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Volume 17, Number 18, Issue of September 15, 1997 pp. 6999-7006
Copyright ©1997 Society for Neuroscience

Endogenous Ciliary Neurotrophic Factor Is a Lesion Factor for Axotomized Motoneurons in Adult Mice

Received April 16, 1997; revised June 19, 1997; accepted July 1, 1997.

Michael Sendtner¹, Rudolf Götz¹, Bettina Holtmann^{1, 2}, and Hans Thoenen²

¹ Clinical Research Unit for Neuroregeneration, Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany, and ² Department of Neurochemistry, Max-Planck-Institut for Psychiatry, D-82152 Martinsried, Germany

Ciliary neurotrophic factor (CNTF) is an abundant cytosolic molecule in myelinating Schwann cells of adult rodents. In newborn animals in which CNTF is not yet expressed, exogenous CNTF that is locally administered very effectively protects motoneurons from degeneration by axotomy. To evaluate whether endogenous CNTF, released after nerve injury from the cytosol of Schwann cells, supports motoneuron survival, we transected the facial nerve in 4-week-old pmn mice. In this mouse mutant a rapidly progressing degenerative disease of motoneurons starts by the third postnatal week at the hindlimbs and progresses to the anterior parts of the body, leading to death by the seventh to eighth week. Apoptotic death of motoneurons can be observed during this period, as revealed by TUNEL staining. In 6-week-old unlesioned pmn mice ~40% of facial motoneurons have degenerated. Facial nerve lesion dramatically increased the number of surviving motoneurons in pmn mice. This protective effect was absent in pmn mice lacking endogenous CNTF. Quantitative analysis of leukemia inhibitory factor (LIF) mRNA expression revealed that the dramatic upregulation seen in wild-type mice after peripheral nerve lesion did not occur in pmn mice. Therefore, endogenous LIF cannot compensate for the lack of CNTF in pmn crossbred with CNTF knock-out mice. Thus, endogenous CNTF released from lesioned Schwann cells supports the survival of axotomized motoneurons under conditions in which motoneurons are in the process of rapid degeneration.

Key words: ciliary neurotrophic factor; leukemia inhibitory factor; CNTF; LIF; motoneurons; facial nucleus; nerve lesion; axotomy; cell death; apoptosis

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