Sex- and Cell-type-specific Patterns of Gabaa Receptor and Estradiol-mediated Signaling in the Immature Rat Substantia Nigra.
From: Department of Neurology and Einstein/Montefiore Comprehensive Epilepsy Center, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Kennedy Center Rm 311, Bronx, NY 10461, USA. agalan@aecom.yu.edu
The European journal of neuroscience
- Publish Date: May 2006
- ISSN: 0953-816X
- Volume: 23
- Issue: 9
- Pages: 2423-30
- Medium: Print
- Language: English
- Citation (JAMA): Galanopoulou Aristea S, et al. Sex- and Cell-type-specific Patterns of Gabaa Receptor and Estradiol-mediated Signaling in the Immature Rat Substantia Nigra.. Eur. J. Neurosci. May 2006;23:2423-30
Abstract
The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABAA receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7beta-estradiol down-regulates KCC2 expression only in the presence of depolarizing GABAA receptor responses. The hypothesis tested here was that GABAA receptors and estradiol also regulate the expression of the phosphorylated form of the transcription factor cAMP responsive element binding protein (phosphoCREB), in PN15 rat SNR and substantia nigra pars compacta (SNC). Rats were injected with muscimol or 17beta-estradiol or their vehicles, and killed 1 h later. Sections were stained with an antibody specific for phosphoCREB alone or counterstained with either tyrosine hydroxylase (TH)- or parvalbumin (PRV)-specific antibodies. Muscimol increased phosphoCREB-ir in male but not in female SN neurons. Using gramicidin perforated patch clamp of PN14-15 SNC neuron, it was shown that muscimol bath application depolarized male SNC neurons but did not significantly alter membrane potential in females. In males, 17beta-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17beta-estradiol did not influence phosphoCREB expression in PRV-ir SNR cells, but increased it in the dopaminergic SN neurons. These data suggest that GABAA receptor activation and estradiol promote the sexual differentiation of the SN in a cell-type-specific manner, by influencing calcium-regulated gene transcription, and therefore promoting the acquisition of sex-specific roles of the SN in movement and seizure control.
Mesh Headings (Keywords): Animals, Animals, Newborn, CREB-Binding Protein, Cell Count, Estradiol, Female, GABA Agonists, Immunohistochemistry, Male, Muscimol, Neurons, Patch-Clamp Techniques, Pregnancy, Rats, Rats, Sprague-Dawley, Receptors, GABA-A, Sex Characteristics, Substantia Nigra, Tyrosine 3-Monooxygenase
Check for Full Text / PubMed Unique Identifier (PMID): 16706849
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