phytoestrogens and Seizures

Estrogenic compounds have been documented in literature to exert neuroprotective effects. This study investigated the potential neuroprotective effect of genistein; a phytoestrogen at doses of 5, 10, 20, and 40 mg/kg p.o. in ovariectomized rats challenged with pentylenetetrazole (PTZ) 90 mg/kg i.p. 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. In conclusion, the current study suggests that genistein exhibits neuroprotective effects against PTZ-induced seizures. Such effects might be attributed to its estrogenic, antioxidant, and/or anti-apoptotic properties.

Topics: Animals; Brain; Brain Chemistry; Dose-Response Relationship, Drug; Female; Genistein; Neuroprotective Agents; Ovariectomy; Pentylenetetrazole; Phytoestrogens; Rats; Rats, Wistar; Seizures

Topics: Animals; Brain-Derived Neurotrophic Factor; CA1 Region, Hippocampal; Female; Genistein; Hippocampus; Ovariectomy; Phytoestrogens; Rats; Rats, Wistar; Seizures

Genistein, a major source of phytoestrogen exposure for humans and animals, has been shown to mediate neuroprotection in Alzheimer's disease and status epilepticus. In the present study, we investigated the effect of genistein on pentylenetetrazole-induced seizures in ovariectomized mice and the possible involvement of estrogenic and serotonergic pathways in the probable effects of genistein. Intraperitoneal (i.p.) administration of genistein (10 mg/kg) significantly increased the seizure threshold 30 min prior to induction of seizures 14 days after ovariectomy surgery. Administration of fulvestrant (1 mg/kg, i.p.), an estrogen receptor antagonist, completely reversed the anticonvulsant effect of genistein (10 mg/kg) in ovariectomized mice. Administration of the antagonist of serotonin receptor (5-HT3), tropisetron (10 mg/kg, i.p.), eliminated the anticonvulsant effect of genistein, whereas co-administration of m-chlorophenylbiguanide (5-HT3 receptor agonist; 1 mg/kg) and a non-effective dose of genistein (5 mg/kg) increased the seizure threshold. To conclude, it seems that estrogenic/serotonergic systems might be involved in the anticonvulsant properties of genistein.

Topics: Animals; Anticonvulsants; Biguanides; Dose-Response Relationship, Drug; Fabaceae; Female; Genistein; Mice; Pentylenetetrazole; Phytoestrogens; Plant Extracts; Receptors, Estrogen; Receptors, Serotonin; Seizures; Serotonin Receptor Agonists

Autism spectrum disorders (ASDs) are a group of devastating neurodevelopmental syndromes that affect up to 1 in 68 children. Despite advances in the identification of ASD risk genes, the mechanisms underlying ASDs remain unknown. Homozygous loss-of-function mutations in Contactin Associated Protein-like 2 (CNTNAP2) are strongly linked to ASDs. Here we investigate the function of Cntnap2 and undertake pharmacological screens to identify phenotypic suppressors. We find that zebrafish cntnap2 mutants display GABAergic deficits, particularly in the forebrain, and sensitivity to drug-induced seizures. High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems. Finally, we find that estrogen receptor agonists elicit a behavioral fingerprint anti-correlative to that of cntnap2 mutants and show that the phytoestrogen biochanin A specifically reverses the mutant behavioral phenotype. These results identify estrogenic compounds as phenotypic suppressors and illuminate novel pharmacological pathways with relevance to autism.

Topics: Animals; Animals, Genetically Modified; Autistic Disorder; Disease Models, Animal; Estrogens; Gene Expression Regulation; Genistein; Green Fluorescent Proteins; Humans; Larva; Luminescent Proteins; Membrane Proteins; Motor Activity; Mutation; Nerve Tissue Proteins; Phenotype; Phytoestrogens; Psychotropic Drugs; Seizures; Sleep-Wake Transition Disorders; Vesicular Glutamate Transport Protein 2; Zebrafish

To study the different effects of soy extract on pentylenetetrazole (PTZ)-induced seizures in the presence and absence of ovarian hormones in rats, and the gender-dependent differences in the effects of phytoestrogens on behavior.. Male and female Wistar rats were randomly divided into nine groups with eight in each, namely, male-saline (M-saline), male-low-dose soy (M-LDS), male-high-dose soy (M-HDS), sham-saline (Sh-saline), sham-low-dose soy (Sh-LDS), sham-high-dose soy (Sh-HDS), ovariectomized-saline (OVX-saline), ovariectomized-low-dose soy (OVX-LDS) and ovariectomized-high-dose soy (OVX-HDS). The rats of groups 7 to 9 were ovariectomized under ketamine anesthesia. The rats of groups 2, 5 and 8 were treated by 20 mg/kg of soy extract while the animals of groups 3, 6 and 9 received 60 mg/kg of soy extract for two weeks. In groups 1, 4 and 7, saline was injected instead of soy extract. The animals were then injected by a single dose of PTZ (90 mg/kg body weight, intraperitoneally) and placed in a plexiglas cage and the latency to minimal clonic seizure (MCS) and generalized tonic-clonic seizure (GTCS) was recorded.. Both MCS and GTCS latency in M-LDS and M-HDS groups was significantly lower than that in M-saline group (P<0.05 or P<0.01). Treatment for female sham rats by soy extract did not affect MCS and GTCS latency. The animals of OVX-LDS and OVX-HDS groups had lower MCS and GTCS latency in comparison with OVX-saline group (P<0.05 or P<0.01).. It is concluded that the phytoestrogens of soy affect seizure severity induced by PTZ, but their effects are different in the presence or absence of ovarian hormones. However, further studies are necessary to be done.

Topics: Animals; Anticonvulsants; Female; Glycine max; Male; Ovariectomy; Pentylenetetrazole; Phytoestrogens; Plant Extracts; Rats; Rats, Wistar; Seizures