Neuroinflammatory alterations in trait anxiety: modulatory effects of minocycline
| Autor: | Michael S. Unger, Nicolas Singewald, Maria Kharitonova, Christoph Schwarzer, Susanne A. Wolf, Helmut Kettenmann, Sinead Rooney, Simone B. Sartori, Ludwig Aigner, Anupam Sah |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Hippocampus Minocycline Anxiety Anxiolytic Article lcsh:RC321-571 Mice Cellular and Molecular Neuroscience Internal medicine medicine Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Neuroinflammation Microglia business.industry CD68 Dentate gyrus Anxiety Disorders Psychiatry and Mental health medicine.anatomical_structure Endocrinology Anti-Anxiety Agents medicine.symptom Function and Dysfunction of the Nervous System Psychiatric disorders business Neuroscience medicine.drug |
| Zdroj: | Translational Psychiatry, Vol 10, Iss 1, Pp 1-10 (2020) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | High trait anxiety is a substantial risk factor for developing anxiety disorders and depression. While neuroinflammation has been identified to contribute to stress-induced anxiety, little is known about potential dysregulation in the neuroinflammatory system of genetically determined pathological anxiety or high trait anxiety individuals. We report microglial alterations in various brain regions in a mouse model of high trait anxiety (HAB). In particular, the dentate gyrus (DG) of the hippocampus of HABs exhibited enhanced density and average cell area of Iba1+, and density of phagocytic (CD68+/Iba1+) microglia compared to normal anxiety (NAB) controls. Minocycline was used to assess the capacity of a putative microglia ‘inhibitor’ in modulating hyperanxiety behavior of HABs. Chronic oral minocycline indeed reduced HAB hyperanxiety, which was associated with significant decreases in Iba1+ and CD68+Iba1+ cell densities in the DG. Addressing causality, it was demonstrated that longer (10 days), but not shorter (5 days), periods of minocycline microinfusions locally into the DG of HAB reduced Iba-1+ cell density and attenuated hyperanxiety-related behavior, indicating that neuroinflammation in the DG is at least partially involved in the maintenance of pathological anxiety. The present data reveal evidence of disturbances in the microglial system of individuals with high trait anxiety. Minocycline attenuated HAB hyperanxiety, likely by modulation of microglial activity within the DG. Thus, the present data suggest that drugs with microglia-targeted anti-inflammatory properties could be promising as novel alternative or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals genetically predisposed to hyperanxiety. |
| Databáze: | OpenAIRE |
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