A DISTINCT PATTERN OF TROPHIC FACTOR EXPRESSION IN MYELIN-DEFICIENT NERVES OF TREMBLER MICE - IMPLICATIONS FOR TROPHIC SUPPORT BY SCHWANN-CELLS

Distal to a peripheral nerve transection, myelin degradation and Schwa nn cell (SC) proliferation are accompanied by a marked upregulation of brain-derived neurotrophic factor (BDNF) and a decrease of ciliary ne urotrophic factor (CNTF) in non-neuronal cells, To investigate the rol e of SC differentiation in trophic factor regulation, we studied BDNF and CNTF expression in sciatic nerves from Trembler-J (Tr-J) mice. In these animals, a mutation in the pmp-22 gene causes a failure of myeli nation and continuous SC proliferation, but axonal continuity is prese rved. In spite of the severe abnormalities in Tr-J nerves, BDNF levels remained as low as in the intact controls, Thus, the primary SC disor der in Tr-J produces a different pattern of BDNF expression from that caused by axonal breakdown due to nerve transection. Furthermore, the upregulation of BDNF mRNA' triggered by transection was 70-fold in con trol nerves, but only 30-fold in Tr-J sciatic nerves, Because these re sults raised the possibility that axonal loss may influence neurotroph in expression only in SCS that have differentiated toward a myelinatin g phenotype, we measured BDNF mRNA after axotomy in the cervical sympa thetic trunk (CST), a predominantly unmyelinated autonomic nerve. In c ontrast to the sciatic nerves, the BDNF mRNA level barely increased in the injured CST, supporting the idea that not all SCs are equal sourc es of trophic molecules, In Tr-J sciatic nerves, CNTF mRNA levels were fourfold lower than normal, implying that the downregulation of this cytokine is a sensitive indicator of a spectrum of SC perturbations th at affect myelinating cells.