Acetylcholinesterase gene expression in axotomized rat facial motoneurons is differentially regulated by neurotrophins: correlation with trkB and trkC mRNA levels and isoforms

J Neurosci. 1998 Dec 1;18(23):9936-47. doi: 10.1523/JNEUROSCI.18-23-09936.1998.


We examined the potential influences of muscle-derived neurotrophins on the acetylcholinesterase (AChE) gene expression of adult rat motoneurons. Seven days after facial nerve transection, both AChE mRNA and enzyme activity levels were markedly reduced in untreated and vehicle-treated facial motoneurons, suggesting positive regulation of motoneuron AChE expression by muscle-derived factors. Because skeletal muscle is a source of neurotrophin-3 (NT-3), NT-4/5, and BDNF, these neurotrophins were individually infused onto the proximal nerve stump for 7 d, beginning at the time of axotomy. The trkB ligands NT-4/5 and BDNF prevented the downregulation of AChE mRNA and enzymatic activity, as determined by in situ hybridization, biochemical assay, and histochemical visualization of enzyme activity. In contrast, NT-3 had limited effects, and NGF was without effect. Because motoneurons normally express both trkB and trkC receptors and the trkC ligand NT-3 is the most abundant muscle-derived neurotrophin, we investigated possible reasons for the limited effects of NT-3. In situ hybridization and reverse transcription-PCR both revealed a downregulation of trkC mRNA in axotomized motoneurons, which contrasted the upregulation of trkB expression. Furthermore, isoforms of trkC were detected carrying insertions within their kinase domains, known to limit certain trkC-mediated signal transduction pathways. Because the changes in trkB and trkC mRNA levels were not significantly altered by neurotrophin infusions, it is unlikely they were induced by loss of muscle-derived neurotrophins. These results demonstrate that NT-4/5 and BDNF stimulate AChE gene expression in motoneurons and support the concept that muscle-derived trkB ligands modulate the cholinergic phenotype of their innervating motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics*
  • Animals
  • Axotomy
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / physiology
  • Facial Nerve / cytology*
  • Gene Expression Regulation, Enzymologic
  • Isomerism
  • Male
  • Motor Neurons / drug effects
  • Motor Neurons / enzymology*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, Ciliary Neurotrophic Factor
  • Receptor, trkC
  • Receptors, Nerve Growth Factor / chemistry
  • Receptors, Nerve Growth Factor / genetics*


  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • RNA, Messenger
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkC
  • Acetylcholinesterase