الفهرس 
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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.