Striatal mitochondria response to 3-nitropropionic acid and fish oil treatment.
BACKGROUND
Mitochondrial dysfunction is involved in neurodegenerative diseases, such as Huntington's disease (HD). 3-Nitropropionic acid (3-NP) is a mitochondrial toxin that specifically inhibits complex II of the electron transport chain (ETC) and is used to generate an experimental model of HD.


OBJECTIVE
To study the effect of fish liver oil (FO) over the mitochondrial dysfunction induced via partial ETC inhibition by 3-NP.


METHODS
This study was performed in rats and consisted of two phases: (i) administration of increasing doses of 3-NP and (ii) administration of FO for 14 days before to 3-NP. The rats' exploratory activity; complex I, II, III, and IV activities; and rearing behavior were observed. Additionally, the number of TUNEL-positive cells and various mitochondrial parameters, including oxygen consumption, transmembrane potential, adenosine triphosphate synthesis, and ETC activity, were measured.


RESULTS
We observed that FO exerted a protective effect against the 3-NP-induced toxicity, although complex II inhibition still occurred. Instead, this effect was related to strengthened mitochondrial complex III and IV activities.


CONCLUSIONS
Our results show that FO exerts a beneficial prophylactic effect against mitochondrial damage. Elucidating the mechanisms linking the effects of FO with its prevention of neurodegeneration could be the key to developing recommendations for FO consumption in neurological pathologies.
a Laboratorio de Neurobiología Molecular y Celular , Instituto Nacional de Neurología y Neurocirugía , Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg. Tlalpan, CP 14269 , Ciudad de México , México.
Marisol
http://orcid.org/0000-0001-7388-3738
M
Orozco-Ibarra
a Laboratorio de Neurobiología Molecular y Celular , Instituto Nacional de Neurología y Neurocirugía , Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg. Tlalpan, CP 14269 , Ciudad de México , México.
Jazmín
J
García-Morales
a Laboratorio de Neurobiología Molecular y Celular , Instituto Nacional de Neurología y Neurocirugía , Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg. Tlalpan, CP 14269 , Ciudad de México , México.
Francisco José
FJ
Calvo-Silva
b Laboratorio de Patología Experimental , Instituto Nacional de Neurología y Neurocirugía , Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg. Tlalpan, CP 14269 , Ciudad de México , México.
Francisca
F
Fernández-Valverde
a Laboratorio de Neurobiología Molecular y Celular , Instituto Nacional de Neurología y Neurocirugía , Av. Insurgentes Sur No. 3877 Col. La Fama, Deleg. Tlalpan, CP 14269 , Ciudad de México , México.
Norma
N
Serrano-García
D000818:Animals; D000975:Antioxidants; D003342:Corpus Striatum / Q000187:drug effects*; D003578:Cytochrome-c Peroxidase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology*; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D005395:Fish Oils; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D009243:NAD; D003578:Cytochrome-c Peroxidase; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; C015392:3-nitropropionic acid
Brain; Electron transport chain; Fish oil; Gadus morrhua; Huntington's disease; Mitochondria isolation; Mitochondrial function; Striatum