Neuronal gene expression in aluminum myelopathy.
1. Aluminum administration to susceptible animal species results in neurofilament accumulation in neuronal perikarya and proximal axons. Pathogenetic studies in vivo have shown that aluminum rapidly associates with neuronal chromatin. Whether the effect of aluminum on DNA components plays a role in the production of the neurofibrillary lesion remains unclear. 2. In this study we used Northern analysis and in situ hybridization to evaluate mRNA levels of specific neuronal and glial components in the rabbit spinal cord at various times following aluminum administration. 3. Our results show that (a) all neuronal mRNAs evaluated (neurofilament triplet components, neuronal-specific enolase, and amyloid precursor protein) are markedly decreased, with no decrease in glial fibrillary acidic protein; (b) the effect on neuronal gene expression occurs early and concurrently with the development of the neurofibrillary lesion and reverses rapidly after a single dose of aluminum; and (c) there is a direct correlation between the severity of the neurofibrillary lesion and the decrease in neuronal mRNA levels. 4. We interpret our results to mean that the accumulation of neurofilaments in this model is not due to a selective effect on neurofilament gene expression but may be due to an inhibition of genes coding for components involved in processing of neurofilament proteins.
Parhad
I M
IM
Department of Pathology, University of Calgary, Alberta, Canada.
Krekoski
C A
CA
Mathew
A
A
Tran
P M
PM
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits
D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D000535:Aluminum