GONADAL HORMONES REGULATE KCC2 EXPRESSION IN RAT SUBSTANTIA NIGRA RETICULATA
Abstract number :
2.047
Submission category :
Year :
2002
Submission ID :
839
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Aristea S. Galanopoulou, Solomon L. Moshe. Neurology, Albert Einstein College of Medicine, Bronx, NY; Neuroscience, Albert Einstein College of Medicine, Bronx, NY; Pediatrics, Albert Einstein College of Medicine, Bronx, NY
RATIONALE: The GABA(A) responsive neurons of the rat substantia nigra pars reticulata (SNR) have sex and age specific effects on seizures, which are organized by the early postnatal presence of testosterone. The neuronal specific potassium-chloride cotransporter KCC2 mediates the functional switch of GABA(A) receptors from depolarizing to hyperpolarizing. We have recently provided evidence that high levels of KCC2 mRNA expression in SNR neurons may be required for the development of SNR-mediated seizure suppression in response to GABA(A) agonists. In this study, we have investigated whether (i) gonadal hormones also regulate KCC2 expression in rat SNR, and (ii) whether their effects may explain the sexually dimorphic and age-specific patterns of KCC2 expression and GABA(A) receptor function in seizure control.
METHODS: KCC2 specific in situ hybridization on sagittal SNR sections from PN15 male and female rats was used to determine the effects of 17[beta]-estradiol (5[mu]g SC per rat), testosterone propionate (100[mu]g SC per rat), or dihydrotestosterone (180 [mu]g SC per rat) or oil on the expression of KCC2 mRNA in rat SNR. Comparisons of the cellular signal densities of KCC2-positive SNR neurons were performed among the different experimental groups.
RESULTS: Both acute (4 hours) and long-term (52 hours) exposure to 17[beta]-estradiol decreased KCC2 mRNA in male SNR neurons. 17[beta]-estradiol did not change KCC2 mRNA expression in females. Both acute and long-term exposure to either testosterone or dihydrotestosterone augmented the neuronal expression of KCC2 mRNA in both male and female SNR.
CONCLUSIONS: (1) Estradiol downregulates KCC2 mRNA expression in infantile male SNR, and may thus promote the appearance of the muscimol-sensitive proconvulsant region of the male PN15 SNR. (2) Estradiol has no effect on the expression of KCC2 mRNA in the female SNR, and this may explain the lack of muscimol-sensitive proconvulsant SNR region in females. (3) Androgens elevate KCC2 mRNA expression in rat SNR of both sexes, and may be involved in the prepubertal upregulation of KCC2 and thus the development of GABA(A) sensitive SNR-mediated seizure suppressing systems.
[Supported by: EFA grant and RO1 NS20253]