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.