Influence of nefiracetam on NGF-induced neuritogenesis and neural cell adhesion molecule polysialic acid expression: in vivo and in vitro comparisons.

Previously, the ability of co-administered nefiracetam to reverse scopolamine-induced learning deficits has been attributed to the preservation of a transient increase in neural cell adhesion molecule (NCAM) polysialylation state during a late phase of memory consolidation (Doyle et al., J. Neurosci. Res., 31 (1992) 513-523). Using the PC-12 pheochromocytoma cell model, we now demonstrate nefiracetam pre-exposure to significantly enhance nerve growth factor-induced neuritogenesis and NCAM polysialylation, but not prevalence, in a dose-dependent manner with maximal effects being observed at the lowest dose (0.1 microM) examined. As the memory-associated increase in NCAM polysialylation in vivo is associated with a defined group of neurons at the dentate hilar/granule cell layer border (Regan and Fox, Neurochem. Res., 20 (1995) 521-526), the effect of chronic nefiracetam exposure in vivo was evaluated. Once-daily, intraperitoneal administration of either 3 or 9 mg/kg nefiracetam to adult male Wistar rats for 40 days significantly increased the number of hippocampal dentate polysialylated neurons only at the highest dose evaluated, suggesting it to prevent their age-dependent decline. These results are consistent with nefiracetam facilitating early induction events of long-term memory consolidation processes involving NCAM polysialylation state.