A glia-derived signal regulating neuronal differentiation.
Astrocytes are present in large numbers in the nervous system, are associated with synapses, and propagate ionic signals. Astrocytes influence neuronal physiology by responding to and releasing neurotransmitters, but the mechanisms that establish the close interaction between these cells are not defined. Here we use hippocampal neurons in culture to demonstrate that vasoactive intestinal polypeptide (VIP) promotes neuronal differentiation through activity-dependent neurotrophic factor (ADNF), a protein secreted by VIP-stimulated astroglia. ADNF is produced by glial cells and acts directly on neurons to promote glutamate responses and morphological development. ADNF causes secretion of neurotrophin 3 (NT-3), and both proteins regulate NMDA receptor subunit 2A (NR2A) and NR2B. These data suggest that the VIP-ADNF-NT-3 neuronal-glial pathway regulates glutamate responses from an early stage in the synaptic development of excitatory neurons and may also contribute to the known effects of VIP on learning and behavior in the adult nervous system.
Blondel
O
O
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Collin
C
C
McCarran
W J
WJ
Zhu
S
S
Zamostiano
R
R
Gozes
I
I
Brenneman
D E
DE
McKay
R D
RD
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
D008869:Microtubule-Associated Proteins; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D020933:Neurotrophin 3; D009842:Oligopeptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C410622:activity-dependent neurotrophic factor; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid