A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat

Abstract

Parkinson's disease (PD) is a progressive neuropathology characterized by motor and non-motor alterations. β-sitosterol β-d-glucoside (BSSG) is a neurotoxin whose prolonged oral administration in rats has been proposed as a new PD model. Herein, we demonstrate that a single, unilateral, and intranigral administration of BSSG also elicits bilateral sensorimotor alterations in the rat. Six behavioral tests evaluated the effect of different concentrations of BSSG (3, 6, 9, and 12 μg/μL DMSO) from 15 to 120 days after administration. The first behavioral alterations, which appeared on day 15, were unbalanced and uncoordinated gaits and a decrease in the sensorimotor cortex activity, as evidenced by the beam-walking and the vibrissae tests, respectively. After 30 days, the corridor test revealed hyposmia and a decreased locomotor activity in the open field. The last alteration was a depressive-like behavior, as shown by the forced swim test on days 60 and 120. According to the cylinder test, no locomotor asymmetry was observed over time with any BSSG concentrations tested. Also, a mesencephalic TH(+) cell loss (p < 0.05) was shown on day 30 when compared with the mock condition, and such a loss was even higher on day 120. At this time, the presence of pathological α-synuclein aggregates in the mesencephalon was documented. Our results show that the stereotaxic intranigral administration of BSSG reproduces some characteristics of oral administration, such as the progression of behavioral alterations, dopaminergic neurons loss, and the presence of Lewy body-like synuclein aggregations, in less time and resources.