Neuroinﬂammatory alterations in trait anxiety: modulatory effects of minocycline

Translational Psychiatry, 2020 · DOI: https://doi.org/10.1038/s41398-020-00942-y · Published: July 15, 2020

Simple Explanation

High trait anxiety is a risk factor for anxiety and depression. This study investigates neuroinflammation in mice with high trait anxiety (HAB) compared to normal anxiety mice (NAB). The researchers found microglial alterations in the hippocampus of HAB mice. Specifically, there was an increased density of microglia in the dentate gyrus (DG). Treatment with minocycline, an anti-inflammatory drug, reduced anxiety-related behavior in HAB mice. This reduction was associated with decreased microglial activity in the DG.

Study Duration

28 d (systemic minocycline), 5 or 11 d (local minocycline)

Participants

Male HAB and NAB mice (11-22w)

Evidence Level

Not specified

Key Findings

1
HAB mice exhibited enhanced density and average cell area of Iba1+ microglia in the dentate gyrus (DG) of the hippocampus compared to NAB controls.
2
Chronic oral minocycline reduced HAB hyperanxiety, which was associated with significant decreases in Iba1+ and CD68+Iba1+ cell densities in the DG.
3
Longer periods (10 days) of minocycline microinfusions locally into the DG of HAB reduced Iba-1+ cell density and attenuated hyperanxiety-related behavior.

Research Summary

The study investigated neuroinflammatory alterations in high trait anxiety using a mouse model (HAB). Results showed increased microglial density and activity in the hippocampus of HAB mice, particularly in the dentate gyrus (DG). Minocycline treatment, both systemic and local, reduced microglial activity in the DG and attenuated hyperanxiety-related behavior in HAB mice.

Practical Implications

Therapeutic potential

Drugs with microglia-targeted anti-inflammatory properties could be a novel therapeutic approach for individuals genetically predisposed to hyperanxiety.

Understanding Pathophysiology

Central inflammatory disturbances are evident in individuals with high trait anxiety, even without known triggers of inflammation.

Targeted Interventions

Modulating microglia activity locally in the DG can attenuate hyperanxiety, suggesting a specific target for intervention.

Study Limitations

1
The study was conducted on a mouse model, and results may not directly translate to humans.
2
The exact mechanisms by which minocycline modulates microglial activity and reduces anxiety are not fully understood.
3
The study focused on specific brain regions, and neuroinflammatory alterations in other areas may also contribute to trait anxiety.

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