Effects of a phorbol ester and cyclosporin A on hippocampal synaptic plasticity in streptozotocin-induced-diabetic rats: reduced sensitivity to phorbol esters

Abstract

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 4β-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.