Nerve growth factor induced modification of presynaptic elements in adult visual cortex in vivo.
Nerve growth factor (NGF) has been shown to play important roles in neuronal survival, growth and differentiation. Recently, we have found that intracortical infusion of NGF into adult cat visual cortex can recreate ocular dominance plasticity, suggesting that NGF is also involved in activity-dependent modification of synaptic connectivity in the adult brain. To further explore the mechanisms of NGF-induced plasticity in adult visual cortex, we studied two presynaptic markers: GAP-43 and synaptophysin. Immunocytochemical staining showed that NGF-treatment of adult visual cortex selectively increased the level of the phosphorylated form of GAP-43, while the total level of GAP-43 was not changed. These results demonstrate that NGF-treatment stimulates phosphorylation processes of GAP-43 in vivo. In addition, NGF-treatment of adult visual cortex increased the level of synaptophysin immunoreactivity. Since the phosphorylated form of GAP-43 is known to be enriched in the membrane skeleton of growth cones and of developing synapses, and the phosphorylation of GAP-43 has been linked with events that underlie synaptic plasticity, and since synaptophysin is a major component of presynaptic vesicles, our results suggest that NGF-treatment of adult visual cortex modulates presynaptic terminals, possibly by inducing axonal sprouting and formation of new synapses, and that these changes may play a role in the NGF-induced functional plasticity.
Department of Ophthalmology, University of British Columbia, Vancouver, Canada.
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Liu
K F
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Meiri
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Cynader
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Gu
D000818:Animals; D015415:Biomarkers; D002415:Cats; D019922:GAP-43 Protein; D006801:Humans; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000032:analysis / Q000378:metabolism*; D014793:Visual Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D015415:Biomarkers; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D011994:Recombinant Proteins; D016708:Synaptophysin