Manganese-Enhanced Magnetic Resonance Imaging Detects Vipr2-Mediated Immune Transformation in A Model of Parkinson'S Disease

Abstract Progressive nigrostriatal degeneration and neuroinflammation underlie the pathobiology of Parkinson’s disease (PD). Biomarkers to detect such pathogenic events remain in development. We report that manganese-enhanced magnetic resonance imaging (MEMRI) can be used to assess inflammatory activities related to deficits in neural connectivity in an experimental PD model. Vasoactive intestinal peptide (VIP), an endogenous neuropeptide that binds to VIPR1 and VIPR2 inducing a phenotypic shift of neurotoxic effector memory to neuroprotective regulatory T cells was modified (referred to as LBT-3627) to improve its half-life and limit proteolytic cleavage. LBT-3627 was used to investigate its ability to elicit neuroprotection in mice treated with the nigrostriatal toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with LBT-3627 lead to neuronal sparing when compared to MPTP-treated mice. Seven days post MPTP intoxication, mice were scanned using MEMRI, and images were registered to an MEMRI-based brain atlas for comparison. Manganese-induced MRI signal enhancement was calculated. MEMRI detected MPTP-induced inflammation as well as a corresponding reduction in signal with low and high doses of LBT-3627. MPTP-treated mice showed a significantly higher signal enhancement within the hippocampus (p = 0.04), with a trend towards significance in both the substantia nigra and striatum when compared to saline controls. The higher signal enhancement was reversed by LBT-3627 treatment. These findings indicate the ability of MEMRI to detect MPTP-induced brain pathology and its reversal following LBT-3627 treatment, supporting MEMRI as a method to assess changes in nigrostriatal-induced neuroinflammation.