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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-2-25
pubmed:abstractText
The inhibitory neurotransmitter GABA may act as a trophic signal for developing monoamine neurons in embryonic rat brain, because GABA neurons and their receptors appear in brainstem during generation of monoamine neurons. To test this hypothesis, we used dissociated cell cultures from embryonic day 14 rat brainstem, which contains developing serotonin (5-HT), noradrenaline (tyrosine hydroxylase; TH), and GABA neurons. Immunocytochemistry and reverse transcription-PCR (RT-PCR) revealed the presence of multiple alpha, beta, gamma, and delta subunits in these cultures. Competitive RT-PCR demonstrated high levels of beta3 subunit transcripts. Expression of functional GABAA receptors was demonstrated using 36Cl- flux assays. To investigate GABAergic regulation of neuronal survival and growth, cultures were treated for 1-3 d in vitro with 10 microM GABA and/or GABAA antagonist (bicuculline or the pesticide dieldrin). The effects of treatments were quantified by analysis of immunoreactive 5-HT, TH, and GABA neurons. GABAA receptor ligands differentially regulated neuronal survival and growth depending on neurotransmitter phenotype. GABA exerted positive effects on monoamine neurons, which were countered by bicuculline (and dieldrin, 5-HT neurons only). By itself, bicuculline produced inhibitory effects on both 5-HT and TH neurons, whereas dieldrin potently inhibited 5-HT neurons only. GABA neurons responded positively to both antagonists, but more strongly to bicuculline. Taken together, these results demonstrate that the activation/inhibition of GABAA receptors produces opposite effects on the development of embryonic monoamine and GABA neurons. This suggests that these neurotransmitter phenotypes may express GABAA receptors that differ in fundamental ways, and these differences determine the developmental responses of these cells to GABAergic stimuli.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2420-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9065503-Animals, pubmed-meshheading:9065503-Bicuculline, pubmed-meshheading:9065503-Brain Stem, pubmed-meshheading:9065503-Cell Division, pubmed-meshheading:9065503-Cell Survival, pubmed-meshheading:9065503-Cells, Cultured, pubmed-meshheading:9065503-Chlorides, pubmed-meshheading:9065503-Dieldrin, pubmed-meshheading:9065503-Embryo, Mammalian, pubmed-meshheading:9065503-Macromolecular Substances, pubmed-meshheading:9065503-Neurons, pubmed-meshheading:9065503-Norepinephrine, pubmed-meshheading:9065503-Rats, pubmed-meshheading:9065503-Receptors, GABA-A, pubmed-meshheading:9065503-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:9065503-Serotonin, pubmed-meshheading:9065503-Transcription, Genetic, pubmed-meshheading:9065503-Tyrosine 3-Monooxygenase, pubmed-meshheading:9065503-gamma-Aminobutyric Acid
pubmed:year
1997
pubmed:articleTitle
GABAA receptors mediate trophic effects of GABA on embryonic brainstem monoamine neurons in vitro.
pubmed:affiliation
Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.