Brain-derived neurotrophic factor-transduced fibroblasts: Production of BDNF and effects of grafting to the adult rat brain

Lucidi‐Phillipi, Carrie A.; Gage, Fred H.; Shults, Clifford W.; Jones, Kevin R.; Reichardt, Louis F.; Kang, Un Jung

doi:10.1002/cne.903540306

Cited by 72Nerve injury and regenerationParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Brain-derived neurotrophic factor-transduced fibroblasts: Production of BDNF and effects of grafting to the adult rat brain

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Lucidi‐Phillipi, Carrie A., Gage, Fred H., Shults, Clifford W., Jones, Kevin R., Reichardt, Louis F., Kang, Un Jung·1995·Journal of Comparative Neurology

DOI 10.1002/cne.903540306PMC PMC2710118

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Abstract

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.

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When induction of parkinsonism by 6-OHDA lesion was followed by BDNF treatment, there seemed to be no recovery of the dopaminergic neuron number in substantia nigra.
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From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [97]

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Ex Vivo Gene Transfer of Brain‐derived Neurotrophic Factor to the Intact Rat Forebrain: Neurotrophic Effects on Cholinergic Neurons
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Authors: Lucidi‐Phillipi, C. A., Gage, F. H., Shults, C. W., Jones, K. R., Reichardt, L. F., & Kang, U. J.
Affiliations: University of California San Diego (US)
United States Department of Veterans Affairs (US)
University of California, San Francisco (US)
University of Chicago (US)
Corresponding author: Kang, Un Jung
ORCID: Gage, Fred H.
Jones, Kevin R.
Reichardt, Louis F.
Kang, Un Jung
Venue: Journal of Comparative Neurology
Publisher: Wiley
Published: 1995-04-10
Volume: 354
Issue: 3
Pages: 361-376
ISSN: 0021-9967 (ISSN-L)
1096-9861
DOI: 10.1002/cne.903540306
PMC: PMC2710118
OpenAlex: W2156509631
Cited by: 72
References: 58
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2014: 1 · 2013: 1 · 2012: 1
FWCI: 3.20
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3471 d)
Locations: The Journal of Comparative Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (P01AG010435, R37AG008514, 5R37 AG08514, 5P01 AG10435, AG-00408, T32AG000216)
National Institute of Neurological Disorders and Stroke (P01NS016033)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords: brain-derived neurotrophic factor, cell transplantation, dopaminergic neurons, cholinergic neurons, substantia nigra, striatum, 6-hydroxydopamine lesion, homovanillic acid, nerve growth factor, dorsal root ganglion neurons, mesencephalic neurons, tyrosine hydroxylase
MeSH terms: Animals, Cells, Cultured, Chick Embryo, Fibroblasts, Genetic Engineering, Humans, Nerve Growth Factors, Nerve Tissue Proteins, Rats, Inbred F344, Transcription, Genetic, Protein Biosynthesis, Blotting, Northern, Brain-Derived Neurotrophic Factor, Rats

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Brain-derived neurotrophic factor-transduced fibroblasts: Production of BDNF and effects of grafting to the adult rat brain

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