title: Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF.
abstract: 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.
authors.affiliation: Neuroregeneration Laboratory, McLean Hospital, Belmont, Massachusetts 02178.
authors.forename: D M
authors.initials: DM
authors.lastname: Frim
authors.forename: J
authors.initials: J
authors.lastname: Simpson
authors.forename: T A
authors.initials: TA
authors.lastname: Uhler
authors.forename: M P
authors.initials: MP
authors.lastname: Short
authors.forename: S R
authors.initials: SR
authors.lastname: Bossi
authors.forename: X O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: O
authors.initials: O
authors.lastname: Isacson
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology; D002460:Cell Line; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects* / Q000648:ultrastructure; D004734:Energy Metabolism / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005818:Genetic Engineering; D007150:Immunohistochemistry; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009410:Nerve Degeneration / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; C015392:3-nitropropionic acid