BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal neurons in vivo.
Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been identified as survival factors for adult axotomized rat corticospinal neurons (CSN) in vivo. Axotomy of corticospinal neurons at the level of the internal capsule induced death of 46% of the CSN within the first week after axotomy. The surviving population of CSN displayed severe atrophy with mean cross-sectional area 49% of their unlesioned contralateral counterparts 7 days after axotomy. Using in situ hybridization to assess the expression of the receptors for the family of neurotrophins, we found trkB and trkC but not trkA mRNA expression in CSN. Intraparenchymal application of BDNF or NT-3 at doses of 12 microg/day for 7 days via an osmotic minipump fully prevented the axotomy-induced death of CSN. Interestingly, no neuronal atrophy was seen after BDNF application while NT-3 had only a partial effect on the size of the axotomized CSN. Nerve growth factor did not prevent death or cell atrophy, consistent with lack of trkA mRNA expression in these neurons. These findings show that BDNF and NT-3 are survival factors for adult rat CSN in vivo, and may contribute to the development of therapeutic strategies aiming at the prevention of CSN degeneration in human motor neuron diseases.
Giehl
K M
KM
Department of Physiology and Neuroscience Institute, University of Ottawa, Ottawa, Ontario, Canada.
Tetzlaff
W
W
D000818:Animals; D001284:Atrophy; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D020933:Neurotrophin 3; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC