The contribution of ciliary neurotrophic factor receptors to adult motor neuron survival in vivo is specific to insult type and distinct from that for embryonic motor neurons.

Abstract

Exogenous ciliary neurotrophic factor (CNTF) promotes motor neuron (MN) survival following trauma and in genetic models of MN disease. Unconditional disruption of the mouse CNTF receptor α (CNTFRα) gene leads to MN loss, demonstrating a developmental role for endogenous CNTF receptor signaling. These data also suggest that CNTF receptors may promote adult MN survival and that appropriately manipulating the receptors could effectively treat adult MN disorders. This effort would greatly benefit from a better understanding of the roles played by CNTF receptors in adult MNs. We have previously found that adult onset disruption of CNTFRα in facial MNs of "floxed CNTFRα" mice by AAV-Cre vector injection leads to significantly more MN loss than in identically treated controls. While indicating that CNTF receptors can promote adult MN survival, the data did not distinguish between potential roles in MN maintenance versus roles in protecting MNs from the injection associated trauma or the toxicity of the chronic Cre recombinase (Cre) produced by the AAV-Cre. Here we used an inducible Cre gene construct to produce adult-onset CNTFRα disruption in facial MNs without the traumatic and toxic effects of the AAV-Cre procedure. The MNs survive without CNTFRα, even when challenged by facial nerve crush or the injection-associated trauma, thereby suggesting, in conjunction with our previous study, that endogenous CNTF receptor signaling can protect MNs against toxic insult, such as that produced by chronic Cre. The data also indicate that in vivo CNTF receptors play very different roles in adult and embryonic MNs.

• Authors: Nancy Lee, Carolyn E Rydyznski, Rachel P Spearry, Rachel Robitz, A John Maclennan
• Journal: The Journal of comparative neurology (J Comp Neurol) Vol. 521 Issue 14 Pg. 3217-25 (Oct 01 2013) ISSN: 1096-9861 [Electronic] United States
• PMID: 23695797 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• Bacterial Proteins
• Ciliary Neurotrophic Factor Receptor alpha Subunit
• Luminescent Proteins
• Selective Estrogen Receptor Modulators
• yellow fluorescent protein, Bacteria
• Tamoxifen

Topics

• Adenoviridae (genetics)
• Analysis of Variance
• Animals
• Bacterial Proteins (genetics, metabolism)
• Cell Count
• Cell Survival (genetics)
• Ciliary Neurotrophic Factor Receptor alpha Subunit (genetics, metabolism)
• Disease Models, Animal
• Facial Nerve Diseases (metabolism, pathology)
• Gene Expression Regulation (genetics, physiology)
• Head Injuries, Penetrating (metabolism, pathology)
• Luminescent Proteins (genetics, metabolism)
• Mice
• Mice, Transgenic
• Motor Neurons (metabolism, pathology)
• Selective Estrogen Receptor Modulators (pharmacology)
• Tamoxifen (pharmacology)