Acute calorie restriction modifies cognition and anxiety-like behavior in mice by regulating IL-1β priming and activation within the brain

Abstract

IL-1 β is a central regulator of many biobehaviors including cognition and anxiety, however, how dietary interventions, such as acute calorie restriction (ACR), can regulate IL-1 β remains unknown. Here, we show that ACR, as a 24 hour fast, can regulate the priming and activation of IL-1beta in the brain. To address if ACR can influence IL-1 β priming qRT-PCR was used to analyze gene expression. All regions, except the hippocampus, showed a reduction in IL-1 β mRNA due to ACR. Despite changes in mRNA, no changes were found in IL-1 β protein. Since IL-1 β requires activation via caspase-1, we analyzed caspase-1 activity, and found it was reduced throughout the brain. To determine if alterations in inflammatory signaling alter neurotransmitter levels we examined dopamine (DA), 3,4-Dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-Hydroxyindoleacetic acid (5-HIAA) via HPLC. HVA was increased in the amygdala and hippocampus, while DA and 5-HT were increased in the hypothalamus following ACR. To determine if these changes modify behavior, mice were tested on the elevated zero maze (EZM), novel object (NOR), and novel position recognition (NPR) tasks. Mice exhibited reduced anxiety-like behavior as well as improved novel object/position discrimination in the NOR and NPR tests due to ACR. Taken together, these data show that ACR can decrease the priming and activation of IL-1 β , and that this decrease may manifest as changes in behavioral testing.