Comparison between 2‐day and 10‐day MPTP treatment modalities in the mouse model of Parkinson's disease

Abstract We employed a novel regimen of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) treatment to produce a Parkinson's disease (PD) animal model demonstrating typical Parkinsonian symptoms. In order to compare the effects of the different durations of MPTP treatment (daily intraperitoneal injections of 30 mg/kg MPTP for 2 or 10 days), the numbers and distribution patterns of tyrosine hydroxylase‐immunoreactive (TH‐ir) neurons and fibers were examined in the substantia nigral and stiatal brain regions of C57/B16 mice. The mean numbers of TH‐ir neurons in the substantia nigra were significantly lower (57.3% and 48.1%) than the numbers in the saline‐treated controls after 2 and 10 days of MPTP treatment, respectively. Furthermore, the optical density of the TH‐ir fibers in the striatum was reduced by 9.8% and 14.1% after 2‐ and 10‐day treatments, respectively. However, the reduction in numbers of TH‐ir neurons in the substantia nigra and striatum was not significantly different between the 2‐day and 10‐day treatment groups. Yet, it seems that only the 10‐day treatment regimen exceeded the threshold of motor deficits. Thus, chronic MPTP treatment appears to be required to mirror the pathophysiological characteristics of Parkinsonism.