NGF-mediated synaptic sprouting in the cerebral cortex of lesioned primate brain.
In the present study, coronal brain sections of cortically devascularized non-human primates (Cercopithecus aethiops) were used to assess the lesion-associated synaptic loss, and the effect of exogenous nerve growth factor (NGF) in preventing or reversing this neurodegeneration. The sections were immunolabeled with antibodies against the synaptic marker protein synaptophysin (SYN), as well as choline acetyltransferase (ChAT) and parvalbumin (PV) markers that identify cholinergic neurons and interneurons, respectively. We found that, compared to sham-operated animals, in the lesioned vehicle treated animals SYN immunoreactivity near the lesioned site in the frontoparietal cortex was decreased by 31%. Similarly, corrected optical density values of immunostained sections specific for ChAT in the nucleus basalis of Meynert (ipsilateral to the lesion) decreased by 20% and PV-immunoreactive neurons near the lesion decreased by 47%. In contrast, NGF-treated lesioned animals showed levels of SYN, ChAT, and PV immunoreactivity similar to sham controls. These results are consistent with previous studies and support the view that NGF may not only prevent neurodegenerative changes after neocortical infarction by protecting vulnerable neurons, but also is capable of inducing sprouting and synaptogenesis.
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla 92093-0624, USA.
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Burgos
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Cuello
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Liberini
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Pioro
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Masliah
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D010320:Parvalbumins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013377:Substantia Innominata / Q000166:cytology / Q000201:enzymology; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism
D009414:Nerve Growth Factors; D010320:Parvalbumins; D016708:Synaptophysin; D002795:Choline O-Acetyltransferase