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.
Odumeru
O
O
Department of Pharmacology, University College Dublin, Ireland.
Murphy
K J
KJ
O'Connell
A W
AW
Regan
C M
CM
Shiotani
T
T
D000375:Aging / Q000523:psychology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016716:PC12 Cells; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000096:biosynthesis*
D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; D018697:Nootropic Agents; D011760:Pyrrolidinones; D012794:Sialic Acids; C058876:nefiracetam