Effects of genistein on cognitive dysfunction and hippocampal synaptic plasticity impairment in an ovariectomized rat kainic acid model of seizure

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Abstract

The major objective of this study was to investigate the probable effects of genistein (one of the most important soy phytoestrogens-SPEs) on seizure-induced cognitive dysfunction, hippocampal early long-term potentiation (E-LTP) impairment and morphological damage to CA1 neurons in ovariectomized (OVX) rats.

Three weeks after ovariectomy, cannulae were implanted over the left lateral ventricle. After a 7-day recovery period, animals were injected by genistein (0.5 or 5 mg/kg) or vehicle during four consecutive days, each 24 h. One h after the last treatment, kainic acid (KA) or vehicle was perfused into the left lateral ventricle to induce generalized tonic-clonic seizures. Finally, 7 days later, spatial learning and memory of animals were examined using the Morris water maze (MWM) task, hippocampal E-LTP was assessed using in-vivo field potential recordings and the morphology of hippocampal CA1 area was examined using Fluoro-Jade C staining.

KA-induced generalized seizures resulted in spatial learning and memory impairment, E-LTP deficit and CA1 cell injury. Seizure-induced abnormalities improved partially only by the lower dose of genistein (0.5 mg/kg). However, genistein at the higher dose (5 mg/kg) did not have any beneficial effects. Also, genistein did not affect seizure activity.

It is concluded that genistein may have partially preventive effects against seizure-induced cognitive impairment in OVX rats. Also, it seems that such effects of genistein are correlated with its beneficial effects on hippocampal synaptic plasticity and morphology.

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