Striatal injection of aminochrome in Wistar rats induces early-stage behavioral changes of Parkinson's disease and dopaminergic degeneration in the caudal and medial regions of the nigra pars compacta.

Most preclinical Parkinson's disease (PD) models use neurotoxic agents to cause rapid dopaminergic neuron degeneration, mimicking the late stage of PD. That creates a gap in understanding early-stage pathophysiology, critical for neuroprotective therapies and early diagnosis. To replicate the prodromal stage of PD, it is pivotal that preclinical study models promote a slow and selective death of dopaminergic neurons, triggering degenerative processes and early symptoms. In this context, we investigated behavioral and neuronal changes using a model of unilateral aminochrome injection (6 nmol/6 μL) in the striatum of adult male Wistar rats (CEUA-ICS, Protocol 3006070223), focusing on subtle changes representative of the early stages of PD. On the fourteenth day after the stereotaxic injection, we observed behavioral impairments marked by a reduction of frequency of entries, time spent and distance traveled in the central quadrants in the open field test, reduction of frequency of rearing and grooming in the open field, as well as an increase in the rate of motor asymmetry in the cylinder test. In addition, we observed a decrease in the transition of animals through the elevated plus maze, with a reduction in the number of entries into the open arm. Immunohistochemical analyses indicated that aminochrome induces cytotoxicity for tyrosine hydroxylase-positive (TH+) cells and induces astrogliosis and microgliosis. Our findings show that striatal injection of aminochrome induces a reduction in the density of TH+ fibers in the striatum, a slight reduction in the number of dopaminergic neurons in the caudal and medial regions of the nigra pars compacta (SNpc), and subtle motor deficits typical of an early stage of PD. Here, we provided evidence that aminochrome can induce a rodent model of the prodromal stages of PD.