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

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

  • Behav Brain Res. 2020 Jan 27;378:112279. doi: 10.1016/j.bbr.2019.112279.
Luis O Soto-Rojas 1,  Linda Garces-Ramirez 1,  Claudia Luna-Herrera 1,  Yazmin M Flores-Martinez 2,  Guadalupe Soto-Rodriguez 3,  Bismark Gatica-Garcia 2,  Francisco E Lopez-Salas 4,  José Ayala-Davila 2,  Maria E Gutierrez-Castillo 5,  America Padilla-Viveros 6,  Cecilia Bañuelos 6,  Fidel de la Cruz-Lopez 1,  Irma A Martinez-Davila 2,  Daniel Martinez-Fong 7
Affiliations

Affiliations

  • 1 Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu S/N, Unidad Profesional "Adolfo López Mateos", Ciudad de México 07738, México.
  • 2 Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional No. 2508, Ciudad de México 07360, México.
  • 3 Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2702, Puebla 72420, PUE, México.
  • 4 Programa de Doctorado en Nanociencias y Nanotecnología, Av. Instituto Politécnico Nacional No. 2508, Centro de Investigación y de Estudios Avanzados, Ciudad de México 07360, México.
  • 5 Departamento de Biociencias e Ingeniería, Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo, Instituto Politécnico Nacional, 30 de Junio de 1520 s/n, Ciudad de México 07340, México.
  • 6 Coordinación General de Programas Multidisciplinarios. Programa Transdisciplinario en Desarrollo Científico y Tecnológico para la Sociedad. Av. Instituto Politécnico Nacional No. 2508, Centro de Investigación y de Estudios Avanzados, Ciudad de México 07360, México.
  • 7 Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional No. 2508, Ciudad de México 07360, México; Programa de Doctorado en Nanociencias y Nanotecnología, Av. Instituto Politécnico Nacional No. 2508, Centro de Investigación y de Estudios Avanzados, Ciudad de México 07360, México. Electronic address: dmartine@fisio.cinvestav.mx.
PMID: 31606429 DOI: 10.1016/j.bbr.2019.112279
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.

Keywords

BSSG; Bilateral lesion; Depression; Hyposmia; Locomotor activity; Parkinson’s disease.

Figures
Products