Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains

Imamura, Kazuhiro; Hishikawa, Nozomi; Sawada, Makoto; Nagatsu, Toshiharu; Yoshida, Mari; Hashizume, Yoshio

doi:10.1007/s00401-003-0766-2

Cited by 791Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains

Imamura, Kazuhiro, Hishikawa, Nozomi, Sawada, Makoto, Nagatsu, Toshiharu, Yoshida, Mari, Hashizume, Yoshio·2003·Acta Neuropathologica

DOI 10.1007/s00401-003-0766-2

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Abstract

There are numerous observations confirming that microglia expressing major histocompatibility complex (MHC) class II molecules are associated with the central nervous system (CNS) in aging and pathological conditions. In this study, we investigated the distribution of MHC class II-positive microglia in Parkinson's disease (PD) brains. The number of MHC class II-positive microglia in the substantia nigra (SN) and putamen increased as the neuronal degeneration of the SN proceeded. These cells were also ICAM-1 (CD54) and LFA-1 (CD11a) positive. The number of activated microglia not only in the SN and putamen but also in the hippocampus, transentorhinal cortex, cingulate cortex and temporal cortex in PD was significantly higher than that in the normal control. Most activated microglia persisted regardless of the presence or absence of Lewy bodies. They were frequently associated not only with alpha-synuclein-positive Lewy neurites, but also with TH-16-positive dopaminergic and WH-3-positive serotonergic neurites, as well as MAP-2- and SMI-32-positive neurites. These activated microglia were also positive for TNF-alpha and interleukin-6, which are known to have a neuroprotective function. We conclude that MHC class II-positive microglia are a sensitive index of neuropathological change and are actively associated with damaged neurons and neurites.

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Reactive microglia characterized by amoeboid-shaped morphology are associated with α-syn pathology in the SN and hippocampus of PD patients.
“Subsequent investigations of postmortem brain tissue from PD patients revealed that reactive microglia, characterized by amoeboid-shaped morphology, were associated with α-syn pathology in the SN and hippocampus.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [220]

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Authors: Imamura, K., Hishikawa, N., Sawada, M., Nagatsu, T., Yoshida, M., & Hashizume, Y.
Affiliations: Okazaki City Hospital (JP)
Nagoya University (JP)
Fujita Health University (JP)
Aichi Medical University (JP)
Corresponding author: Imamura, Kazuhiro
ORCID: Hishikawa, Nozomi
Sawada, Makoto
Nagatsu, Toshiharu
Yoshida, Mari
Hashizume, Yoshio
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2003-12-01
Volume: 106
Issue: 6
Pages: 518-526
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-003-0766-2
OpenAlex: W2001176185
Cited by: 791
References: 54
Citations by year: 2026: 35 · 2025: 49 · 2024: 70 · 2023: 49 · 2022: 76 · 2021: 56 · 2020: 62 · 2019: 46 · 2018: 34 · 2017: 36 · 2016: 30 · 2015: 35 · 2014: 37 · 2013: 26 · 2012: 29
FWCI: 4.39
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords: Parkinson's disease, microglial activation, substantia nigra, putamen, ICAM-1, LFA-1, Lewy bodies, alpha-synuclein, TNF-α, interleukin-6, neuroinflammation, neuroprotection
MeSH terms: Aged, Aged, 80 and over, Brain, Female, Genes, MHC Class II, Humans, Immunohistochemistry, Male, Nerve Tissue Proteins, Parkinson Disease, Blotting, Western, Cytokines, Neurites, Microglia, Synucleins, alpha-Synuclein

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Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains

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