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Cited by 228Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchTryptophan and brain disorders

Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation

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Riazi, Kiarash, Galic, Michael A., Kentner, Amanda C., Reid, Aylin Y., Sharkey, Keith A., Pittman, Quentin J.·2015·The Journal of Neuroscience
DOI 10.1523/jneurosci.4485-14.2015PMC PMC6705378
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Abstract

Peripheral inflammatory diseases are often associated with behavioral comorbidities including anxiety, depression, and cognitive dysfunction, but the mechanism for these is not well understood. Changes in the neuronal and synaptic functions associated with neuroinflammation may underlie these behavioral abnormalities. We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA- and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor α in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.

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  • Other antibiotics such as metronidazole and minocycline can potentially enter the central nervous system and can have direct action on brain and behavior.

    “Other antibiotics such as metronidazole and minocycline can potentially enter the central nervous system and can have direct action on brain and behavior (261) (e.g., microglial inhibition with minocycline; Riazi et al., 2015)”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Riazi et al., 2015

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References 91 · Cited by 228

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Authors
Riazi, K., Galic, M. A., Kentner, A. C., Reid, A. Y., Sharkey, K. A., & Pittman, Q. J.
Affiliations
University of Calgary (CA)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2015-03-25
Volume
35
Issue
12
Pages
4942-4952
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.4485-14.2015
PMC
PMC6705378
OpenAlex
W2140019947
Cited by
228
References
91
Citations by year
2026: 18 · 2025: 17 · 2024: 22 · 2023: 17 · 2022: 22 · 2021: 23 · 2020: 23 · 2019: 24 · 2018: 22 · 2017: 22 · 2016: 12 · 2015: 6
FWCI
11.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Crohn's and Colitis Foundation
  • Crohn's and Colitis Foundation of Canada
  • Savoy Foundation
  • Fondation pour la Recherche Médicale
  • Alberta Innovates
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
microglia, peripheral inflammation, colitis, 2,4,6-trinitrobenzene sulfonic acid, hippocampus, glutamatergic neurotransmission, synaptic plasticity, long-term potentiation, long-term depression, GluR2 subunit, AMPA receptors, NMDA receptor, minocycline, TNF-α, neuroinflammation, comorbid depression and anxiety
MeSH terms
Animals, Colon, Inflammation, Male, Minocycline, Synaptic Transmission, Neuronal Plasticity, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha, Microglia, Long-Term Potentiation, Receptors, AMPA, Excitatory Postsynaptic Potentials, Long-Term Synaptic Depression, Rats, Synaptic Potentials, Miniature Postsynaptic Potentials, CA1 Region, Hippocampal

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