Further characterization of the effects of brain‐derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons

Richard E. Clatterbuck, Donald L. Price, Vassilis E. Koliatsos

Research output: Contribution to journalArticlepeer-review

Abstract

Neurotrophins and neural cytokines are two broad classes of neurotrophic factors. It has been reported that ciliary neurotrophic factor (CNTF) and brain‐derived neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor neurons. In addition, BDNF is transported retrogradely to α‐motor neurons following injection into the muscle, and patterns of BDNF expressed in spinal cord and muscle suggest a physiological role for this factor in motor neurons. In the present study, we characterize the effects of BDNF on axotomized neonatal facial motor neurons and extend these observations to adult models of motor neuron injury (axotomy‐induced phenotypic injury of lumbar motor neurons). BDNF reduces axotomy‐induced degeneration of neonatal neurons by 55% as determined by Nissl staining (percentage of surviving neurons in vehicle‐treated cases, 25%; in BDNF‐treated cases, 80%). Rescued neurons have an intact organelle structure but appear smaller and slightly chromatolytic on electron microscopic analysis. As demonstrated by intense retrograde labeling with horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve, neurons rescued by BDNF have intact mechanisms of fast axonal transport. CNTF did not appear to have significant effects on neonatal motor neurons, but the lack of efficacy of this factor may be caused by its rapid degradation at the application site. BDNF is not capable of reversing the axotomy‐induced reduction in transmitter markers [i.e., the acetylcholine‐synthesizing enzyme choline acetyl‐transferase (ChAT) or the degrading enzyme acetylcholinesterase (AChE)] in neonatal or adult animals or the axotomy‐induced up‐regulation of the low‐affinity neurotrophin receptor p75NGFR (nerve growth factor receptor) in adult motor neurons. However, BDNF appears to promote the expression of p75NGFR in injured neonatal motor neurons. In concert, the findings of the present study suggest that BDNF can significantly prevent cell death in injured motor neurons. However, this neurotrophin may not be a retrograde signal associated with the induction and/or maintenance of some mature features of motor neurons, particularly their transmitter phenotype. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalJournal of Comparative Neurology
Volume342
Issue number1
DOIs
StatePublished - Apr 1 1994

Keywords

  • cell death
  • cytokines
  • facial nucleus
  • nerve growth factor receptor
  • neurotrophins

ASJC Scopus subject areas

  • Neuroscience(all)

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