open AccessThe Disturbance of Hippocampal C a MKII / PKA / PKC Phosphorylation in Early Experimental Diabetes Mellitus
Author(s) -
Liao MeiHua,
Xiang YingChun,
Huang JiYun,
Tao RongRong,
Tian Yun,
Ye WeiFeng,
Zhang GenSheng,
Lu YingMei,
Ahmed Muhammad M.,
Liu ZhiRong,
Fukunaga Kohji,
Han Feng
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12084
Subject(s) - medicine , endocrinology , synapsin i , phosphorylation , protein kinase c , protein kinase a , streptozotocin , diabetes mellitus , kinase , hippocampal formation , hippocampus , type 2 diabetes , calmodulin , chemistry , biochemistry , calcium , vesicle , membrane , synaptic vesicle
Summary Background Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes. Aims To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats. Methods Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry. Results Our data showed a pronounced decrease in the phosphorylation of Ca 2+ /calmodulin‐dependent protein kinase II (Ca MKII ) in the hippocampi of both type 1 and type 2 diabetic rats compared with age‐matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I ( S er 603) and G lu R 1 ( S er 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C ( PKC ) and protein kinase A ( PKA ) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP 1α and PP 2 A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up‐regulated in type 2 diabetic rats. Conclusions The disturbance of Ca MKII / PKA / PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes‐related cognitive dysfunction.