Neuroinflammation and Behavioral Changes in Depression Models

Experimental models of depression increasingly implicate neuroinflammation as a driver of behavioural dysfunction, linking peripheral immune activation to central nervous system pathology. In response to stressors such as lipopolysaccharide administration, chronic social defeat or hormonal manipulation, glial cells—particularly microglia and astrocytes—adopt pro-inflammatory phenotypes, releasing cytokines that disrupt neurotransmitter metabolism and synaptic plasticity. Activation of NF-κB and related inflammatory cascades induces indoleamine 2,3-dioxygenase and perturbs the tryptophan–kynurenine pathway, diminishing serotonin precursors and generating neurotoxic metabolites. Simultaneously, the inflammatory milieu down-regulates brain-derived neurotrophic factor, undermining neuronal resilience and leading to depressive-like behaviours such as anhedonia, immobility and social withdrawal. This mechanistic framework underscores the potential of anti-inflammatory agents, hormone modulators and neuroprotective compounds to restore homeostasis and offers a translational bridge for novel antidepressant strategies.

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Neuroinflammation and Behavioral Changes in Depression Models publication trend

The graph below shows the total number of articles in neuroinflammation and behavioral changes in depression models across all publications each year (not limited to Nature Index journals).

Technical terms

Neuroinflammation: Central nervous system immune response characterised by activation of glial cells and release of inflammatory mediators.

Microglia: Resident immune cells of the brain that mediate inflammatory responses and phagocytosis.

Cytokines: Small signalling proteins released by immune cells to regulate inflammation and cell communication.

NF-κB signalling pathway: Transcriptional mechanism that controls expression of genes involved in immune and inflammatory responses.

Brain-derived neurotrophic factor (BDNF): Neuronal growth factor that supports synaptic plasticity and is implicated in mood regulation.

Indoleamine 2,3-dioxygenase (IDO1): Enzyme that degrades tryptophan into kynurenine, linking immune activation to neurotransmitter imbalance.

Tryptophan–kynurenine (TRP/KYN) pathway: Metabolic cascade converting tryptophan to kynurenine metabolites with neuromodulatory and immunoregulatory effects.

References

1. Latroeggtoxin-VI protects nerve cells and prevents depression by inhibiting NF-κB signaling pathway activation and excessive inflammation. Frontiers in Immunology (2023).
2. Effects of E2 on the IDO1‐mediated metabolic KYN pathway in OVX female mice. Journal of Cellular and Molecular Medicine (2024).
3. Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. Journal of Neuroinflammation (2008).