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. 2024 Nov;50(1):312-313.
doi: 10.1038/s41386-024-01921-3.

Rewiring the brain: Inflammation's impact on glutamate and neural networks in depression

Ebrahim Haroon  1 , Andrew H Miller  2
Affiliations

Rewiring the brain: Inflammation's impact on glutamate and neural networks in depression

Ebrahim Haroon et al. Neuropsychopharmacology. 2024 Nov.

Erratum in

No abstract available

PubMed Disclaimer

Conflict of interest statement

EH denies the presence of competing interests or conflicts. AHM is a paid consultant for Cerevel Therapeutics, Sirtsei Pharmaceuticals Inc., and Freedom Biosciences.

Figures

Fig. 1
Fig. 1. Inflammation, Glutamate, and Glia in Neural Circuit Dysfunction.
Illustration of the cascade of events leading from peripheral immune activation to corticostriatal network dysfunction and behavioral changes. 1. Blood-brain barrier (BBB) permeability: Peripheral immune cells, including neutrophils and leukocytes, and immune molecules, such as cytokines, infiltrate the brain through increased permeability of the BBB. 2. Reactive astrocytes and activated microglia: Within the brain, infiltrating immune cells interact with resident glial cells, leading to the activation of astrocytes and microglia. Activated microglia and reactive astrocytes release proinflammatory cytokines such as TNF, iNOS, IL-1beta, IL-6, IL-12, and IL-23). 3. Pro-inflammatory cytokines: These cytokines propagate an inflammatory response that can affect healthy neurons. 4. Neuronal impact and outcome: Proinflammatory cytokines lead to an increased release of glutamate into the synapse and decreased clearance from the synapse, leading to extrasynaptic spillover and activation of extrasynaptic NMDA receptors in neurons. Extrasynaptic glutamate manifests as selective damage and dysfunction of neurons, particularly affecting corticostriatal networks, which are crucial for affective and executive cognitive functions and various neurological and psychiatric disorders. (Adapted from “Role of Astrocytes and Microglia in Neurodegeneration”, by BioRender.com (2024). Retrieved from https://app.biorender.com/biorender-templates). BBB Blood-brain barrier, TNF-α Tumor Necrosis Factor-alpha, iNOS Inducible Nitric Oxide Synthase, IL Interleukin, NMDA N-Methyl-D-Aspartate.
See this image and copyright information in PMC

References

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