Abstract
An antisense oligonucleotide (54 mer) from the mRNA to the midsize neurofilament protein (NFM) was labeled with35S on the 3′ end and purified by polyacrylamide gel electrophoresis (PAGE).In situ hybridization was performed on sections from medulla oblongata of patients with amyotrophic lateral sclerosis (ALS). The slides were dipped in photographic emulsion, developed, and stained.
Neurons from both nucleus hypoglossus and nucleus ambiguus showed a marked reduction of silver grains when compared to normal. This indicates a reduction of mRNA, which may precede the reduction of ribosomal RNA and the changes in neurofilament proteins that have been described by several investigators in ALS. It does not settle the question of whether the reduction of mRNA is owing to reduced transcription or increased decay of mRNA.
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References
Bradley W. and Krasin F. (1982) DNA hypothesis of amyotrophic lateral sclerosis, inHuman Motor Neuron Diseases (Rowland L. P., ed.), pp. 493–502, Raven, New York.
Davidson T. J., Hartmann H. A., and Johnson P. C. (1981) RNA content and volume of motor neurons in amyotrophic lateral sclerosis. I. The cervical swelling.J. Neuropath. Exp. Neurol. 40, 32–36.
Davidson T. J. and Hartmann H. A. (1981a) RNA content and volume of motor neurons in amyotrophic lateral sclerosis. II. The lumbar intumescence and nucleus dorsalis.J. Neuropath. Exp. Neurol. 40, 187–192.
Davidson T. J. and Hartmann H. A. (1981b) Base composition of RNA obtained from motor neurons in amyotrophic lateral sclerosis.J. Neuropath. Exp. Neurol. 40, 193–198.
Edstrom J. E. (1964) Microextraction and microelectrophoresis for determination of nucleic acid in isolated cellular units, inMethods in Cell Physiology (Prescott D. M., ed.), pp. 417–447, Academic, New York.
Goldberg I. H. and Friedman P. A. (1977) Antibiotics and nucleic acids.Ann. Rev. Biochem. 40, 772–805.
Hartmann H. A., McMahon S., Sun D. Y., Abbs J. H., and Uemura E. (1989) Neuronal RNA in nucleus ambiguus and nucleus hypoglossus of patients with amyotrophic lateral sclerosis.J. Neuropath. Exp. Neurol. 48, 669–673.
Hartmann H. A. and Tomic S. (1990)Changes in Trigeminal Motor Neurons in ALS and Aging. XIth. Int. Congr. Neuropath., Kyoto, Japan, Abstracts, p. 207.
Koenig H. (1969) Neurobiologic effects of agents which alter nucleic acid metabolism, inMotor Neuron Disease (Norris F. A. and Kurland L. T., eds.), pp. 347–368, Grime and Stratton, New York.
Lloyd R. V., Iacangelo A., Eiden L. E., Cano M., Jin L., and Grimes M. (1989) Chromogranin A and B messenger ribonucleic acids in pituitary and other normal and neoplastic human endocrine tissues.Lab. Invest. 60, 548–556.
Manetto V., Sternberger N. H., Perry G., Sternberger L., and Gambetti P. (1988) Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis.J. Neuropath. Exp. Neurol. 47, 642–653.
Mann D. M. A. (1982) Nerve cell protein metabolism and degenerative disease.Neuropath. Appl. Neurobiol. 8, 161–176.
Mann D. M. and Yates P. O. (1974) Motor neuron disease: The nature of the pathogenic mechanism.J. Neurol. Neurosurg. Psychiat. 37, 1036–1046.
Milosavljevic A., Duello T. M., and Schuler L. A. (1989) In situ localization of two prolactin-related messenger ribonucleic acids to binucleated cells of bovine placentomes.Endocrinology 125, 883–889.
Munoz D. G., Greene C., Perl D. P., and Selkoe D. J. (1988) Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis.J. Neuropath. Exp. Neurol. 47, 9–18.
Myers M. W., Lazzarini R. A., Lee V. M. Y., Schlaepfer W. W. and Nelson D. L. (1987) The human mid-size neurofilament subunit: A repeated protein sequence and the relationship of it’s gene to the intermediate gene family.EMBO J. 6, 1617–1626.
Raghow R. (1987) Regulation of messenger RNA turnover in eukaryotes.Trends Biochem. Sci. 12, 358–360.
Schlaepfer W. W. and Bruce J. (1990) Simultaneous up-regulation of neurofilament proteins during the postnatal development of the rat nervous system.J. Neurosci. Res. 25, 39–49.
Singer R. H. and Penman S. (1983) Messenger RNA in HeLa cells: Kinetics of formation and decay.J. Mol. Biol. 78, 321–334.
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Hartmann, H.A., Sun, D.Y. Regional mRNA changes in brain stem motor neurons from patients with amyotrophic lateral sclerosis. Molecular and Chemical Neuropathology 17, 249–257 (1992). https://doi.org/10.1007/BF03160014
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DOI: https://doi.org/10.1007/BF03160014