Brain Alterations Linked to the MPTP Mouse Model of Parkinson's Disease Uncovered by Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy.

Abstract

AIMS: This study employed diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (H-MRS) on an MPTP-induced mouse model of Parkinson's disease (PD) to examine microstructural changes linked to neuroinflammation and neurodegeneration. METHODS: MPTP (20 mg/kg, i.p.) was given for 4 days, and behavioral assessment, MRI imaging, and immunohistochemistry were performed at 24 h and 72 h after last MPTP treatment. RESULTS: At 24 h, DKI showed higher diffusivity metrics in the hippocampus and thalamus, whileH-MRS identified reduced Glu/tCr and Glx/tCr ratios in the striatum of MPTP-treated mice compared to saline-treated mice. Behavioral tests at 72 h revealed motor impairment and DKI showed increased diffusivity in the somatosensory cortex, thalamus, and striatum in MPTP-treated mice. Notably, at 72 h, the hippocampus showed partial recovery in diffusivity, suggesting adaptive changes or partial restoration. Higher diffusivity was observed in the cortex, striatum, and thalamus in MPTP-treated mice. Furthermore,H-MRS detected a higher Tau/tCr in the striatum, while in the hippocampus, lower Gln/tCr and NAA/tCr and higher Cho/NAA were observed at 72 h in MPTP-treated mice, indicating persistent neuronal death and membrane deterioration. Immunofluorescence staining at 72 h confirmed these findings, showing a decrease in NeuN+ neurons and an increase in GFAP+ glial cells in the striatum and hippocampus, indicating neurodegeneration and gliosis. Additionally, MPTP caused a loss of dopaminergic neurons in the substantia nigra and striatum, which likely explains the higher diffusivity shown by DKI. CONCLUSION: These findings demonstrate DKI andH-MRS are sensitive, non-invasive modalities for detecting and monitoring neurodegenerative microstructural and neurochemical changes, enhancing the understanding of PD-related pathology and progression.