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The Neurotrophin-Inducible GeneVgfRegulates Hippocampal Function and Behavior through a Brain-Derived Neurotrophic Factor-Dependent Mechanism
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| Zeitschriftentitel: | The Journal of Neuroscience |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | The Journal of Neuroscience, 28, 2008, 39, S. 9857-9869 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>VGF is a neurotrophin-inducible, activity-regulated gene product that is expressed in CNS and PNS neurons, in which it is processed into peptides and secreted. VGF synthesis is stimulated by BDNF, a critical regulator of hippocampal development and function, and two VGF C-terminal peptides increase synaptic activity in cultured hippocampal neurons. To assess VGF function in the hippocampus, we tested heterozygous and homozygous VGF knock-out mice in two different learning tasks, assessed long-term potentiation (LTP) and depression (LTD) in hippocampal slices from VGF mutant mice, and investigated how VGF C-terminal peptides modulate synaptic plasticity. Treatment of rat hippocampal slices with the VGF-derived peptide TLQP62 resulted in transient potentiation through a mechanism that was selectively blocked by the BDNF scavenger TrkB–Fc, the Trk tyrosine kinase inhibitor K252a (100 n<jats:sc>m</jats:sc>), and tPA STOP, an inhibitor of tissue plasminogen activator (tPA), an enzyme involved in pro-BDNF cleavage to BDNF, but was not blocked by the NMDA receptor antagonist APV, anti-p75<jats:sup>NTR</jats:sup>function-blocking antiserum, or previous tetanic stimulation. Although LTP was normal in slices from VGF knock-out mice, LTD could not be induced, and VGF mutant mice were impaired in hippocampal-dependent spatial learning and contextual fear conditioning tasks. Our studies indicate that the VGF C-terminal peptide TLQP62 modulates hippocampal synaptic transmission through a BDNF-dependent mechanism and that VGF deficiency in mice impacts synaptic plasticity and memory in addition to depressive behavior.</jats:p> |
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| Umfang: | 9857-9869 |
| ISSN: |
0270-6474
1529-2401 |
| DOI: | 10.1523/jneurosci.3145-08.2008 |