Leukodystrophy Scientific Publications

Latest publication 01/11/2014

Mice with a deletion of the major central myelin protein exhibit hypersensitivit

mutations in the gene encoding the major myelin protein of the central nervous system, proteolipid protein 1 (PLP1), cause an X-linked form of...

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    [title] => Mice with a deletion of the major central myelin protein exhibit hypersensitivit
    [paragraph] => Mice with a deletion of the major central myelin protein exhibit hypersensitivity to noxious thermal stimuli: involvement of central sensitization
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Authors
B. Petita, F. Giraudetb, C. Béchona, L. Bardinf, P. Avan et al.

 Lab
Université d'Auvergne, Clermont-Ferrand, France
Journal
Neurobiology of Disease
Abstract
 mutations in the gene encoding the major myelin protein of the central nervous system, proteolipid protein 1 (PLP1), cause an X-linked form of spastic paraplegia (SPG2) associated with axonal degeneration. While motor symptoms are the best known manifestations of this condition, its somatosensory disturbances have been described but poorly characterized. We carried out a longitudinal study in an animal model of SPG2 — mice carrying a deletion of the Plp1 gene (Plp- mice). Plp- mice exhibited severe early-onset thermal hyperalgesia, in the absence of thermal allodynia. We first performed an electrophysiological testing which showed an early decrease in peripheral and spinal conduction velocities in Plp  mice. Such as the abnormal sensitive behaviors, this slowing of nerve conduction was observed before the development of myelin abnormalities at the spinal level, from 3 months of age, and without major morphological defects in the sciatic nerve. To understand the link between a decrease in nerve velocity and an increased response to thermal stimuli before the appearance of myelin abnormalities, we focused our attention on the dorsal horn of the spinal cord, the site of integration of somatosensory information. Immunohistochemical studies revealed an early-onset activation of astrocytes and microglia that worsened with age, associated later in age with perturbation of the expression of the sensory neuropeptides calcitonin-gene-related peptide and galanin. Taken together, these results represent complementary data supporting the hypothesis that Plp- mice suffer from ganglionopathy associated with late onset central demyelination but with few peripheral nerve alterations, induced by the glial-cell-mediated sensitization of the spinal cord. The mechanism suggested here could underlie pain experiments in other leukodystrophies as well as in other non-genetic demyelinating diseases such as multiple sclerosis.
BIOSEB Instruments Used
Cold Hot Plate Test (BIO-CHP),Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT)
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For testing animal's thermal sensitivity to pain resulting from exposure to heat or cold: the Cold Hot Plate is an innovative instrument opening new investigation fields for your analgesia and nociception research, and a useful tool for analgesic drug screening using rats or mice models.

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An operator independent test to study pain thresholds in rodents (mouse and rat) by assessing temperature preference (thermal comfort zone) - a new tool for your analgesia/nociception research opening new fields of investigation, and an ideal solution for nociceptive and analgesic drugs screening. Now comes with a brand new software, allowing tracking activity and faster temperature transitions!

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