Chronic Stress Enhances Microglia Activation and Exacerbates Death of Nigral Dopaminergic Neurons under Conditions of Inflammation

de Pablos, Rocío M; Herrera, Antonio J; Espinosa-Oliva, Ana M; Sarmiento, Manuel; Muñoz, Mario F; Machado, Alberto; Venero, José L

doi:10.1186/1742-2094-11-34

Cited by 201Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Chronic Stress Enhances Microglia Activation and Exacerbates Death of Nigral Dopaminergic Neurons under Conditions of Inflammation

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de Pablos, Rocío M, Herrera, Antonio J, Espinosa-Oliva, Ana M, Sarmiento, Manuel, Muñoz, Mario F, Machado, Alberto, Venero, José L·2014·Journal of Neuroinflammation

DOI 10.1186/1742-2094-11-34PMC PMC3941799

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Abstract

BACKGROUND: Parkinson's disease is an irreversible neurodegenerative disease linked to progressive movement disorders and is accompanied by an inflammatory reaction that is believed to contribute to its pathogenesis. Since sensitivity to inflammation is not the same in all brain structures, the aim of this work was to test whether physiological conditions as stress could enhance susceptibility to inflammation in the substantia nigra, where death of dopaminergic neurons takes place in Parkinson's disease. METHODS: To achieve our aim, we induced an inflammatory process in nonstressed and stressed rats (subject to a chronic variate stress) by a single intranigral injection of lipopolysaccharide, a potent proinflammogen. The effect of this treatment was evaluated on inflammatory markers as well as on neuronal and glial populations. RESULTS: Data showed a synergistic effect between inflammation and stress, thus resulting in higher microglial activation and expression of proinflammatory markers. More important, the higher inflammatory response seen in stressed animals was associated with a higher rate of death of dopaminergic neurons in the substantia nigra, the most characteristic feature seen in Parkinson's disease. This effect was dependent on glucocorticoids. CONCLUSIONS: Our data demonstrate that stress sensitises midbrain microglia to further inflammatory stimulus. This suggests that stress may be an important risk factor in the degenerative processes and symptoms of Parkinson's disease.

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Chronic stress exacerbates inflammatory responses in midbrain microglia, suggesting a potential risk factor in the degenerative processes characteristic of Parkinson's disease.
“Chronic stress exacerbates inflammatory responses in midbrain microglia, suggesting a potential risk factor in the degenerative processes characteristic of Parkinson’s disease.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [69]
This sensitization may accelerate disease progression and worsen symptoms in Parkinson's disease.
“This sensitization may accelerate disease progression and worsen symptoms, highlighting the importance of stress management in these patients.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [69]
Effective stress management could potentially slow disease progression and enhance patients' quality of life in Parkinson's disease.
“Effective stress management could potentially slow disease progression and enhance patients’ quality of life [69].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [69]

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Authors: de Pablos, R. M., Herrera, A. J., Espinosa-Oliva, A. M., Sarmiento, M., Muñoz, M. F., Machado, A., & Venero, J. L.
Affiliations: Instituto de Biomedicina de Sevilla (ES)
ORCID: Herrera, Antonio J
Muñoz, Mario F
Venue: Journal of Neuroinflammation
Publisher: Springer Science and Business Media LLC
Published: 2014
Volume: 11
Issue: 1
Pages: 34
ISSN: 1742-2094 (ISSN-L)
DOI: 10.1186/1742-2094-11-34
PMC: PMC3941799
OpenAlex: W2086472415
Cited by: 201
References: 100
Citations by year: 2026: 11 · 2025: 10 · 2024: 17 · 2023: 17 · 2022: 18 · 2021: 21 · 2020: 13 · 2019: 17 · 2018: 23 · 2017: 10 · 2016: 18 · 2015: 20 · 2014: 6
FWCI: 9.37
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Journal of Neuroinflammation (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
Funders: Junta de Andalucía (P09-CTS-5244, P10-CTS-6494)
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, chronic stress, microglial activation, substantia nigra, dopaminergic neuron death, neuroinflammation, lipopolysaccharide, glucocorticoids, stress sensitization, neurodegeneration
MeSH terms: Animals, Corticosterone, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Inflammation, Lipid Peroxides, Male, Nerve Tissue Proteins, Polysaccharides, Stress, Psychological, Substantia Nigra, Cytokines, Cell Death, Rats, Wistar, Microglia, Rats, Nitric Oxide Synthase Type II, Dopaminergic Neurons

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Chronic Stress Enhances Microglia Activation and Exacerbates Death of Nigral Dopaminergic Neurons under Conditions of Inflammation

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