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Ex Vivo Gene Transfer of Brain‐derived Neurotrophic Factor to the Intact Rat Forebrain: Neurotrophic Effects on Cholinergic Neurons
Author(s) -
MartinezSerrano Alberto,
Hantzopoulos Petros A.,
Björklund Anders
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01258.x
Subject(s) - neurotrophic factors , choline acetyltransferase , cholinergic neuron , nucleus basalis , cholinergic , neuroscience , biology , neurotrophin , brain derived neurotrophic factor , forebrain , nerve growth factor , basal forebrain , glial cell line derived neurotrophic factor , microbiology and biotechnology , medicine , endocrinology , central nervous system , receptor , biochemistry
Neurotrophic effects of human brain‐derived neurotrophic factor (hBDNF) on forebrain cholinergic neurons were addressed after ex vivo gene transfer to the intact adult rat brain, using a conditionally immortalized neural progenitor cell line (CINP) engineered to secrete the neurotrophin (2.8 ng/h/106 cells). This cell line was derived by repeated retroviral infection of the parental neural precursor line HiB5 followed by subcloning. The cells survived well in the host brain for long periods of time (up to 4 weeks), and induced a hypertrophic response of cholinergic neurons (positive for acetylcholinesterase, choline acetyltransferase or low‐affinity nerve growth factor receptor) in the nucleus basalis magnocellularis and striatum. We conclude that these cholinergic cell groups are responsive to a low‐level supply (nanograms per day) of BDNF in vivo when the neurotrophin is administered locally in the vicinity of the cell bodies.