Docosahexaenoic acid protection in a rotenone induced Parkinson's model: Prevention of tubulin and synaptophysin loss, but no association with mitochondrial function.

Autor: Serrano-García N; Laboratorio de Neurobiología Molecular y Celular, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg, Tlalpan, CP 14269, Ciudad de México, Mexico; Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Deleg, Iztapalapa, CP 09340, Ciudad de México, Mexico. Electronic address: nasmy_sr@yahoo.com.mx., Fernández-Valverde F; Laboratorio de Patología Experimental, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg, Tlalpan, CP 14269, Ciudad de México, Mexico. Electronic address: fferval@yahoo.com.mx., Luis-Garcia ER; Laboratorio de Biología Celular, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Belisario Domínguez Sección XVI Deleg, Tlalpan, CP 14080, Ciudad de México, Mexico. Electronic address: erikarubi_84@yahoo.com.mx., Granados-Rojas L; Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, Col. Insurgentes Cuicuilco, Deleg, Coyoacán, CP 04530, Ciudad de México, Mexico. Electronic address: lgranados_2000@yahoo.com.mx., Juárez-Zepeda TE; Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, Col. Insurgentes Cuicuilco, Deleg, Coyoacán, CP 04530, Ciudad de México, Mexico. Electronic address: tarsilaejz@gmail.com., Orozco-Suárez SA; Unidad de Investigación Médica en Enfermedades Neurológicas, Centro Médico Nacional 'Siglo XXI' Hospital de Especialidades Dr. Bernardo Sepúlveda Gutiérrez, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Deleg, Cuauhtemoc, CP 06720, Ciudad de México, Mexico. Electronic address: sorozco5@hotmail.com., Pedraza-Chaverri J; Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México. Av. Universidad No. 3000, Deleg, Coyoacán, CP 04510, Ciudad de México, Mexico. Electronic address: pedraza@unam.mx., Orozco-Ibarra M; Laboratorio de Neurobiología Molecular y Celular, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg, Tlalpan, CP 14269, Ciudad de México, Mexico. Electronic address: marisol.orozco.ibarra@gmail.com., Jiménez-Anguiano A; Área de Neurociencias, Departamento de Biología de la Reproducción, Universidad Autónoma Metropolitana-Iztapalapa, México, San Rafael Atlixco No. 186, Col. Vicentina, Deleg, Ztapalapa, CP 09340, Ciudad de México, Mexico. Electronic address: aja@xanum.uam.mx.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2018 Dec; Vol. 121, pp. 26-37. Date of Electronic Publication: 2018 Oct 19.
DOI: 10.1016/j.neuint.2018.10.015
Abstrakt: Rotenone, a classic mitochondrial complex I inhibitor, leads to dopaminergic neuronal death resulting in a Parkinson's-like-disease. Docosahexaenoic acid (DHA) has shown neuroprotective effects in other experimental models of Parkinson's disease, but its effect on the rotenone-induced parkinsonism is still unknown. We tested whether DHA in vivo exerts a neuroprotective effect on rotenone-induced parkinsonism and explored the mechanisms involved, including mitochondrial function and ultrastructure as well as the expression of tubulin and synaptophysin. We pretreated eighty male Wistar rats with DHA (35 mg/kg/day) for seven days and then administered rotenone for eight days. We then measured rearing behavior, number of dopaminergic neurons, tyrosine hydroxylase content, tubulin and synaptophysin expression, mitochondrial complex I, respiratory control ratio, mitochondrial transmembrane potential, ATP production activity and mitochondrial ultrastructure. We found that in vivo DHA supply exerted a neuroprotective effect, evidenced by decreased dopaminergic neuron cell death. Although we detected rotenone induced mitochondrial ultrastructure alterations, these were not associated with mitochondrial dysfunction. Rotenone had no effect on mitochondrial complex I, respiratory control ratio, mitochondrial transmembrane potential or ATP production activity. DHA also prevented a rotenone-induced decrease in tubulin and synaptophysin expression. Our results support the neuroprotective effect of DHA on rotenone-induced parkinsonism, and a possible effect on early stage Parkinson's disease. This protective effect is not associated with mitochondrial function improvement, but rather with preventing loss of tubulin and synaptophysin, proteins relevant to synaptic transmission.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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