NGFR-mRNA expression in sciatic nerve: a sensitive indicator of early stages of axonopathy.
Expression of the low-affinity nerve growth factor receptor (NGFR) in the sciatic nerve (particularly Schwann cells) is high during development but is downregulated upon establishment of the mature axon-Schwann cell relationship. NGFR is re-expressed by Schwann cells if this relationship is altered by degeneration of axons (axotomy) or myelin (tellurium intoxication). To determine the sensitivity of NGFR expression to axonal injury, we have assayed NGFR-mRNA levels in proximal and distal regions of nerves exposed to the axonopathic agents acrylamide and isoniazid, as well as in proximal and distal stumps of axotomized nerves. NGFR-mRNA was elevated in all three models and correlated regionally with sites of axonal perturbation. In distal regions of acrylamide- and isoniazid-intoxicated nerves, NGFR-mRNA was elevated at least 2 days prior to visible signs of axonal degeneration as assayed by morphological techniques utilizing light microscopy. NGFR-mRNA was also elevated in proximal regions of axotomized and acrylamide-intoxicated nerves prior to signs of axonal degeneration. In these models, increased mRNA expression correlated with alterations in the size distribution of axonal cross sections. The common response in all of these situations indicates that NGFR expression, in addition to being a marker for axonal degeneration, is also a sensitive indicator of less profound perturbations in normal axon-Schwann cell interactions, including early stages of axonopathy. We suggest that assay for NGFR-mRNA may be utilized as a rapid and simple method (relative to more labor-intensive morphological methods) to screen for peripheral neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Roberson
M D
MD
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599, USA.
Toews
A D
AD
Bouldin
T W
TW
Weaver
J
J
Goines
N D
ND
Morell
P
P
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000473:pathology*; D015152:Blotting, Northern; D015870:Gene Expression; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012583:Schwann Cells; D012584:Sciatic Nerve / Q000473:pathology*
D000178:Acrylamides; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020106:Acrylamide