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Brain-derived neurotrophic factor-transd ... grafting to the adult rat brain
Brain-derived neurotrophic factor-transduced fibroblasts: production of BDNF and effects of grafting to the adult rat brain.
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Local delivery of brain-derived neurotrophic factor (BDNF) by genetically modified cells provides the unique opportunity to examine the effects of BDNF on adult dopaminergic and cholinergic neurons in vivo. Primary rat fibroblasts were genetically engineered to produce BDNF. Conditioned media from BDNF-transduced fibroblasts supported embryonic chick dorsal root ganglion neurons as well as rat fetal mesencephalic neurons. BDNF-transduced fibroblasts grafted to the rat brain survived and showed continued mRNA production for at least 2 weeks. The effects of BDNF-transduced fibroblast grafts on the dopaminergic and cholinergic systems were then assessed. BDNF-transduced fibroblasts grafted into the normal intact substantia nigra induced sprouting of tyrosine hydroxylase- and neurofilament-immunoreactive fibers into the graft. Fibroblast grafts implanted into the normal intact striatum and midbrain as well as the 6-hydroxydopamine-lesioned brain did not induce sprouting of dopaminergic fibers; neither did they affect drug-induced rotational behavior. BDNF-transduced fibroblasts did, however, significantly increase the homovanillic acid/dopamine ratio when grafted into the normal midbrain. Following transection of the fimbriafornix, BDNF-transduced fibroblasts grafted into the septum were unable to rescue the septal cholinergic population, as did nerve growth factor-producing fibroblast grafts. Genetically modified fibroblast grafts may provide an effective, localized method of BDNF delivery in vivo to test biological effects of this factor on the central nervous system.
Lucidi-Phillipi CA, Gage FH, Shults CW, Jones KR, Reichardt LF, Kang UJ
The Journal of comparative neurology
1995-04-10 00:00
354
3
361-76
Animals,Blotting, Northern,Brain-Derived Neurotrophic Factor,Cells, Cultured,Chick Embryo,Fibroblasts,Genetic Engineering,Humans,Nerve Growth Factors,Nerve Tissue Proteins,Protein Biosynthesis,Rats,Rats, Inbred F344,Transcription, Genetic,Brain-Derived Neurotrophic Factor,Nerve Growth Factors,Nerve Tissue Proteins
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0627, USA
J. Comp. Neurol.
NIA 5P01 AG10435, NIA 5R37 AG08514, NIA AG00408
0021-9967
10.1002/cne.903540306
589
True
7608327
