Ectopic Substance P and Calcitonin Gene‐related Peptide Immunoreactive Fibres in the Spinal Cord of Transgenic Mice Over‐expressing Nerve Growth Factor

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Abstract
The aim of this study was to investigate the in vivo effects of CNS over‐expression of nerve growth factor (NGF) on primary sensory neurons. To achieve this objective a transgenic mouse model was generated which bore a chick NGF gene driven by the myelin basic protein promoter. Northern blot analysis demonstrated that high levels of NGF mRNA were detected in the spinal cord of adult transgenic mice. Using immunocytochemistry NGF‐immunoreactive (IR) oligodendrocytes were observed throughout 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 oligodendrocytes and ectopic SP‐ and CGRP‐ fibres were entirely absent from control mice. In the cervical and lumbar dorsal root ganglia, the percentages of SP‐IR neurons were significantly higher in transgenic mice when compared with controls. At the electron microscope level, ectopic SP‐ and CGRP‐IR fibres were characterized as unmyelinated axons and axonal boutons. SP co‐localized with CGRP in some of those axonal boutons and fibres. Capsaicin treatment of adult mice completely abolished the ectopic SP‐IR fibres, confirming their primary sensory origin. Our results indicate that primary sensory neurons are responsive to NGF over‐expression in the CNS. Ectopic SP‐ and CGRP‐IR fibres in the white matter are likely to represent collateral sprouts of the central processes of the dorsal root ganglion cells which were triggered by NGF over‐expressed in the myelinating oligodendrocytes in the spinal cord of transgenic mice.