Abstract

Huntington disease (HD), a neurodegenerative disorder, is characterized by selective atrophy and cell loss within the striatum. 3-nitropropionic acid (3-NP) is a mitochondrial toxin that induces experimental HD-like disorders. Currently, although there is no treatment that can prevent the striatal neuropathology, cysteamine is considered one of the most promising candidate drugs for HD. Previous studies showed that cysteamine modulates 3-NP-induced HD, via several mechanisms; however, its effect on amino-acids profile and mitochondrial function was not tested before, which is the main aim of the current study. Male Wistar albino rats (200-250 g) were injected subcutaneously by 3-NP (20 mg/ kg/ day for 7 days), to serve as positive control group. Another group received cysteamine intraperitonealy in a building dose from 25 up to 75 mg/kg/day for 7 days, one hour before 3-NP. Normal untreated rats were used as negative control. The striatal biochemical parameters and serum amino acid pattern were assessed one hour after the last 3-NP injection.  The mitochondrial toxin resulted in significant decrease in striatal citrate synthase (CS), creatine kinase (CK) and glutathione (GSH) accompanied by a marked increase in nitric oxide (NO) activity/ content. Significant reduction in branched chain amino acids, glycine, alanine, serine, taurine, tyrosine and histidine was also demonstrated in 3-NP- treated rats. Cysteamine administration markedly improved the mitochondrial function as exhibited by restoration of CS activity; however, no effect was noticed on the rest of the striatal biochemical parameters. In addition, some of the amino acids altered by 3-NP were ameliorated by cysteamine. In conclusion, results of the present study explored the importance of amino acid pattern in the pathogenesis of HD and confirmed the neuroprotective efficacy of cysteamine against HD which may be related at least partly, to its influence on amino acid metabolism and enhancement of mitochondrial function.

Key words: Huntington disease, cysteamine, oxidative stress, mitochondria, amino acids.

Abbreviation

Abbreviations: HD, Huntington disease; 3-NP, 3-nitropropionic acid; CAG, cytosine- adenine- guanine trinucleotide; CS, citrate synthase; CK, creatine kinase; GSH, glutathione; NO, nitric oxide; SDH, succinate dehydrogenase; tTGase, tissue transglutaminase; BCAA, branched chain amino acids and BDNF, brain-derived neurotrophic factor.