ECTOPIC SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE-IMMUNOREACTIVE FIBERS IN THE SPINAL-CORD OF TRANSGENIC MICE OVER-EXPRESSING NERVE GROWTH-FACTOR

The aim of this study was to investigate the in vivo effects of CNS ov er-expression of nerve growth factor (NGF) on primary sensory neurons. To achieve this objective a transgenic mouse model was generated whic h bore a chick NGF gene driven by the myelin basic protein promoter. N orthern blot analysis demonstrated that high levels of NGF mRNA were d etected in the spinal cord of adult transgenic mice. Using immunocytoc hemistry NGF-immunoreactive (IR) oligodendrocytes were observed throug hout the white matter. Furthermore, numerous ectopic substance P (SP)- and calcitonin gene-related peptide (CGRP)-IR fibres were detected in the white matter of the spinal cord of transgenic mice. NGF-IR oligod endrocytes and ectopic SP- and CGRP-fibres were entirely absent from c ontrol mice. In the cervical and lumbar dorsal root ganglia, the perce ntages of SP-IR neurons were significantly higher in transgenic mice w hen compared with controls. At the electron microscope level, ectopic SP- and CGRP-IR fibres were characterized as unmyelinated axons and ax onal boutons. SP colocalized with CGRP in some of those axonal boutons and fibres. Capsaicin treatment of adult mice completely abolished th e ectopic SP-IR fibres, confirming their primary sensory origin. Our r esults indicate that primary sensory neurons are responsive to NGF ove r-expression in the CNS. Ectopic SP- and CGRP-IR fibres in the white m atter are likely to represent collateral sprouts of the central proces ses of the dorsal root ganglion cells which were triggered by NGF over -expressed in the myelinating oligodendrocytes in the spinal cord of t ransgenic mice.