Trophic dependencies of rodent corticospinal neurons.
According to the classical neurotrophin hypothesis, neuronal survival is regulated by limited access to target-derived neurotrophic substances. Recent studies have indicated that this regulation is more complex than originally thought. First, neurons are not only supported by target-derived molecules but also via anterograde, paracrine, and autocrine mechanisms. Second, phenotypes of neurotrophic factor-/receptor-mutant animals displayed fewer neuronal deficits than predicted, suggesting interactivity and redundancy of trophic support of neurons. Finally, certain neurotrophins, in addition to their survival-promoting action, are able to induce neuronal death. Observations in the corticospinal system support the general applicability of these concepts and provide additional insights into the integrative mode of neuronal survival regulation. CNTF and GDNF support developing corticospinal neurons (CSN) by direct mechanisms, while the effects of NT-4/5 require cell contacts of CSN with other cortical neurons in vitro. Thus, these effects do not merely reflect trophic redundancy but the ability of CSN to integrate survival signals of growth factors from different families via different pathways. CNTF and GDNF also promote survival of adult axotomized CSN in vivo. Virtually all adult CSN express mRNA coding for the NT-3-receptor TrkC and the BDNF-receptor TrkB, and after axotomy, CSN also express mRNA for the common neurotrophin-receptor p75NTR, suggesting a role of endogenous neurotrophins for survival regulation of CSN. Indeed, most axotomized CSN depend on endogenous BDNF for survival, and endogenous NT-3 promotes the death of BDNF-dependent CSN. NT-3-mediated death-induction requires co-signalling of TrkC- and p75NTR-receptors. With BDNF/TrkB promoting survival and NT-3/TrkC/p75NTR promoting death, CSN integrate at least three different neurotrophin/receptor-signals for death/survival decisions.
Department of Anatomy, University of Saarland, Homburg/Saar, Germany. k.giehl@rz.uni-sb.de
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D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D051379:Mice; D009044:Motor Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051381:Rats; D012377:Rodentia / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism
D009414:Nerve Growth Factors