Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington's disease phenotype.
An experimental animal model of Huntington's disease (HD) phenotype was induced using the mycotoxin 3-nitropropionic acid (3-NP) and was well characterized behaviorally, neurochemically, morphometrically and histologically. Administration of 3-NP caused a reduction in prepulse inhibition (PPI) of acoustic startle response, locomotor hyper- and/or hypoactivity, bilateral striatal lesions, brain oxidative stress, and decreased striatal gamma-aminobutyric acid (GABA) levels. Taurine is a semi-essential beta-amino acid that was demonstrated to have both antioxidant and GABA-A agonistic activity. In this study, treatment with taurine (200 mg/kg daily for 3 days) prior to 3-NP administration reversed both reduced PPI response and locomotor hypoactivity caused by 3-NP injection. Taurine pretreatment also caused about 2-fold increase in GABA concentration compared to 3-NP-treated animals. In addition, taurine demonstrated antioxidant activity against oxidative stress induced by 3-NP administration as evidenced by the reduced striatal malondialdehyde (MDA) and elevated striatal glutathione (GSH) levels. Histochemical examination of striatal tissue showed that prior administration of taurine ahead of 3-NP challenge significantly increased succinate dehydrogenase (SDH) activity compared to 3-NP-treated animals. Histopathological examination further affirmed the neuroprotective effect of taurine in 3-NP-induced HD in rats. Taken together, one may conclude that taurine has neuroprotective role in the current HD paradigm due, at least partly, to its indirect antioxidant effect and GABA agonistic action.
Tadros
Mariane G
MG
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Khalifa
Amani E
AE
Abdel-Naim
Ashraf B
AB
Arafa
Hossam M M
HM
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced*; D008297:Male; D009043:Motor Activity; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress; D010641:Phenotype; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects; D013654:Taurine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D013654:Taurine; D005680:gamma-Aminobutyric Acid; C015392:3-nitropropionic acid