Ciliary neurotrophic factor protects striatal output neurons in an animal model of Huntington disease.
Huntington disease is a dominantly inherited, untreatable neurological disorder featuring a progressive loss of striatal output neurons that results in dyskinesia, cognitive decline, and, ultimately, death. Neurotrophic factors have recently been shown to be protective in several animal models of neurodegenerative disease, raising the possibility that such substances might also sustain the survival of compromised striatal output neurons. We determined whether intracerebral administration of brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, or ciliary neurotrophic factor could protect striatal output neurons in a rodent model of Huntington disease. Whereas treatment with brain-derived neurotrophic factor, nerve growth factor, or neurotrophin-3 provided no protection of striatal output neurons from death induced by intrastriatal injection of quinolinic acid, an N-methyl-D-aspartate glutamate receptor agonist, treatment with ciliary neurotrophic factor afforded marked protection against this neurodegenerative insult.
Anderson
K D
KD
Regeneneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
Panayotatos
N
N
Corcoran
T L
TL
Lindsay
R M
RM
Wiegand
S J
SJ
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D016923:Cell Death / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000473:pathology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D020933:Neurotrophin 3; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011994:Recombinant Proteins; D017378:Quinolinic Acid