title: Nerve growth factor and brain-derived neurotrophic factor increase neurotransmitter release in the rat visual cortex.
abstract: A number of experiments have shown that neurotrophins are involved in the development and plasticity of the visual cortex (Bonhoeffer, T., Curr. Op. Neurobiol., 6, 119, 1996). A possible mechanism underlying these effects is the neurotrophin modulation of synaptic transmission. We investigated whether nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) can modulate the release of neurotransmitter in the rat visual cortex at the peak of the critical period for plasticity (P23). The release of glutamate, acetylcholine and gamma-aminobutyric acid (GABA) from visual cortical synaptosomes was analysed in continuous perfusion conditions. We found that NGF enhances the depolarization-evoked release of glutamate (approximately 90%) and acetylcholine (approximately 35%) but not that of GABA. By contrast, BDNF enhances the depolarization-evoked release of all three neurotransmitters investigated (approximately 30%). BDNF and NGF were ineffective on basal release of neurotransmitters. The effect of NGF was not blocked by cholinergic antagonists atropine and mecamylamine. NGF and BDNF potentiation of transmitter release was strongly but not completely blocked by K252a, a tyrosine kinase inhibitor. The role of TrkA and p75NTR receptors was investigated in NGF-induced potentiation of glutamate release. Block of NGF binding to p75NTR using specific blocking antibodies (REX-IgG) slightly but significantly reduced the effect of NGF. Activation of TrkA in isolation by RTA-IgG, an antibody that specifically activates TrkA, was less effective than activation of both receptors by NGF. These results show that neurotrophin action on neurotransmitter release was mostly mediated by Trk receptors with p75NTR having a little but significant positive role. Antigen blot analysis showed the presence of TrkA, TrkB and p75NTR receptors in the visual cortex.
authors.affiliation: Istituto di Farmacologia, Universita' di Genova, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sala
authors.forename: A
authors.initials: A
authors.lastname: Viegi
authors.forename: F M
authors.initials: FM
authors.lastname: Rossi
authors.forename: T
authors.initials: T
authors.lastname: Pizzorusso
authors.forename: G
authors.initials: G
authors.lastname: Bonanno
authors.forename: M
authors.initials: M
authors.lastname: Raiteri
authors.forename: L
authors.initials: L
authors.lastname: Maffei
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004357:Drug Synergism; D018698:Glutamic Acid / Q000378:metabolism; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D014793:Visual Cortex / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D018698:Glutamic Acid; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D002118:Calcium