Skip to main content
Log in

Regional mRNA changes in brain stem motor neurons from patients with amyotrophic lateral sclerosis

  • Original Articles
  • Published:
Molecular and Chemical Neuropathology

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

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.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • Goldberg I. H. and Friedman P. A. (1977) Antibiotics and nucleic acids.Ann. Rev. Biochem. 40, 772–805.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Mann D. M. A. (1982) Nerve cell protein metabolism and degenerative disease.Neuropath. Appl. Neurobiol. 8, 161–176.

    Article  CAS  Google Scholar 

  • Mann D. M. and Yates P. O. (1974) Motor neuron disease: The nature of the pathogenic mechanism.J. Neurol. Neurosurg. Psychiat. 37, 1036–1046.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Raghow R. (1987) Regulation of messenger RNA turnover in eukaryotes.Trends Biochem. Sci. 12, 358–360.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Singer R. H. and Penman S. (1983) Messenger RNA in HeLa cells: Kinetics of formation and decay.J. Mol. Biol. 78, 321–334.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03160014

Index Entries

Navigation