VIP and PACAP potentiate the action of glutamate on BDNF expression in mouse cortical neurones.
In view of the neurotrophic effect of vasoactive intestinal peptide (VIP), the regulation of brain-derived neurotrophic factor (BDNF) expression by VIP and the related peptide pituitary adenylate cyclase-activating polypeptide (PACAP) was analysed by Northern blot in primary cultures of cortical neurones. Results reported in this article demonstrate that VIP and PACAP stimulate the expression of BDNF mRNA in primary cultures of cortical neurones and astrocytes. In primary cultures of cortical neurones, induction of BDNF mRNA by VIP and PACAP is completely inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and AP5, therefore indicating that VIP and PACAP do not stimulate BDNF expression directly but rather by potentiating the effect of glutamate tonically released by neurones and acting at NMDA receptors. In addition to its neurotrophic effects, BDNF has been shown to be involved in neuronal plasticity and results reported here suggest that by stimulating BDNF expression, VIP and PACAP could modulate synaptic plasticity in the cerebral cortex.
Pellegri
G
G
Laboratoire de Recherche Neurologiche, Institut de Physiologie et Service de Neurologie du CHUV, Faculté de Médecine, Université de Lausanne, Switzerland.
Magistretti
P J
PJ
Martin
J L
JL
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C000211:2-amino-3-phosphonopropionic acid; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D000409:Alanine