Neuronal and glial coexpression of argininosuccinate synthetase and inducible nitric oxide synthase in Alzheimer disease.

HENEKA, Michael; Wiesinger, Heinrich; Dumitrescu-Ozimek, Lucia; Riederer, Peter; Feinstein, Douglas L.; Klockgether, Thomas

doi:10.1093/jnen/60.9.906

Article (Scientific journals)

Neuronal and glial coexpression of argininosuccinate synthetase and inducible nitric oxide synthase in Alzheimer disease.

HENEKA, Michael; Wiesinger, Heinrich; Dumitrescu-Ozimek, Lucia et al.

2001 • In Journal of Neuropathology and Experimental Neurology, 60 (9), p. 906 - 916

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https://hdl.handle.net/10993/60980

DOI
10.1093/jnen/60.9.906

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11556547

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Keywords :

Amyloid beta-Peptides; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD68 antigen, human; Glial Fibrillary Acidic Protein; Peptide Fragments; amyloid beta-protein (1-42); Citrulline; Arginine; NOS2 protein, human; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Argininosuccinate Synthase; Aged; Aged, 80 and over; Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Amyloid beta-Peptides/analysis; Antigens, CD/analysis; Antigens, Differentiation, Myelomonocytic/analysis; Arginine/metabolism; Argininosuccinate Synthase/analysis; Argininosuccinate Synthase/metabolism; Citrulline/metabolism; Encephalitis/metabolism; Encephalitis/pathology; Entorhinal Cortex/enzymology; Entorhinal Cortex/pathology; Frontal Lobe/enzymology; Frontal Lobe/pathology; Glial Fibrillary Acidic Protein/analysis; Hippocampus/enzymology; Hippocampus/pathology; Humans; Neuroglia/chemistry; Neuroglia/enzymology; Neuroglia/pathology; Neurons/chemistry; Neurons/enzymology; Neurons/pathology; Nitric Oxide Synthase/analysis; Nitric Oxide Synthase/metabolism; Peptide Fragments/analysis; Alzheimer disease; Argininosuccinate synthetase; Human brain; L-arginine; L-citrulline; Neuroinflammation; Pathology and Forensic Medicine; Neurology; Neurology (clinical); Cellular and Molecular Neuroscience; General Medicine

Abstract :

[en] The enzyme argininosuccinate synthetase (ASS) is the rate limiting enzyme in the metabolic pathway leading from L-citrulline to L-arginine, the physiological substrate of all isoforms of nitric oxide synthases (NOS). ASS and inducible NOS (iNOS) expression in neurons and glia was investigated by immunohistochemistry in brains of Alzheimer disease (AD) patients and nondemented, age-matched controls. In 3 areas examined (hippocampus, frontal, and entorhinal cortex), a marked increase in neuronal ASS and iNOS expression was observed in AD brains. GFAP-positive astrocytes expressing ASS were not increased in AD brains versus controls, whereas the number of iNOS expressing GFAP-positive astrocytes was significantly higher in AD brains. Density measurements revealed that ASS expression levels were significantly higher in glial cells of AD brains. Colocalization of ASS and iNOS immunoreactivity was detectable in neurons and glia. Occasionally, both ASS-and iNOS expression was detectable in CD 68-positive activated microglia cells in close proximity to senile plaques. These results suggest that neurons and astrocytes express ASS in human brain constitutively, whereas neuronal and glial ASS expression increases parallel to iNOS expression in AD. Because an adequate supply of L-arginine is indispensable for prolonged NO generation, coinduction of ASS enables cells to sustain NO generation during AD by replenishing necessary supply of L-arginine.

Disciplines :

Neurology

Author, co-author :

HENEKA, Michael ; Department of Neurology, University of Bonn, Germany

Wiesinger, Heinrich; Department of Physiological Chemistry, University of Tübingen, Germany

Dumitrescu-Ozimek, Lucia; Department of Neurology, University of Bonn, Germany

Riederer, Peter; Department of Psychiatry, University of Würzburg, Würzburg, Germany

Feinstein, Douglas L.; Department of Anesthesiology, Neuroanesthesia Research, University of Illinois at Chicago, Chicago, IL, United States

Klockgether, Thomas; Department of Neurology, University of Bonn, Germany

External co-authors :

yes

Language :

English

Title :

Neuronal and glial coexpression of argininosuccinate synthetase and inducible nitric oxide synthase in Alzheimer disease.

Publication date :

September 2001

Journal title :

Journal of Neuropathology and Experimental Neurology

ISSN :

0022-3069

Publisher :

American Association of Neuropathologists Inc., England

Volume :

Issue :

Pages :

906 - 916

Peer reviewed :

Peer Reviewed verified by ORBi

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