PMID- 8408225 OWN - NLM STAT- MEDLINE DCOM- 19931119 LR - 20220330 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 123 IP - 2 DP - 1993 Oct TI - Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. PG - 455-65 AB - The neurotrophin family includes NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Previous studies have demonstrated that expression of NGF and its low-affinity receptor is induced in nonneuronal cells of the distal segment of the transected sciatic nerve suggesting a role for NGF during axonal regeneration (Johnson, E. M., M. Taniuchi, and P. S. DeStefano. 1988. Trends Neurosci. 11:299-304). To assess the role of the other neurotrophins and the members of the family of Trk signaling neurotrophin receptors, we have here quantified the levels of mRNAs for BDNF, NT-3, and NT-4 as well as mRNAs for trkA, trkB, and trkC at different times after transection of the sciatic nerve in adult rats. A marked increase of BDNF and NT-4 mRNAs in the distal segment of the sciatic nerve was seen 2 wk after the lesion. The increase in BDNF mRNA was mediated by a selective activation of the BDNF exon IV promoter and adrenalectomy attenuated this increase by 50%. NT-3 mRNA, on the other hand, decreased shortly after the transection but returned to control levels 2 wk later. In Schwann cells ensheathing the sciatic nerve, only trkB mRNA encoding truncated TrkB receptors was detected with reduced levels in the distal part of the lesioned nerve. Similar results were seen using a probe that detects all forms of trkC mRNA. In the denervated gastrocnemius muscle, the level of BDNF mRNA increased, NT-3 mRNA did not change, while NT-4 mRNA decreased. In the spinal cord, only small changes were seen in the levels of neutrophin and trk mRNAs. These results show that expression of mRNAs for neurotrophins and their Trk receptors is differentially regulated after a peripheral nerve injury. Based on these results a model is presented for how the different neurotrophins could cooperate to promote regeneration of injured peripheral nerves. FAU - Funakoshi, H AU - Funakoshi H AD - Department of Medical Chemistry, Karolinska Institute, Stockholm, Sweden. FAU - Frisen, J AU - Frisen J FAU - Barbany, G AU - Barbany G FAU - Timmusk, T AU - Timmusk T FAU - Zachrisson, O AU - Zachrisson O FAU - Verge, V M AU - Verge VM FAU - Persson, H AU - Persson H LA - eng GR - AG04418/AG/NIA NIH HHS/United States GR - NS09199/NS/NINDS NIH HHS/United States PT - Comparative Study 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 Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Ciliary Neurotrophic Factor) RN - 0 (Receptors, Growth Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkC) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Axons/chemistry/ultrastructure MH - Brain Chemistry MH - Brain-Derived Neurotrophic Factor MH - In Situ Hybridization MH - Male MH - Membrane Proteins/analysis/genetics MH - Models, Biological MH - Muscles/chemistry/ultrastructure MH - Nerve Growth Factors/analysis/*genetics MH - Nerve Tissue Proteins/analysis/genetics MH - Neurons/chemistry/ultrastructure MH - Neurotrophin 3 MH - RNA, Messenger/*analysis/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Receptor Protein-Tyrosine Kinases/analysis/genetics MH - Receptor, Ciliary Neurotrophic Factor MH - Receptor, trkC MH - Receptors, Growth Factor/analysis/genetics MH - Receptors, Nerve Growth Factor/analysis/*genetics MH - Sciatic Nerve/*chemistry/surgery/ultrastructure MH - Spinal Cord/chemistry/ultrastructure MH - Time Factors PMC - PMC2119843 EDAT- 1993/10/01 00:00 MHDA- 1993/10/01 00:01 PMCR- 1994/04/02 CRDT- 1993/10/01 00:00 PHST- 1993/10/01 00:00 [pubmed] PHST- 1993/10/01 00:01 [medline] PHST- 1993/10/01 00:00 [entrez] PHST- 1994/04/02 00:00 [pmc-release] AID - 94012989 [pii] AID - 10.1083/jcb.123.2.455 [doi] PST - ppublish SO - J Cell Biol. 1993 Oct;123(2):455-65. doi: 10.1083/jcb.123.2.455.