Effects of a phorbol ester and cyclosporin A on hippocampal synaptic plasticity in streptozotocin-induced-diabetic rats: reduced sensitivity to phorbol esters.
In streptozotocin-induced diabetic (STZ-diabetic) rats, an animal model of diabetes mellitus, a reduced expression of long-term potentiation (LTP) and enhanced long-term depression (LTD) are observed. This study examined the role of protein kinase C (PKC) and protein phosphatase 2B in hippocampal synaptic transmission in STZ-diabetic rats. The phorbol ester 4beta-phorbol-12,13-dibutyrate (PDB) induced a concentration-dependent potentiation of synaptic responses in area CA1 that could partially be inhibited by the PKC inhibitor chelerythrine. In slices from STZ-diabetic rats the effectivity of PDB to increase synaptic transmission was reduced compared to slices from control animals. In STZ-diabetic rats the protein phosphatase 2B (PP2B) inhibitor cyclosporin A inhibited LTD induction, but did not affect the induction of LTP. In conclusion, these data show a reduced response to PDB in STZ-diabetic rats, and indicate that the lack of LTP induction in these animals is not due to increased PP2B activity.
Kamal
Amer
A
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, TheNetherlands. a.kamal@med.uu.nl
Ramakers
Geert M J
GM
Biessels
Geert-Jan
GJ
Gispen
Willem Hendrik
WH
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D010617:Phenanthridines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
D000470:Alkaloids; D053119:Benzophenanthridines; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D015240:Phorbol 12,13-Dibutyrate; D016572:Cyclosporine; C016299:chelerythrine; D011493:Protein Kinase C; D019703:Calcineurin