In order to reassess the role of nerve growth factor (NGF) on rat basal forebrain cholinergic neurons (BFCNs) survival and/or phenotype maturation during the early postnatal life, we immunoneutralized NGF in vivo. Hybridoma cells producing the neutralizing anti-NGF monoclonal antibody alphaD11 were implanted in the lateral ventricle of the rat at different postnatal ages (P2, P8 and P15) and the effects on the number and the soma size of cholinacetyltransferase (ChAT) positive neurons were analysed 1, 2 or 3 weeks after the injection. A marked decrease in the number and in the soma size of BFCNs was observed implanting hybridoma cells at P2 and performing the analysis 1 week later. These effects are reversed 3 weeks after the implant of hybridoma cells at P2. At this time point, the levels of alphaD11 antibodies in the brain parenchyma are still in a vast molar excess over endogenous NGF. No effects on BFCNs were observed implanting alphaD11 cells at P15 while LGN neurons showed marked shrinkage. Our results demonstrate that the reduction in the number of ChAT-positive neurons during the first two postnatal weeks of anti-NGF treatment is not due to cell death. We conclude that NGF is not a survival factor for BFCNs, and that the influence of NGF on BFCNs cell maturation during the first 2 postnatal weeks is transient and reversible. Our results on tyrosine kinase (Trk) coexpression, suggest that NGF may cooperate with other factors in the cholinergic phenotype differentiation and maintenance after the second postnatal week.

Molnar, M., Tongiorgi, E., Avignone, E., Gonfloni, S., Ruberti, F., Domenici, L., et al. (1998). The effects of anti-nerve growth factor monoclonal antibodies on developing basal forebrain neurons are transient and reversible. EUROPEAN JOURNAL OF NEUROSCIENCE, 10(10), 3127-3140.

The effects of anti-nerve growth factor monoclonal antibodies on developing basal forebrain neurons are transient and reversible

GONFLONI, STEFANIA;
1998-10-01

Abstract

In order to reassess the role of nerve growth factor (NGF) on rat basal forebrain cholinergic neurons (BFCNs) survival and/or phenotype maturation during the early postnatal life, we immunoneutralized NGF in vivo. Hybridoma cells producing the neutralizing anti-NGF monoclonal antibody alphaD11 were implanted in the lateral ventricle of the rat at different postnatal ages (P2, P8 and P15) and the effects on the number and the soma size of cholinacetyltransferase (ChAT) positive neurons were analysed 1, 2 or 3 weeks after the injection. A marked decrease in the number and in the soma size of BFCNs was observed implanting hybridoma cells at P2 and performing the analysis 1 week later. These effects are reversed 3 weeks after the implant of hybridoma cells at P2. At this time point, the levels of alphaD11 antibodies in the brain parenchyma are still in a vast molar excess over endogenous NGF. No effects on BFCNs were observed implanting alphaD11 cells at P15 while LGN neurons showed marked shrinkage. Our results demonstrate that the reduction in the number of ChAT-positive neurons during the first two postnatal weeks of anti-NGF treatment is not due to cell death. We conclude that NGF is not a survival factor for BFCNs, and that the influence of NGF on BFCNs cell maturation during the first 2 postnatal weeks is transient and reversible. Our results on tyrosine kinase (Trk) coexpression, suggest that NGF may cooperate with other factors in the cholinergic phenotype differentiation and maintenance after the second postnatal week.
ott-1998
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
Cell Transplantation; Time Factors; Biological Assay; Rats, Wistar; Immunohistochemistry; PC12 Cells; Hybridomas; Nerve Growth Factors; Prosencephalon; Cerebral Cortex; COS Cells; Age Factors; Cholinergic Fibers; Cell Count; Receptor, trkA; Cell Differentiation; Cholinesterases; Antibody Specificity; Hippocampus; Injections, Intraventricular; Chick Embryo; Receptor Protein-Tyrosine Kinases; Rats; Animals; Receptors, Nerve Growth Factor; Choline O-Acetyltransferase; Neurons; Proto-Oncogene Proteins; Antibodies, Monoclonal; Receptor, Ciliary Neurotrophic Factor; Cell Size
Molnar, M., Tongiorgi, E., Avignone, E., Gonfloni, S., Ruberti, F., Domenici, L., et al. (1998). The effects of anti-nerve growth factor monoclonal antibodies on developing basal forebrain neurons are transient and reversible. EUROPEAN JOURNAL OF NEUROSCIENCE, 10(10), 3127-3140.
Molnar, M; Tongiorgi, E; Avignone, E; Gonfloni, S; Ruberti, F; Domenici, L; Cattaneo, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/9144
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