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Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF
Author(s) -
Frim D. M.,
Simpson J.,
Uhler T. A.,
Short M. P.,
Bossi S. R.,
Breakefield X. O.,
Isacson O.
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490350413
Subject(s) - excitotoxicity , neurodegeneration , blockade , glutamate receptor , neurotrophin , nerve growth factor , neurotrophic factors , neuronal degeneration , degeneration (medical) , neuroscience , glial cell line derived neurotrophic factor , mitochondrion , neuroprotection , huntington's disease , biology , pharmacology , endocrinology , medicine , receptor , microbiology and biotechnology , disease , pathology
Consistent with the notion that a defect in cellular energy metabolism is a cause of human neurodegenerative disease, systemic treatment with the mitochondrial complex II inhibitor 3‐nitropropionic acid (3‐NPA) can model the striatal neurodegeneration seen in Huntington's disease. Previously, we have found that nerve growth factor (NGF), delivered biologically by the implantation of a genetically altered fibroblast cell‐line, can protect locally against striatal degeneration induced by infusions of high doses of glutamate receptor agonists. We now report that implantation of NGF‐secreting fibroblasts reduces the size of adjacent striatal 3‐NPA lesions by an average of 64%. We conclude that biologically delivered NGF protects neurons against excitotoxicity and mitochondrial blockade—both energy‐depleting processes—implying that appropriate neurotrophic support in the adult brain could protect against neurodegenerative diseases caused in part by energy depletion. © 1993 Wiley‐Liss, Inc.