GABA-glutamate interaction in the control of BDNF expression in hypothalamic neurons.
Brain derived-neurotrophic factor (BDNF) belongs to the neurotrophin family and regulates the survival, differentiation and maintenance of function in different neuronal populations. We previously reported that glutamate increases the expression of BDNF mRNA, its four transcripts and the BDNF peptide in fetal hypothalamic neurons, essentially through NMDA receptor activation. In the present study, we investigated whether GABA interacts with glutamate in the regulation of BDNF gene expression. BDNF and Trk B (BDNF receptor) mRNAs were determined by RNAse protection assay. BDNF transcripts expression levels were evaluated by semi-quantitative RT-PCR. BDNF peptide content was analyzed by enzyme immunoassay (ELISA).We found that picrotoxin (a GABA(A) receptor antagonist) stimulated BDNF mRNA expression and that GABA decreased the glutamate-induced augmentation with no effect on the expression of mRNA encoding the BDNF receptor, Trk B. Measurements of BDNF transcripts levels showed that transcripts containing exons I and III were increased by picrotoxin, whereas those containing exons II and IV were unchanged. GABA solely diminished the glutamate-stimulated expression of transcripts containing exon III. In addition, GABA also inhibited the stimulatory effect of glutamate on BDNF peptide content. Our findings show an interaction between glutamate and GABA on BDNF expression (mRNA, transcripts and peptide) in fetal hypothalamic neurons.
Marmigère
Frédéric
F
Laboratoire de Plasticité Cérébrale, UMR 5102 CNRS, Université Montpellier 2, CC 090, Place Eugène Bataillon, France.
Rage
Florence
F
Tapia-Arancibia
Lucia
L
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D023282:Nuclease Protection Assays; D010852:Picrotoxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D018756:GABA Antagonists; D018698:Glutamic Acid; D010852:Picrotoxin; D012333:RNA, Messenger; D020813:Receptor, trkB; D005680:gamma-Aminobutyric Acid