title: The changes of signal transduction pathways in hippocampal regions and postsynaptic densities after chronic cerebral hypoperfusion in rats.
abstract: The mechanisms underlying the cognitive impairment after chronic cerebral hypoperfusion (CCH) are not fully clarified. In the present study, we investigated the molecular basis for the cognitive deficits under the condition of CCH in rats. The ultrastructural changes of postsynaptic densities (PSDs) were examined by ethanolic phosphotungstic acid (EPTA) electron microscopy. Various protein kinase phosphorylation/dephosphorylation levels of the signal transduction pathways in hippocampal regions and postsynaptic densities were assessed by Western blotting. On EPTA electron microscopy, we demonstrated that proteins were highly aggregated in PSD structures of the hippocampal CA1 areas in rats at 3 months after CCH. By Western blotting, the model rats exhibited significant decrease in the levels of hippocampal Ca(2+)-calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), phospho-extracellular regulated kinase (p-ERK), PSD CaMKII and p-ERK, with no corresponding changes in the levels of phosphorylation/dephoosphorylation protein kinase A (PKA) and protein kinase C (PKC). These results suggest that both the ultrastructural changes of PSDs and aberrant signal transduction may be involved in CCH-induced alterations in synaptic transmission underlying the cognitive dysfunction in rats of CCH.
authors: Department of Neurosurgery, Tongji Hospital, Tongji University, Shanghai 200065, PR China. haijiandoc@yahoo.com.cn
authors: Jian
authors: J
authors: Hai
authors: Fei
authors: F
authors: Yu
authors: Qi
authors: Q
authors: Lin
authors: Shao-Hua
authors: SH
authors: Su
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000201:enzymology / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D006624:Hippocampus / Q000201:enzymology / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation; D057907:Post-Synaptic Density / Q000648:ultrastructure*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011494:Protein Kinases