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

Unilateral intranigral administration of β-sitosterol β-D-glucoside triggers pathological α-synuclein spreading and bilateral nigrostriatal dopaminergic neurodegeneration in the rat

“…Also, the chronic administration replicates the sequence in which pathological α-synuclein appears in several brain nuclei, according to the Braak stages of PD [78]. Recently, we showed that a single intranigral administration of BSSG reproduces most of the features of oral administration in less time [68]. The key findings relevant for PD were the progression of motor and non-motor alterations and the loss of dopaminergic neurons, as well as the bilateral presence of Lewy body-like synuclein aggregates in the SNpc [68].…”

“…Animals were kept under inverted light-dark 12 h cycles, 22 ± 2°C and 60 ± 5% humidity, with access to food and water ad libitum. Animals were randomly assigned to the BSSG group (n = 48), with a stereotaxic infusion of 6 μg BSSG /1 μL of DMSO [68]; the mock group (stereotaxic injection of 1 μL of DMSO; n = 48); and the untreated (UT) group (no surgery, nor treatment; n = 48). Six rats of each experimental group were evaluated with two independent immunostaining methods (n = 3 rats per each procedure per group) and six rats with Golgi-Cox staining (n = 6 rats per group).…”

“…A trepan was made to infuse 6 μg of BSSG (MedChemExpress; Monmouth Junction, NJ, USA) dissolved in 1 μL of DMSO (Sigma-Aldrich; St. Louis, MO, USA) or only DMSO, through a blunt 20-gauge dental needle in the left SNpc. The coordinates were, AP, + 2.1 mm from interaural midpoint; ML, + 2.0 mm from interparietal suture; DV, − 6.8 mm from dura mater [68]. The infusion was made by a microperfusion pump (Stoelting; Wood Dale, IL, USA) at 0.15 μL/min.…”

“…Recently, we showed that a single intranigral administration of BSSG reproduces most of the features of oral administration in less time [68]. The key findings relevant for PD were the progression of motor and non-motor alterations and the loss of dopaminergic neurons, as well as the bilateral presence of Lewy body-like synuclein aggregates in the SNpc [68]. Herein, we aim at demonstrating that a single administration of BSSG (6 μg/μL DMSO) in the left SNpc causes the spread of α-synucleinopathy and bilateral neurodegeneration of the nigrostriatal dopaminergic system [68].…”

“…The key findings relevant for PD were the progression of motor and non-motor alterations and the loss of dopaminergic neurons, as well as the bilateral presence of Lewy body-like synuclein aggregates in the SNpc [68]. Herein, we aim at demonstrating that a single administration of BSSG (6 μg/μL DMSO) in the left SNpc causes the spread of α-synucleinopathy and bilateral neurodegeneration of the nigrostriatal dopaminergic system [68]. We showed pathological α-synuclein aggregates in different brain nuclei by immunohistochemistry.…”