Reduced basal CaMKII levels in hippocampal CA1 region: possible cause of stress-induced impairment of LTP in chronically stressed rats. Hippocampus 2004;14(3):402-10
Date
05/11/2004Pubmed ID
15132438DOI
10.1002/hipo.10193Scopus ID
2-s2.0-2342561035 (requires institutional sign-in at Scopus site) 87 CitationsAbstract
Chronic psychosocial stress markedly reduces the expression of high-frequency stimulation (HFS)-evoked early long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Immunoblotting was performed to determine changes in molecular levels of key signaling proteins that might be responsible for this inhibitory effect. Western blot analysis of the CA1 region demonstrates that chronic psychosocial stress decreases basal levels of calcium calmodulin kinase II (CaMKII), phosphorylated (P)-CaMKII, calmodulin, and protein kinase C (PKCgamma) while markedly increasing protein phosphatase 2B (calcineurin) levels. The decrease of basal levels of P-CaMKII may be triggered primarily by excessive dephosphorylation resulting from enhanced basal levels of calcineurin. The decline in the basal levels of the upstream molecules, PKCgamma and calmodulin may be a consequence of the diminished basal P-CaMKII levels. Analysis of signaling molecules in CA1 region of chronically stressed rat subjected to HFS in vivo showed only one difference compared to similarly stimulated control rats; no increase in P-CaMKII levels. Our results suggest that decreased P-CaMKII levels may be primarily responsible for the stress-induced reduction in LTP expression.
Author List
Gerges NZ, Aleisa AM, Schwarz LA, Alkadhi KAAuthor
Nashaat Gerges PhD Chair, Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcineurin
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin
Chronic Disease
Down-Regulation
Hippocampus
Long-Term Potentiation
Male
Memory Disorders
Phosphorylation
Protein Kinase C
Rats
Rats, Wistar
Signal Transduction
Stress, Psychological