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Cited by 151Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolNeurological Disease Mechanisms and Treatments

Stress is critical for LPS-induced activation of microglia and damage in the rat hippocampus

Espinosa-Oliva, A.M., de Pablos, R.M., Villarán, R.F., Argüelles, S., Venero, J.L., Machado, A., Cano, J.·2011·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2009.01.012
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Abstract

The hippocampus is insensitive to strong inflammatory stimulus under normal conditions and one of the most severely affected areas in Alzheimer's disease. We have analyzed the effect of chronic stress for 9 days in the hippocampus unilaterally injected with LPS. In non-stressed rats, LPS injection failed to activate microglia although a subset of degenerating cells in the CA1 area was evident. This effect was not accompanied by loss of Neu-N positive neurons in the CA1 area. In stressed rats, LPS injection had a dramatic effect in activating microglia along with astrogliosis and BDNF mRNA induction. NeuN immunostaining demonstrated a loss of about 50% of CA1 pyramidal neurons under these conditions. Fluoro jade B histochemistry demonstrated the presence of degenerating cells in most of CA1 area. Mechanistically, combination of chronic stress and LPS resulted in prominent activation of MAPKs including JNK, p38 and ERK clearly different from LPS injection in controls. Further, LPS+stress induced a dramatic decrease in phosphorylated levels of both Akt and CREB, which fully supports a consistent deleterious state in the hippocampal system under these conditions. Treatment with RU486, a potent inhibitor of glucocorticoid receptor activation, significantly protected animals against the deleterious effects observed in LPS-stressed animals.

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Crossref · 10.1016/j.neurobiolaging.2009.01.012

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  • Chronically stressed animals injected in the prefrontal cortex or hippocampus with endotoxin displayed exacerbated microglia activation and tissue damage.

    “Chronically stressed animals injected either in the prefrontal cortex (144) or the hippocampus (145) with this endotoxin also displayed exacerbated microglia activation and tissue damage.”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [145]

  • GR signaling is essential for the cross-sensitization between stress and the inflammatory response to LPS.

    “GR signaling was thus proposed to be essential for the cross-sensitization between stress and the inflammatory response to LPS.”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [145]

  • The priming effects of stress on the ensuing immune response could be abated with RU486 or by experimentally maintaining plasma GCs to basal levels in adrenalectomized animals.

    “Interestingly, in these studies the priming effects of stress (regardless of its chronicity) on the ensuing immune response could be abated with RU486 or by experimentally maintaining plasma GCs to basal levels in adrenalectomized animals.”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [145]

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Authors
Espinosa-Oliva, A. M., de Pablos, R. M., Villarán, R. F., Argüelles, S., Venero, J. L., Machado, A., & Cano, J.
Affiliations
Universidad de Sevilla (ES)
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2011-01
Volume
32
Issue
1
Pages
85-102
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2009.01.012
OpenAlex
W2034868284
Cited by
151
References
70
Citations by year
2026: 5 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 17 · 2017: 8 · 2016: 13 · 2015: 16 · 2014: 10 · 2013: 13 · 2012: 9
FWCI
3.62
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
Funders
Junta de Andalucía
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
chronic stress, lipopolysaccharide, microglial activation, hippocampus, CA1 pyramidal neurons, neurodegeneration, astrocyte activation, brain-derived neurotrophic factor, MAPK signaling, JNK, p38 MAPK, ERK, Akt, CREB, glucocorticoid receptor, RU486, Alzheimer's disease, neuroinflammation
MeSH terms
Animals, Arachidonic Acids, Body Weight, Cell Count, Corticosterone, Disease Models, Animal, Fluoresceins, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Glutamate Decarboxylase, Hippocampus, Lipopolysaccharides, Male, Organic Chemicals, Phosphopyruvate Hydratase, Progesterone, RNA, Messenger, Stress, Psychological, Time Factors, Tumor Necrosis Factor-alpha, Rats, Wistar, Microglia, Brain-Derived Neurotrophic Factor, Extracellular Signal-Regulated MAP Kinases, Rats, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type I

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