Gene probe for P0 messenger RNA used to index acrylamide toxic neuropathy in rats.
Cumulative exposure to the neurotoxicant acrylamide produces axonal damage in the distal ends of both central (CNS) and peripheral (PNS) nerve fibers and subsequent hind-limb paralysis. The messenger RNA which codes for the PNS myelin glycoprotein P0 (P0-mRNA) was used to monitor this toxic neuropathy in Sprague Dawley rats prior to, concurrent with, and subsequent to, ultrastructurally and immunocytochemically defined nerve damage. Rats were dosed every other day with acrylamide (50 mg/kg, IP) and sampled intermittently throughout a 4 week exposure period. Slot blot and Northern gel analyses of the proximal and distal sciatic nerve were used to determine a quantitated measure of P0-mRNA. Twenty-four hours after the first treatment, in the absence of ultrastructural damage, P0-mRNA increased 55% over control levels in the distal sciatic nerve. After 12 treatments, and concomitant with the appearance of spinal cord and PNS neuropathic damage and hindlimb dysfunction, P0-mRNA decreased 45% below control levels. Levels of P0-mRNA from rats exposed to 12 treatments of acrylamide but allowed to recover for 40 days, returned to 79% of control values to reflect the regeneration and remyelination occurring in the distal sciatic nerve. In spite of these fluctuations in levels of P0-mRNA, immunocytochemical staining of P0 protein in plastic sections of the distal sciatic nerve was present throughout all sample times. These results suggest that changes in neural specific mRNAs are sensitive to neurotoxic damage and can be used to monitor the pathogenesis of nerve degeneration.
Veronesi
B
B
U.S. Environmental Protection Agency, Neurotoxicology Division, Research Triangle Park, Carolina 27711.
Jones
K
K
Gupta
S
S
Pringle
J
J
Mezei
C
C
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000187:drug effects*; D015152:Blotting, Northern; D015342:DNA Probes; D006023:Glycoproteins / Q000235:genetics*; D007124:Immunoenzyme Techniques; D008297:Male; D008854:Microscopy, Electron; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000235:genetics*; D009186:Myelin Sheath / Q000187:drug effects*; D009416:Nerve Regeneration / Q000502:physiology; D009693:Nucleic Acid Hybridization; D010525:Peripheral Nerves / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D000178:Acrylamides; D015342:DNA Probes; D006023:Glycoproteins; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D012333:RNA, Messenger; D020106:Acrylamide