Current available treatments for Parkinson s Disease (PD) focus on relieving motor and cognitive symptoms and improving quality of life. Animal models are essential to investigate PD aetiology, pathology, and therapeutic approaches. One of the most widely used PD animal models is the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse. Chronic injections with MPTP result in characteristics of PD in these animals including the loss of dopaminergic neurons, and gait and motor abnormalities. Because increased reactive oxidative stress is involved in the MPTP-induced neurotoxicity, the MPTP mouse model was selected with the aim of investigating the efficacy of ROS-redox modulating compound KH176 on behavioural deficits and structural- and functional brain connectivity caused by severe damage of the nigrostriatal dopaminergic system by administration of MPTP. In pursuing this goal, a behavioural, neuroimaging and neurobiological investigation has been carried out. Specifically, after having divided the animals in 4 experimental groups (compound or control diet and MPTP or vehicle injection), baseline and post-MPTP injection/diet treatment behavioural measurements were performed by using open field, rotarod, grip test, gait analysis and fear conditioning. Furthermore, animals were assessed with different brain imaging techniques to investigate brain structure and function, including dopamine transporter nuclear imaging (DAT-SPECT), resting state functional Magnetic Resonance Imaging (fMRI), and Diffusion Tensor Imaging (DTI). Animals were, then, sacrificed and blood plasma and brains were collected for molecular- and biochemical analysis and compound exposure. TH immunostaining was performed to quantify the dopaminergic neurons in the substantia nigra and striatum. This dataset has been converted using BrkRaw (vmri_dho.json)at 2022-05-03 13:25:56.964953. ## How to cite? - https://doi.org/10.5281/zenodo.3818615