Immunocytochemical and Ultrastructural Studies of Upper Motor Neurons in Amyotrophic Lateral Sclerosis

Overview

Journal Acta Neuropathol

Specialty Neurology

Date 1992 Jan 1

PMID 1320322

Citations 12

Authors

S Murayama

T W Bouldin

K Suzuki

Affiliations

Soon will be listed here.

Abstract

The pathological alterations in upper motor neurons were investigated in 27 cases of adult-onset sporadic amyotrophic lateral sclerosis (ALS). No significant cytoskeletal alterations were found in the Betz cells of any of the cases except one, although cytoskeletal pathology was consistently present in lower motor neurons. The one case had severe circumscribed atrophy of the precentral gyrus and, microscopically, had argentophilic intracytoplasmic inclusions in Betz cells and other pyramidal neurons in the primary motor area as eell as in the lower motor neurons. Immunocytochemically these inclusions contained the epitope of phosphorylated neurofilament and ubiquitin and ultrastructurally consisted of granule-associated filaments with neurofilaments. This is the first demonstration of alterations of cytoskeleton and ubiquitination in the giant cells of Betz, an established subset of upper motor neurons in ALS. Thus, although uncommon, cytoskeletal changes can be found in upper motor neurons in some ALS cases.

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References

Murayama S, Ookawa Y, Mori H, Nakano I, Ihara Y, Kuzuhara S . Immunocytochemical and ultrastructural study of Lewy body-like hyaline inclusions in familial amyotrophic lateral sclerosis. Acta Neuropathol. 1989; 78(2):143-52. DOI: 10.1007/BF00688202. View

Murayama S, Mori H, Ihara Y, Bouldin T, Suzuki K, Tomonaga M . Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. Ann Neurol. 1990; 27(2):137-48. DOI: 10.1002/ana.410270208. View

Tomonaga M, Saito M, Yoshimura M, Shimada H, Tohgi H . Ultrastructure of the Bunina bodies in anterior horn cells of amyotrophic lateral sclerosis. Acta Neuropathol. 1978; 42(2):81-6. DOI: 10.1007/BF00690971. View

Pappolla M, Omar R, Saran B . The "normal" brain. "Abnormal" ubiquitinilated deposits highlight an age-related protein change. Am J Pathol. 1989; 135(4):585-91. PMC: 1880028. View

Dickson D, Wertkin A, Kress Y, Ksiezak-Reding H, Yen S . Ubiquitin immunoreactive structures in normal human brains. Distribution and developmental aspects. Lab Invest. 1990; 63(1):87-99. View

Murayama S, Arima K, Nakazato Y, Satoh J, Oda M, Inose T . Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 2. Oligodendroglial cytoplasmic inclusions. Acta Neuropathol. 1992; 84(1):32-8. DOI: 10.1007/BF00427212. View

Haas A, Bright P . The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J Biol Chem. 1985; 260(23):12464-73. View

Manetto V, Sternberger N, Perry G, STERNBERGER L, Gambetti P . Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 1988; 47(6):642-53. DOI: 10.1097/00005072-198811000-00007. View

Murayama S, Bouldin T, Suzuki K . Onion bulb formation in the initial complex of neurons in human dorsal root ganglion: their significance and alterations in amyotrophic lateral sclerosis. Acta Neuropathol. 1991; 82(6):462-70. DOI: 10.1007/BF00293380. View

10.

Murayama S, Inoue K, Kawakami H, Bouldin T, Suzuki K . A unique pattern of astrocytosis in the primary motor area in amyotrophic lateral sclerosis. Acta Neuropathol. 1991; 82(6):456-61. DOI: 10.1007/BF00293379. View

11.

STERNBERGER L, Sternberger N . Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci U S A. 1983; 80(19):6126-30. PMC: 534374. DOI: 10.1073/pnas.80.19.6126. View

12.

Hirano A, Donnenfeld H, Sasaki S, Nakano I . Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 1984; 43(5):461-70. DOI: 10.1097/00005072-198409000-00001. View

13.

BROWNELL B, Oppenheimer D, Hughes J . The central nervous system in motor neurone disease. J Neurol Neurosurg Psychiatry. 1970; 33(3):338-57. PMC: 493478. DOI: 10.1136/jnnp.33.3.338. View

14.

Murayama S, Bouldin T, Suzuki K . Selective sparing of Betz cells in primary motor area in hypoxic-ischemic encephalopathy. Acta Neuropathol. 1990; 80(5):560-2. DOI: 10.1007/BF00294620. View

15.

Lowe J, Aldridge F, Lennox G, Doherty F, Jefferson D, Landon M . Inclusion bodies in motor cortex and brainstem of patients with motor neurone disease are detected by immunocytochemical localisation of ubiquitin. Neurosci Lett. 1989; 105(1-2):7-13. DOI: 10.1016/0304-3940(89)90003-7. View

16.

Okamoto K, Hirai S, Shoji M, Senoh Y, Yamazaki T . Axonal swellings in the corticospinal tracts in amyotrophic lateral sclerosis. Acta Neuropathol. 1990; 80(2):222-6. DOI: 10.1007/BF00308929. View

17.

Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y . Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. Acta Neuropathol. 1988; 75(4):345-53. DOI: 10.1007/BF00687787. View

18.

Kato S, Nakamura H . Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol. 1990; 79(6):584-94. DOI: 10.1007/BF00294235. View

19.

Arima K, Murayama S, Mukoyama M, Inose T . Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions. Acta Neuropathol. 1992; 83(5):453-60. DOI: 10.1007/BF00310020. View

20.

Mori H, Kondo J, Ihara Y . Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science. 1987; 235(4796):1641-4. DOI: 10.1126/science.3029875. View