PMID- 8301265 OWN - NLM STAT- MEDLINE DCOM- 19940308 LR - 20220310 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 24 IP - 12 DP - 1993 Dec TI - Influences of neurotrophins on mammalian motoneurons in vivo. PG - 1555-77 AB - Several recently reported investigations have shown that a member of the neurotrophin family of neuronal growth factors, brain-derived neurotrophic factor (BDNF), supports motoneurons in vitro and rescues motoneurons from naturally occurring and axotomy-induced cell death (Oppenheim et al., 1992b; Sendtner et al., 1992b; Yan et al., 1992; Koliatsos et al., 1993; Henderson et al., 1993). In the current study, we have explored the issue of whether BDNF and other neurotrophins act to regulate motoneuron survival during development and asked whether synthesis of motoneuron transmitter enzymes is also regulated. We first examined whether spinal motoneurons in newborn animals could retrogradely transport iodinated neurotrophins from their targets in a specific, receptor-mediated manner. We found that motoneurons readily transported NGF, BDNF, and neurotrophin-3 (NT-3). The retrograde transport of one factor could be completely or largely blocked by excess of unlabeled homologous factor, but only partially blocked by excess of unlabeled heterologous factors. Since previous studies have shown that these three neurotrophins bind to the low-affinity NGF receptor, p75NGFR, with similar affinity, our data suggest that the retrograde transport of neurotrophins by motoneurons may be mediated by additional components, such as the trk family of proto-oncogenes. Consistent with this hypothesis, we demonstrate here that motoneurons express mRNA for two members of the trk family, trkB and trkC. Furthermore, both trkB and trkC were expressed by E13, consistent with a role for BDNF and NT-3 in regulating important developmental events involving motoneurons such as naturally occurring cell death. In order to determine which members of the neurotrophin family influence motoneuron survival and to assess the generality of their effects, we evaluated the abilities of NGF, BDNF, and NT-3 to save both spinal and cranial motoneurons after neonatal axotomy. Locally applied BDNF saved 40-70% of motoneurons which would ordinarily die after axotomy in lumbar and cranial motor pools, depending on the treatment protocol employed. NT-3 also exhibited some ability to rescue motoneurons and saved 20-25% of motoneurons which would die in the absence of treatment. Finally, we asked whether neurotrophins could influence synthesis of transmitter enzymes by motoneurons as well as their survival after axotomy. Locally applied BDNF and NT-3 could partially prevent the decrease of protein contents in L4 and L5 ventral roots which normally follows sciatic nerve transection. However, treatment with these neurotrophins did not prevent the decrease in choline acetyltransferase (ChAT) activity in L4 and L5 ventral roots which results from this procedure.(ABSTRACT TRUNCATED AT 400 WORDS) FAU - Yan, Q AU - Yan Q AD - Department of Neurobiology, Amgen, Inc., Thousand Oaks, California 91320. FAU - Elliott, J L AU - Elliott JL FAU - Matheson, C AU - Matheson C FAU - Sun, J AU - Sun J FAU - Zhang, L AU - Zhang L FAU - Mu, X AU - Mu X FAU - Rex, K L AU - Rex KL FAU - Snider, W D AU - Snider WD LA - eng GR - NS31768/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Iodine Radioisotopes) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) SB - IM GS - trkB GS - trkC MH - Animals MH - Animals, Newborn/metabolism MH - Biological Transport/physiology MH - Brain-Derived Neurotrophic Factor MH - Cell Survival/drug effects MH - Chick Embryo MH - Choline O-Acetyltransferase/biosynthesis/drug effects MH - Ganglia, Spinal/cytology/metabolism MH - Gene Expression MH - Iodine Radioisotopes MH - Motor Neurons/*drug effects MH - Nerve Growth Factors/pharmacokinetics/*pharmacology MH - Nerve Tissue Proteins/pharmacokinetics/*pharmacology MH - Neurotrophin 3 MH - Proto-Oncogenes MH - Rats EDAT- 1993/12/01 00:00 MHDA- 1993/12/01 00:01 CRDT- 1993/12/01 00:00 PHST- 1993/12/01 00:00 [pubmed] PHST- 1993/12/01 00:01 [medline] PHST- 1993/12/01 00:00 [entrez] AID - 10.1002/neu.480241202 [doi] PST - ppublish SO - J Neurobiol. 1993 Dec;24(12):1555-77. doi: 10.1002/neu.480241202.