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

Luis O. Soto-Rojas, Linda Garces-Ramirez, Claudia Luna-Herrera, Yazmin M. Flores-Martinez, Guadalupe Soto-Rodriguez, Bismark Gatica-Garcia, Francisco E. Lopez-Salas, José Ayala-Davila, Maria E. Gutierrez-Castillo, America Padilla-Viveros, Cecilia Bañuelos, Fidel de la Cruz-Lopez, Irma A. Martinez-Davila, Daniel Martinez-Fong

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number112279
JournalBehavioural Brain Research
Volume378
DOIs
StatePublished - 27 Jan 2020

Fingerprint

Glucosides
Synucleins
Oral Administration
Parkinson Disease
Lewy Bodies
Vibrissae
Dopaminergic Neurons
Neurotoxins
Locomotion
Mesencephalon
Dimethyl Sulfoxide
Gait
Walking
gamma-sitosterol

Keywords

  • Bilateral lesion
  • BSSG
  • Depression
  • Hyposmia
  • Locomotor activity
  • Parkinson's disease

Cite this

Soto-Rojas, L. O., Garces-Ramirez, L., Luna-Herrera, C., Flores-Martinez, Y. M., Soto-Rodriguez, G., Gatica-Garcia, B., ... Martinez-Fong, D. (2020). A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat. Behavioural Brain Research, 378, [112279]. https://doi.org/10.1016/j.bbr.2019.112279
Soto-Rojas, Luis O. ; Garces-Ramirez, Linda ; Luna-Herrera, Claudia ; Flores-Martinez, Yazmin M. ; Soto-Rodriguez, Guadalupe ; Gatica-Garcia, Bismark ; Lopez-Salas, Francisco E. ; Ayala-Davila, José ; Gutierrez-Castillo, Maria E. ; Padilla-Viveros, America ; Bañuelos, Cecilia ; de la Cruz-Lopez, Fidel ; Martinez-Davila, Irma A. ; Martinez-Fong, Daniel. / A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat. In: Behavioural Brain Research. 2020 ; Vol. 378.
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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.",
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Soto-Rojas, LO, Garces-Ramirez, L, Luna-Herrera, C, Flores-Martinez, YM, Soto-Rodriguez, G, Gatica-Garcia, B, Lopez-Salas, FE, Ayala-Davila, J, Gutierrez-Castillo, ME, Padilla-Viveros, A, Bañuelos, C, de la Cruz-Lopez, F, Martinez-Davila, IA & Martinez-Fong, D 2020, 'A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat', Behavioural Brain Research, vol. 378, 112279. https://doi.org/10.1016/j.bbr.2019.112279

A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat. / Soto-Rojas, Luis O.; Garces-Ramirez, Linda; Luna-Herrera, Claudia; Flores-Martinez, Yazmin M.; Soto-Rodriguez, Guadalupe; Gatica-Garcia, Bismark; Lopez-Salas, Francisco E.; Ayala-Davila, José; Gutierrez-Castillo, Maria E.; Padilla-Viveros, America; Bañuelos, Cecilia; de la Cruz-Lopez, Fidel; Martinez-Davila, Irma A.; Martinez-Fong, Daniel.

In: Behavioural Brain Research, Vol. 378, 112279, 27.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat

AU - Soto-Rojas, Luis O.

AU - Garces-Ramirez, Linda

AU - Luna-Herrera, Claudia

AU - Flores-Martinez, Yazmin M.

AU - Soto-Rodriguez, Guadalupe

AU - Gatica-Garcia, Bismark

AU - Lopez-Salas, Francisco E.

AU - Ayala-Davila, José

AU - Gutierrez-Castillo, Maria E.

AU - Padilla-Viveros, America

AU - Bañuelos, Cecilia

AU - de la Cruz-Lopez, Fidel

AU - Martinez-Davila, Irma A.

AU - Martinez-Fong, Daniel

PY - 2020/1/27

Y1 - 2020/1/27

N2 - 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.

AB - 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.

KW - Bilateral lesion

KW - BSSG

KW - Depression

KW - Hyposmia

KW - Locomotor activity

KW - Parkinson's disease

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U2 - 10.1016/j.bbr.2019.112279

DO - 10.1016/j.bbr.2019.112279

M3 - Artículo

C2 - 31606429

AN - SCOPUS:85075427038

VL - 378

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

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