Brain-derived neurotrophic factor (BDNF) regulates its fulllength TrkB (TrkBFL) receptor. BDNF administration to the brain or spinal cord after injury stimulates neuronal plasticity and brings some improvement of impaired functions, but a prolonged exposure of neurons to BDNF in vitro and BDNF infusions to the brain downregulate TrkBFL protein and reduce its downstream signaling, thus limiting BDNF effectiveness. In our recent study we used AAV-mediated transfer of BDNF transgene to cause long-term delivery of BDNF to isolated spinal cord transected at Th11 – Th12 segments. Three groups of rats were used: intact, spinal PBS (spPBS), and spinal AAV-BDNF (spBDNF) injected. The treatment resulted in substantial improvement of treadmill locomotion at two weeks after spinalization, but its effect weakened in time (7 weeks). The mechanism underlying this effect may arise from decreased abundance and availability of TrkBFL and its truncated forms. To verify it, we compared levels of trkbFL/trkbTK transcripts (qPCR) and evaluated TrkBFL segmental distribution (immunohistochemistry). Both transcripts decreased in the scar and in L1 – L2 segments in spPBS rats, but tended to increase in L1 – L2 in spBDNF rats (p<0.07). In L3 – L6 segments no group differences in transcripts were found. Comparison of TrkBFL and c-Myc labeling of transgene-derived BDNF revealed that: (1) caudally to the transection, TrkBFL was abundant in neurons and white matter oligodendroglia (2) c-Myc (+) or (-) neurons showed comparable intensity of TrkBFL labeling (3) neuronal TrkBFL labeling was higher in segments with BDNF excess. In summary, BDNF overproduction in isolated spinal network does not downregulate TrkB transcripts, either it alters cellular abundance and pattern of TrkBFL segmental expression. Data suggest that other aspects of TrkB-mediated signaling are responsible for weakening of functional effect of BDNF. Supported by S007/PolishGerman/2007/01 grant and EMBO fellowship (for EZ).
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