RT Journal Article
SR Electronic
T1 Endogenous Ciliary Neurotrophic Factor Is a Lesion Factor for Axotomized Motoneurons in Adult Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6999
OP 7006
DO 10.1523/JNEUROSCI.17-18-06999.1997
VO 17
IS 18
A1 Michael Sendtner
A1 Rudolf Götz
A1 Bettina Holtmann
A1 Hans Thoenen
YR 1997
UL http://www.jneurosci.org/content/17/18/6999.abstract
AB 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-oldpmn 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 pmnmice. 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 inpmn 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.