MRI reveals cerebral iron, calcification and spinal cord atrophy in M83 mouse model of Parkinson’s disease

Abstract

AbstractBackgroundRodent models of Parkinson’s disease have been crucial tools for understanding the pathogenic mechanisms of alpha‐synuclein‐associated alterations. Here, we employed multiparametric high‐field magnetic resonance imaging (MRI) to examine the molecular alterations and neurodegeneration in the brain and spinal cord of transgenic M83 (A53T) murine model of Parkinson’s disease.MethodTen nontransgenic littermates and twelve M83 mice at 10‐11 months of age were assessed. Gradient echo MR for susceptibility‐weighted imaging (SWI) and T1 MR scans were acquired ex vivo at 9.4 T in the brain and spinal cord of mice. Histology and immunofluorescence staining for alpha‐synuclein inclusions (phospho‐S129), NeuN, GFAP and Iba‐1 for gliosis were used to investigate the nature of the imaging observations.ResultFrom T1 MR, a reduced area of white matter in the thoracic spinal cord (T1) and a reduced area of gray matter in the cervical (C6‐C8) and thoracic (T1) spinal cord were observed in the M83 mice compared to nontransgenic mice. In addition, lower left‐right length measurements in the cervical (C8) spinal cord were observed in M83 mice than in nontransgenic mice. SW images revealed regional hypointensities in the hippocampus, cortex, striatum, midbrain and thalamus of M83 mice, which in corresponding phase images indicated both diamagnetic (calcification) and paramagnetic (iron) lesions in the brains of M83 mice. Immunofluorescence staining demonstrated an increased Iba‐1 level in the brains of M83 mice, indicating microgliosis.ConclusionWe found cerebral iron, calcification, microgliosis and spinal cord atrophy in M83 mice.