Pathology of the inferior olivary nucleus in patients with multiple system atrophy

Abstract. The inferior olivary nucleus (ION) from nine patients with multiple system atrophy was examined with antibodies against α-synuclein, ubiquitin, synaptophysin, glial fibrillary acidic protein, the Golgi apparatus (GA)-trans-Golgi network (TGN), and microglia/macrophages. As previously reported, there were neuronal loss, gliosis, and α-synuclein-positive cytoplasmic inclusions in neurons and glia. In addition, all neurons with α-synuclein-positive cytoplasmic inclusions contained abnormal profiles of the GA and TGN, which were reduced in size and numbers. This finding suggests a relationship between the pathogenetic mechanisms causing inclusion body formation and abnormalities of the GA-TGN. This study is also consistent with the conclusion that lesions of the ION may not always reflect changes of transsynaptic degeneration secondary to Purkinje cell loss.

[1]  Z. Mourelatos,et al.  The fragmented neuronal Golgi apparatus in amyotrophic lateral sclerosis includes the trans-Golgi-network: functional implications , 1998, Acta Neuropathologica.

[2]  H. Kusaka,et al.  Synaptic pathology of spinal anterior horn cells in amyotrophic lateral sclerosis: An immunohistochemical study , 1994, Journal of the Neurological Sciences.

[3]  Y. Hashizume,et al.  A histometrical and comparative study on Purkinje cell loss and olivary nucleus cell loss in multiple system atrophy , 1991, Journal of the Neurological Sciences.

[4]  M. Graeber,et al.  Cellular pathology of the central nervous system. , 2002 .

[5]  N P Quinn,et al.  Olivopontocerebellar pathology in multiple system atrophy , 1996, Movement disorders : official journal of the Movement Disorder Society.

[6]  N. Quinn,et al.  Multiple system atrophy: A review of 203 pathologically proven cases , 1997, Movement disorders : official journal of the Movement Disorder Society.

[7]  T. Kawanami,et al.  Altered synaptophysin-immunoreactive pattern in human olivary hypertrophy , 1994, Neuroscience Letters.

[8]  M. Eddleston,et al.  Molecular profile of reactive astrocytes—Implications for their role in neurologic disease , 1993, Neuroscience.

[9]  R. Ravid,et al.  Decreased neuronal activity in the nucleus basalis of Meynert in Alzheimer's disease as suggested by the size of the Golgi apparatus , 1994, Neuroscience.

[10]  Z. Mourelatos,et al.  Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis (ALS). Clinical studies in ALS of Guam and experimental studies in deafferented neurons and in beta,beta'-iminodipropionitrile axonopathy. , 1994, The American journal of pathology.

[11]  A. Koeppen,et al.  The neuropathology of olivopontocerebellar atrophy. , 1984, Advances in neurology.

[12]  R. Atkins,et al.  A novel, simple, reliable, and sensitive method for multiple immunoenzyme staining: use of microwave oven heating to block antibody crossreactivity and retrieve antigens. , 1995, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[13]  N. Gonatas,et al.  Fragmentation of the Golgi apparatus of the ballooned neurons in patients with corticobasal degeneration and Creutzfeldt-Jakob disease , 2000, Acta Neuropathologica.

[14]  S. Croul,et al.  An anti-organelle antibody in pathology. The chromatolytic reaction studied with a monoclonal antibody against the Golgi apparatus. , 1988, The American journal of pathology.

[15]  Koeppen Ah,et al.  The neuropathology of olivopontocerebellar atrophy. , 1984 .

[16]  N. Gonatas.  Rous-Whipple Award Lecture. Contributions to the physiology and pathology of the Golgi apparatus. , 1994, The American journal of pathology.

[17]  M. Key,et al.  Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[18]  Peter L. Lantos,et al.  Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome) , 1989, Journal of the Neurological Sciences.

[19]  Hitoshi Takahashi,et al.  α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy , 1998, Neuroscience Letters.

[20]  S. Croul,et al.  Immunocytochemical visualization of the Golgi apparatus in several species, including human, and tissues with an antiserum against MG-160, a sialoglycoprotein of rat Golgi apparatus. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[21]  S. Hirai,et al.  Fundamental Morphological Changes in Human Olivary Hypertrophy , 1992, Acta pathologica japonica.

[22]  W. Paulus,et al.  Ki-M1P as a marker for microglia and brain macrophages in routinely processed human tissues , 2004, Acta Neuropathologica.

[23]  H. Yamaguchi,et al.  Oligodendroglial Microtubular Tangles in Olivopontocerebellar Atrophy , 1990, Journal of neuropathology and experimental neurology.

[24]  N. Gonatas,et al.  The involvement of the neuronal Golgi apparatus and trans-Golgi network in the human olivary hypertrophy , 2000, Journal of the Neurological Sciences.

[25]  N. Gonatas,et al.  Fragmentation of the Golgi apparatus of Betz cells in patients with amyotrophic lateral sclerosis , 1999, Journal of the Neurological Sciences.

[26]  M. Yaspo,et al.  Primate homologues of rat TGN38: primary structure, expression and functional implications. , 1996, Journal of cell science.

[27]  N. Gonatas,et al.  MG-160. A novel sialoglycoprotein of the medial cisternae of the Golgi apparatus [published eeratum appears in J Biol Chem 1989 Mar 5;264(7):4264]. , 1989, The Journal of biological chemistry.

[28]  J. Hauw,et al.  Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis. , 1992, The American journal of pathology.