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Published on: July 25, 2022
Central metabolite changes and activation of microglia after peripheral interleukin-2 challenge
Peggy Schneider1, Wolfgang Weber-Fahr, Nina Schweinfurth
1Central Institute of Mental Health, Institute of Psychopharmacology, 68159 Mannheim, Germany.
Insights
Interleukin-2 (IL-2) affects the brain, potentially influencing psychiatric disorders. This study shows IL-2 alters brain metabolites and increases microglia activity, suggesting microglia mediate IL-2’s immune-CNS communication.
Area of Science:
- Neuroimmunology
- Psychiatry
- Neuroscience
Background:
- Interleukin-2 (IL-2) regulates T-cells and impacts the central nervous system (CNS), with potential links to psychiatric disorders.
- The precise mechanism of IL-2's immune-CNS communication is unclear, though microglia are implicated as both source and target.
Purpose of the Study:
- To investigate changes in brain metabolites after peripheral IL-2 administration.
- To examine the role of microglia in mediating IL-2's central nervous system effects.
- To correlate IL-2-induced brain metabolite changes with anxiety-like behaviors.
Main Methods:
- Magnetic Resonance Spectroscopy (MRS) was used to measure brain metabolites in rat prefrontal cortex (PFC) and hippocampus.
- Behavioral tests (elevated plus-maze) assessed anxiety-like measures post-IL-2 injection.
- Fluorescence-activated cell sorting (FACS) quantified CD25(+) microglia populations.
Main Results:
- Peripheral IL-2 injection significantly increased myo-inositol levels in the PFC and hippocampus.
- A correlation was found between anxiety-like behaviors and hippocampal myo-inositol, a marker of microglia activity.
- FACS analysis revealed a significant increase in CD25(+) microglia in the hippocampus following IL-2 administration.
Conclusions:
- Microglia are implicated as mediators in the immune-CNS communication pathway involving IL-2.
- Peripheral IL-2 administration induces changes in brain metabolites and microglia activation, potentially contributing to neurobehavioral effects.
Abstract:
Interleukin (IL)-2 regulates the immune response through the proliferation of activated T-cells and also exerts effects on the central nervous system (CNS). Alongside having marked neurobehavioral effects, IL-2 has been suggested to impact on various psychiatric disorders. The immune-CNS communication of IL-2 remains unclear, although, it is suggested that microglia are the source and target of IL-2. Here, we analyzed changes in brain metabolites following a peripheral IL-2 challenge and examined the contribution of microglia in mediating these effects. Rats were assessed by magnetic resonance spectroscopy (MRS) in a 9.4 T scanner for baseline metabolite levels in the prefrontal cortex (PFC) and the hippocampus. After 7 days animals were scanned again following a single injection of IL-2 (2.5 μg/kg) and then tested on the elevated plus-maze for the correlation of IL-2-induced brain metabolites and measures of anxiety. In another experiment CD25(+) microglia cells were determined. A separate group of rats was injected either with IL-2 or vehicle, and afterward the PFC and hippocampus were dissected and fluorescence activated cell sorting (FACS) analysis was performed. The MRS scans in the intra-individual study design showed a significant increase in myo-inositol in the analyzed regions. A significant correlation of anxiety-like measures and myo-inositol, a marker for microglia activity, was found in the hippocampus. The FACS analysis showed a significant increase in CD25(+) microglia in the hippocampus compared to controls. The results support the role of microglia as a mediator in the immune-CNS communication and the effects of peripheral IL-2.
