Opposite effects of axon damage on heat shock proteins (hsp 70) and ubiquitin contents in motor neurons of neuropathic rats.
Alteration in the motoneurone contents of heat shock protein (hsp 70) and ubiquitin were studied in rats which had been subject to loose ligation of one common sciatic nerve. This results in a unilateral peripheral neuropathy which peaks at 14 days following ligation and is characterized by transient degeneration of both myelinated and unmyelinated nerve fibres, abnormal motor behaviours (posture of the hind limb, walking patterns) and thermal and mechanical allodynia of the hind paw. Hsp 70 and ubiquitin are proteins involved in protein metabolism and their expression is regulated during cellular stress. The contralateral unlesioned side was used as control. Motoneurone staining for hsp 70 and ubiquitin were differentially altered at the peak of the neuropathy. Axon damage resulted in a decrease in hsp 70 labeling while ubiquitin staining increased. At the same time motoneurones undergoing axon damage overstained for the immediate early gene encoded protein c-JUN and for nerve growth factor receptor (rNGF). In contrast, no clear alteration was seen, at that time, in the intensity of labeling for calcitonin gene-related peptide (CGRP). This study demonstrates that peripheral neuropathy resulting from loose ligation of the common sciatic nerve not only produces sensory alterations as previously reported but also leads to pronounced alterations in motoneurone functioning that could partly explain the observed abnormal motor behaviours. Results are discussed in accordance with presumed roles for hsp 70 and ubiquitin in protein metabolism and in relationship with possible interaction with c-JUN and rNGF expressions.
Lantéri-Minet
M
M
Institut National de la Santé et de la Recherche Médicale Unité 161, Paris, France.
Desmeules
J A
JA
Menétrey
D
D
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013194:Staining and Labeling; D014452:Ubiquitins / Q000378:metabolism*
D006360:Heat-Shock Proteins; D016755:Proto-Oncogene Proteins c-jun; D017475:Receptors, Nerve Growth Factor; D014452:Ubiquitins; D015740:Calcitonin Gene-Related Peptide