Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition

Metabolism: Clinical and Experimental
Albert E TowersGregory G Freund

Abstract

Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, re...Continue Reading

Citations

Mar 10, 2019·Translational Psychiatry·Changhong LiYunlei Yang
Feb 8, 2021·Behavioural Brain Research·Randhall B CarteriLuis Valmor Portela
May 21, 2019·Brain, Behavior, and Immunity·Albert E TowersGregory G Freund
Nov 2, 2019·Current Opinion in Behavioral Sciences·Albert E Towers, Gregory G Freund

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