title: The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease.
abstract: Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) are widely expressed in the vertebrate nervous system and play a central role in mature neuronal function. In vitro BDNF/TrkB signaling promotes neuronal survival and can help neurons resist toxic insults. Paradoxically, BDNF/TrkB signaling has also been shown, under certain in vitro circumstances, to render neurons vulnerable to insults. We show here that in vivo conditional deletion of TrkB from mature motor neurons attenuates mutant superoxide dismutase 1 (SOD1) toxicity. Mutant SOD1 mice lacking motor neuron TrkB live a month longer than controls and retain motor function for a longer period, particularly in the early phase of the disease. These effects are subserved by slowed motor neuron loss, persistence of neuromuscular junction integrity and reduced astrocytic and microglial reactivity within the spinal cord. These results suggest that manipulation of BDNF/TrkB signaling might have therapeutic efficacy in motor neuron diseases.
authors.affiliation: Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Zhai
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Hayworth
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.forename: Rudiger
authors.initials: R
authors.lastname: Klein
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Balice-Gordon
authors.forename: Robert Gordon
authors.initials: RG
authors.lastname: Kalb
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003714:Denervation; D018450:Disease Progression; D045888:Ganglion Cysts / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D002479:Inclusion Bodies / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D019426:Integrases / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D008136:Longevity; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D016472:Motor Neuron Disease / Q000150:complications / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology; D020813:Receptor, trkB / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: C493460:Slc18a3 protein, mouse; D025801:Ubiquitin; D050494:Vesicular Acetylcholine Transport Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020813:Receptor, trkB; C045073:Cre recombinase; D019426:Integrases