Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase

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Abstract
SPECIFIC AIMSThis study determined the neuroprotective effect of dextromethorphan (DM) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). Using wild-type and gene knockout mice, the role of oxygen free radical producing NADPH oxidase in the DM-afforded neuroprotection was examined.PRINCIPAL FINDINGS1. DM protects substantia nigra pars compacta (SNpc) dopaminergic neurons against MPTP-induced degenerationWe used a subchronic dosing regiment of MPTP injections to induce lesions in the nigrostriatal dopaminergic pathway. C57BL/6J mice received daily subcutaneous (s.c.) injections of vehicle or MPTP (15 mg free base/kg body weight) for 6 consecutive days. Six or 21 days later, the mice were killed. We quantified the MPTP-induced loss of SNpc tyrosine hydroxylase-immunoreactive (TH-ir) neurons and the decrease in striatal catecholamine content. To determine the effect of DM on the MPTP-induced dopaminergic neuronal lesions, mice were given twice-daily s.c. injec...