الفهرس 
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Abstract
Introduction:
Epilepsy is one of most common neurological problems in the world. Epilepsy is identified by recurrent and unprovoked seizures and sometimes is accompanied with some neurobiological, psychological and social consequences. On the contrary, the signs and symptoms of seizures transiently occur and represent abnormal excessive or synchronous neural activity in the brain. It is belived that epilepsy in women is more complicated in comparison with that in men, so there are some interference between seizure disorder and female hormones. In particular, in many epileptic women, ovarian cycle influences the seizures. For example, during menstrual cycle (catamenial epilepsy) and in the beginning of the puberty when ovarian cycle is first established, or at menopause when the menstrual cycle ceases, the occurrence or severity of seizures is changed.
There is an evidence showing the role of both male and female gonadal hormones on susceptibility in epilepsy. In men, sex hormones (testosterone and its breakdown products) also influence brain functions and may have an impact on seizures. The results of several studies showed that progesterone exerts anticonvulsive effects in both acute and chronic epilepsy models.
Estrogens affect neurotransmitter release, neurotransmitter receptors and neuronal excitability and thus may play an important role in seizure disorders. The results of some clinical and animal studies suggest that estrogens may have proconvulsant effects. It has been recently shown that estrogens may also produce anticonvulsant effects .These opposite effects of estrogens may be due to the duration of treatment, the latency prior to seizure testing, mode of administration, the applied dose of estrogen and
hormonal status, the region of nervous system or neurotransmitter system involved, the different seizure-inducing model used, and the sex.
Estrogen therapy is used for attenuation of postmenopausal problems. Despite the beneficial effects, estrogen therapy increases the risk of uterine cancer and neoplasms of the breast, especially after a long- term use. On this base, an alternative therapy could be the phytoestrogens from some vegetables such as soy which contains high concentration of phytoestrogens genistein, daidzein, glycitein, and their conjugates
Phytoestrogens structurally resemble endogenous estrogen that can directly bind to estrogen receptors (ERs), and therefore mimic estrogen functions such as gene expression. Both estrogen agonistic and antagonistic effects of soy isoflavones have been reported. It has also been shown that the soy isoflavones have inhibitory effects on tyrosine kinase, topoisomerase and angiogensis.
The beneficial effects of soy phytoestrogens on the nervous system including memory, cognitive functions and neuronal apoptosis have been reported. It has been shown that soy isoflavones have modulatory effects on neurotransmitters such as acetylcholine, dopamine, gamma-amino butyric acid (GABA) and glycine
Aim of the work:
Investigation of the effects of genistein on pentylenetetrazole-induced behavioral and neurochemical deficits in ovariectomized rats
Experimental Design:
Animals were divided into 9 groups:
Group1: [Sham-operated group]
group 2: [Control group]: Ovarectomized rats received PTZ vehicle (saline) .i.p. and genestein vehicle (absolute ethanol and Olive Oil 2: 3) p.o.
group 3: [PTZ-induced seizure group]: Ovarectomized rats receiving PTZ 90 mg/kg i.p.
Groups 4 to 7: [Genistein + PTZ groups]: Ovarectomized rats received
p.o. injections of 5, 10, 20 and 40 mg/kg genistein, respectively, thirty minutes before the injection of PTZ 90 mg/kg. i.p.
Groups 8 & 9: [Genistein-alone group]:Ovarectomized rats received p.o. injections of 10 and 20 mg/kg genistien, respectively followed by i.p. administration of saline
Measured Parameters:
- Mortality rate
- Time Duration and onset of seizure
- Histological examination of rat brain sections stained by Hematoxylin and Eosin (H&E).
- Neurochemical assessments of cortical levels/activities of:
• Nitric oxide.
• Reduced Glutathione (GSH).
• Lipid peroxidation.
- Estimation of apoptosis Marker using ELISSA Technique:
• Caspase-3.
- Immunohistochemical analyses of cortical Receptor Expression:
• Alpha Estrogen receptor experession (α ER).
• Beta Estrogen receptor experession (β ER)
• Glial fibrillary acid protein (GFAP)
Results:
Systemic acute administration of PTZ induced seizures, increased oxidative stress, and caused apoptosis and histological abnormalities. Pretreatment with genistein delayed seizure onset, reduced the seizure duration, improved oxidative stress profile, decreased estrogen receptor expression, reduced apoptosis, and improved the histopathological pattern. Overall, the genistein doses (10 and 20 mg/kg) showed the strongest protective effects.
Conclusion:
Overall, 20 mg/kg of genistein was demonstrated to be neuroprotective against PTZ-induced deficits in ovariectomized rats. The drug reduced seizure duration and attenuated PTZ induced histological abnormalities. The latter activity could be explained, at least partly, by its antioxidant, anti-apoptotic, and ER modulatory properties. Therefore, further studies are needed to investigate more effects of genistein on seizures and other neurodegenerative disorders.