title: Central metabolite changes and activation of microglia after peripheral interleukin-2 challenge.
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.
authors: Central Institute of Mental Health, Institute of Psychopharmacology, 68159 Mannheim, Germany.
authors: Peggy
authors: P
authors: Schneider
authors: Wolfgang
authors: W
authors: Weber-Fahr
authors: Nina
authors: N
authors: Schweinfurth
authors: Ying-Jui
authors: YJ
authors: Ho
authors: Alexander
authors: A
authors: Sartorius
authors: Rainer
authors: R
authors: Spanagel
authors: Cornelius R
authors: CR
authors: Pawlak
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005434:Flow Cytometry; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D007294:Inositol / Q000032:analysis; D007376:Interleukin-2 / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D059906:Neuroimaging; D017397:Prefrontal Cortex / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D007376:Interleukin-2; D007294:Inositol; D005680:gamma-Aminobutyric Acid