Staurosporine but not chelerythrine inhibits regeneration in hippocampal organotypic cultures.
A mechanical lesion in hippocampal organotypic cultures is followed by a recovery process involving scar formation, sprouting of fibres and formation of new functional synapses. Here we tested the effect of staurosporine and chelerythrine, two protein kinase C (PKC) inhibitors, on this lesion-induced neurite outgrowth of Shaffer collaterals. At a concentration of 1 microM, staurosporine delayed functional recovery assessed by measuring synaptic field potentials across the lesion, without altering synaptic transmission on nonlesioned cultures. Immunostaining carried out by using antibodies directed against neurofilament proteins showed that there was a marked reduction in the number of regenerating fibres crossing the lesion. In contrast to this, chelerythrine (50 microM) did not prevent functional recovery, although it affected synaptic transmission and plasticity at this concentration. We conclude that the inhibition of sprouting produced by staurosporine is independent of its blockade of PKC-mediated phosphorylation mechanisms.
Toni
N
N
Department of Pharmacology, Centre Médical Universitaire, Geneva, Switzerland.
Stoppini
L
L
Muller
D
D
D000470:Alkaloids; D000818:Animals; D000831:Animals, Newborn; D053119:Benzophenanthridines; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects; D009924:Organ Culture Techniques; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine