Abstract: Objective To observe morphological changes in the nigrostriatal pathway by progress of parkinsonism in a mouse model, in order to investigate the pathophysiology of Parkinson’s disease from different contexts and to provide some new clues for Parkinson’s prevention, delay, and treatment.Methods Thirty-six C57 mice were randomly divided into the saline control and the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection groups, with eighteen mice per group. The number of dopaminergic neurons in the substantia nigra, their nerve fiber densities and distributions on the striatal neurons with the direct and indirect pathway cells (dopamine D1 receptors/dopamine D2 receptors positive, D1R/D2R positive) in the striatum were observed by immunohistochemistry and confocal microscopy at 7, 14, 21, 25, 28 and 35 days after the injection.Results The number of dopaminergic neurons reduced to 40%-50% in the substantia nigra after injection of MPTP. Compared with the control, the decrease of dopaminergic fibers in the striatum showed a tendency that had an early reduction followed by an increase, with a minimum at day 21 (loss of 20% fibers), and reaching 45% fibers at the 35th day after injection. The distribution ratio of the dopaminergic terminals on striatal neurons to D1R/D2R positive cells was relatively low at day 21, and reached a peak on the day 35.Conclusion The dopaminergic fibers in the striatum show a significant regeneration after a MPTP lesion of the substantia nigra, and these regenerated fibers distribute mostly on those neurons in the direct pathway. The balance of dopamine’s activity regulation on the direct and indirect pathways of basal ganglia is broken. This may be an importa

Key words: P>Parkinson’s disease, Dopaminergic neuron, Nerve fiber, Dopamine receptor, Immunohistochemistry, Immunofluorescence, Mouse/P>