Sex- and cell-type-specific patterns of GABAA receptor and estradiol-mediated signaling in the immature rat substantia nigra

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Abstract

The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABA A receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7β-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 17β-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, 17β-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17β-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.

Original languageEnglish (US)
Pages (from-to)2423-2430
Number of pages8
JournalEuropean Journal of Neuroscience
Volume23
Issue number9
DOIs
StatePublished - May 2006

Fingerprint

Substantia Nigra
GABA-A Receptors
Estradiol
Muscimol
Neurons
Parvalbumins
Seizures
GABA-A Receptor Agonists
Calcium
Gramicidin
Sex Differentiation
Antibodies
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Baths
Membrane Potentials
Genes
Pars Reticulata
Carrier Proteins
Transcription Factors

Keywords

  • Dopaminergic
  • Immunochemistry
  • Parvalbumin
  • Patch clamp

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Sex- and cell-type-specific patterns of GABAA receptor and estradiol-mediated signaling in the immature rat substantia nigra",
abstract = "The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABA A receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7β-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 17β-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, 17β-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17β-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.",
keywords = "Dopaminergic, Immunochemistry, Parvalbumin, Patch clamp",
author = "Galanopoulou, {Aristea S.}",
year = "2006",
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}

TY - JOUR

T1 - Sex- and cell-type-specific patterns of GABAA receptor and estradiol-mediated signaling in the immature rat substantia nigra

AU - Galanopoulou, Aristea S.

PY - 2006/5

Y1 - 2006/5

N2 - The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABA A receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7β-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 17β-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, 17β-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17β-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.

AB - The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABA A receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7β-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 17β-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, 17β-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17β-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.

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SP - 2423

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JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

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