Cited by 217Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

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Relationship between microglial activation and dopaminergic neuronal loss in the substantia nigra: a time course study in a 6‐hydroxydopamine model of Parkinson’s disease

Marinova‐Mutafchieva, Lilia, Sadeghian, Mona, Broom, Lauren, Davis, John B., Medhurst, Andrew D., Dexter, David T.·2009·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2009.06189.x

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Abstract

Cellular interactions between activated microglia and degenerating neurons in in vivo models of Parkinson’s disease are not well defined. This time course study assesses the dynamics of morphological and immunophenotypic properties of activated microglia in a 6‐hydroxydopamine (6‐OHDA) model of Parkinson’s disease. Neurodegeneration in the substantia nigra pars compacta (SNc) was induced by unilateral injection of 6‐OHDA into the medial forebrain bundle. Activated microglia, identified using monoclonal antibodies: clone of antibody that detects major histocompatibility complex (MHC) class II antigens (OX6) for MHC class II, clone of antibody that detects cell surface antigen‐cluster of differentiation 11b – anti‐complement receptor 3, a marker for complement receptor 3 and CD 68 for phagocytic activity. Activation of microglia in the lesioned SNc was rapid with cells possessing amoeboid or ramified morphology appeared on day 1, whilst antibody clone that detects macrophage‐myeloid associated antigen immunoreactivity was observed at day 3 post‐lesion when there was no apparent loss of tyrosine hydroxylase (TH)+ve dopaminergic (DA) SNc neurons. Thereafter, OX6 and antibody clone that detects macrophage‐myeloid associated antigen activated microglia selectively adhered to degenerating axons, dendrites and apoptotic (caspase 3+ve) DA neurons in the SNc were observed at day 7. This was followed by progressive loss of TH+ve SNc neurons, with the peak of TH+ve cell loss (51%) being observed at day 9. This study suggests that activation of microglia precedes DA neuronal cell loss and neurons undergoing degeneration may be phagocytosed prematurely by phagocytic microglia.

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Authors: Marinova‐Mutafchieva, L., Sadeghian, M., Broom, L., Davis, J. B., Medhurst, A. D., & Dexter, D. T.
Affiliations: Imperial College London (GB)
GlaxoSmithKline (United Kingdom) (GB)
ORCID: Dexter, David T.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2009-07-13
Volume: 110
Issue: 3
Pages: 966-975
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2009.06189.x
OpenAlex: W2112111711
Cited by: 217
References: 52
Citations by year: 2026: 6 · 2025: 7 · 2024: 18 · 2023: 11 · 2022: 11 · 2021: 16 · 2020: 19 · 2019: 16 · 2018: 14 · 2017: 8 · 2016: 10 · 2015: 16 · 2014: 19 · 2013: 16 · 2012: 14
FWCI: 6.20
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: microglial activation, dopaminergic neuron loss, substantia nigra pars compacta, Parkinson's disease, 6-hydroxydopamine, neurodegeneration, phagocytosis, MHC class II, CD68, complement receptor 3, tyrosine hydroxylase, caspase-3, apoptosis, microglia-neuron interaction, time course
MeSH terms: Animals, Disease Models, Animal, Dopamine, Male, Neurons, Parkinson Disease, Secondary, Substantia Nigra, Time Factors, Oxidopamine, Rats, Sprague-Dawley, Microglia, Rats

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Relationship between microglial activation and dopaminergic neuronal loss in the substantia nigra: a time course study in a 6‐hydroxydopamine model of Parkinson’s disease

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