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Raised Thyrotrophin‐Releasing Hormone, Pyroglutamylamino Peptidase, and Proline Endopeptidase Are Present in the Spinal Cord of Wobbler Mice but Not in Human Motor Neurone Disease
Author(s) -
Court J. A.,
McDermott J. R.,
Gibson A. M.,
Marshall E.,
Bloxham C. A.,
Perry R. H.,
Edwardson J. A.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb09997.x
Subject(s) - spinal cord , endocrinology , medicine , thyrotropin releasing hormone , central nervous system , lumbar spinal cord , medulla oblongata , somatostatin , neurotensin , hormone , neuropeptide , psychiatry , receptor
The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn ceils in the spinal cord and brainstem and subsequent muscle wasting, particularly of the fore‐limbs and neck. The wr mice, 2–3 months of age, were found to have increased levels of immunoreactive‐thyrotrophin‐releasing hormone (ir‐TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive‐somatostatin,‐neurotensin, and‐substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5‐hydroxyindoleacctic acid were also raised in the spinal cord of 2–3‐month‐old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5‐hydroxytrypt‐amine were not. Increased spinal cord levels of ir‐TRH and PGAP and PEP activities were not observed in the 1‐month‐old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir‐TRH, PGAP, or PEP in human motor neurone disease.