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Titolo:
Intraparenchymal NGF infusions rescue degenerating cholinergic neurons
Autore:
Tuszynski, MH;
Indirizzi:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA Univ Calif SanDiego La Jolla CA USA 92093 urosci, La Jolla, CA 92093 USA Vet Affairs Med Ctr, San Diego, CA 92161 USA Vet Affairs Med Ctr San Diego CA USA 92161 d Ctr, San Diego, CA 92161 USA
Titolo Testata:
CELL TRANSPLANTATION
fascicolo: 5, volume: 9, anno: 2000,
pagine: 629 - 636
SICI:
0963-6897(200009/10)9:5<629:INIRDC>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; NUCLEUS BASALIS MAGNOCELLULARIS; PRIMATE BRAIN; NEUROTROPHIC FACTOR; SPATIAL MEMORY; AGED RATS; FOREBRAIN; PREVENTS; ATROPHY; SYSTEM;
Keywords:
nerve growth factor (NGF); cholinergic system; memory; neurotrophic factors; Alzheimer's disease; aging; drug delivery; regeneration;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Tuszynski, MH Univ Calif San Diego, Dept Neurosci 0626, La Jolla, CA 92093USA Univ Calif San Diego La Jolla CA USA 92093 la, CA 92093 USA
Citazione:
M.H. Tuszynski, "Intraparenchymal NGF infusions rescue degenerating cholinergic neurons", CELL TRANSP, 9(5), 2000, pp. 629-636

Abstract

Nerve growth factor (NGF) exerts both trophic (cell survival) and tropic (axonal growth-promoting) effects on several neuronal populations. In particular, its robust ability to prevent lesion-induced and spontaneous age-related basal forebrain cholinergic neuronal degeneration, and to promote mnemonic recovery, has suggested its potential use as a therapeutic agent in Alzheimer's disease. When infused intracerebroventricularly, however, NGF is associated with several adverse effects that make this delivery route impractical. The present study examined whether intraparenchymal infusions of NGFadjacent to cholinergic neuronal soma are an effective and well-tolerated means of providing NGF to degenerating cholinergic neurons. Cholinergic neuronal rescue together with axonal sprouting responses and local tissue damage in the brain were assessed in adult rats that underwent complete unilateral fornix transections, followed by intraparenchymal infusions of recombinant human NGF for a 2-week period. Intraparenchymal NGF infusions preventedthe degeneration of 94.7 +/- 6.6% of basal forebrain cholinergic neurons compared to 21.7 +/- 2.6% in vehicle-infused animals (p<0.0001). Cholinergicaxons sprouted toward the intraparenchymal NGF source in an apparent gradient-dependent manner. Glial responses to intraparenchymal infusions were minimal, and no apparent toxic effects of the infusions were observed. Thus, when infused intraparenchymally, NGF rescues basal forebrain cholinergic neurons, alters the topography of axonal sprouting responses, and does not induce adverse affects over a 2-week infusion period. intraparenchymal NGF delivery merits further study at longer term time points as a means of treating the cholinergic component of neuronal loss in Alzheimer's disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 18:29:02