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The Journal of Neuroscience, August 1, 1998, 18(15):5891-5900
Heat Shock Protein 27: Developmental Regulation and Expression after Peripheral Nerve Injury
Michael Costigan1, 2, Richard J. Mannion1, 2, Giles Kendall1, Susan E. Lewis2, Jason A. Campagna2, Richard E. Coggeshall3, Jacqueta Meridith-Middleton1, Simon Tate4, and Clifford J. Woolf1, 2 1 Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom, 2 Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, 3 Department of Anatomy and Neurobiology, University of Texas Medical Branch, Galveston, Texas 77551, and 4 Glaxo-Wellcome Research and Development, Gene Function Unit, Stevenage, Herts SG1 2NY, United Kingdom
The heat shock protein (HSP) 27 is constitutively expressed at low levels in medium-sized lumbar dorsal root ganglion (DRG) cells in adult rats. Transection of the sciatic nerve results in a ninefold upregulation of HSP27 mRNA and protein in axotomized neurons in the ipsilateral DRG at 48 hr, without equivalent changes in the mRNAs encoding HSP56, HSP60, HSP70, and HSP90. Dorsal rhizotomy, injuring the central axon of the DRG neuron, does not upregulate HSP27 mRNA levels. After peripheral axotomy, HSP27 mRNA and protein are present in small, medium, and large DRG neurons, and HSP27 protein is transported anterogradely, accumulating in the dorsal horn and dorsal columns of the spinal cord, where it persists for several months. Axotomized motor neurons also upregulate HSP27. Only a minority of cultured adult DRG neurons are HSP27-immunoreactive soon after dissociation, but all express HSP27 after 24 hr in culture with prominent label throughout the neuron, including the growth cone. HSP27 differs from most axonal injury-regulated and growth-associated genes, which are typically present at high levels in early development and downregulated on innervation of their targets, in that its mRNA is first detectable in the DRG late in development and only approaches adult levels by postnatal day 21. In non-neuronal cells, HSP27 has been shown to be involved both in actin filament dynamics and in protection against necrotic and apoptotic cell death. Therefore, its upregulation after adult peripheral nerve injury may both promote survival of the injured neurons and contribute to alterations in the cytoskeleton associated with axonal growth.
Key words: dorsal root ganglion; axotomy; differential gene expression; apoptosis; spinal cord; regeneration
Copyright © 1998 Society for Neuroscience 0270-6474/98/18155891-10$05.00/0
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