Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice

摘要: Background: The C-terminal domain of the heavy chain tetanus toxin (Hc-TeTx) is a non-toxic peptide with demonstrated in vitro and vivo neuroprotective effects against striatal dopaminergic damage induced by MPP+ (1-methyl-4-phenylpyridinium) 6-hydoxydopamine, suggesting its possible therapeutic potential Parkinson’s disease. Methamphetamine (METH), widely abused psychostimulant, has selective neurotoxicity rodents, monkeys humans. This study was undertaken to determine whether Hc-TeTx might also protect METH-induced consequent motor impairment. Methods: For this purpose, we treated mice toxic regimen METH (4 mg/kg, 3 consecutive i.p. injections, 3h apart) followed injections 40 ug/kg into grastrocnemius muscle at 1h, 24h 48h post treatment. Results: We found that significantly reduced loss markers tyrosine hydroxylase (TH) dopamine transporter (DAT) increases silver staining (a well stablished degeneration marker) striatum. Moreover, prevented increase neuronal nitric oxide synthase (nNOS), but did not affect microglia activation METH. Stereological count substantia nigra indicated TH-positive neurons after partially Hc-TeTx. Importantly, impairment behaviors treatment, were Hc-TeTx. Conclusions: Here demonstrate can provide significant protection acute METH-abusers.