الفهرس | Only 14 pages are availabe for public view |
Abstract Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric abnormalities. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD. Phytoestrogens have well-established neuroprotective and memory enhancing effects with better side effect profile in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effects of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol. Results showed that systemic administration of 3-NPA for 4 days decreased animals body temperature and weight, significantly decreased % PPI, impaired locomotor activity and decreased retention latencies in the passive avoidance task. It also increased striatal, cortical and hippocampal oxidative stress through increasing lipid peroxidation and decreasing catalase activity and reduced glutathione levels. Moreover, 3-NPA significantly increased acetylcholinesterase activity (AChE), cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions also decreased ATP levels and increased prostaglandin E2 (PGE2) production and Bax/Bcl-2 ratio. Pretreatment with genistein and 17β-estradiol maintained animals’ temperature and weight, restored % PPI, attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task. They also improved the oxidative stress profile, increased ATP levels and attenuated 3-NPA-induced increase in AChE activity and COX-2 and iNOS expressions. Genistein also decreased PGE2 production and Bax/Bcl-2 ratio in the striatum. Overall, the highest genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests a neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed-at least partly- to its antioxidant, anti-inflammatory, antiapoptotic and cholinesterase inhibitory activities. |