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

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-1?. The bioavailability and activity of IL-1? 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-1? 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%, respectively. IL-1? protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed.Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain.

SUBMITTER: Towers AE

PROVIDER: S-EPMC5439304 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Towers Albert E AE Oelschlager Maci L ML Patel Jay J Gainey Stephen J SJ McCusker Robert H RH Freund Gregory G GG

Metabolism: clinical and experimental 20170309

<h4>Background</h4>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.<h4>Methods</h4>Male C57BL/6j, C57BL/6 ...[more]

PMID: 28521881

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Project description:Forest disturbance regimes are intensifying in many parts of the globe. In order to mitigate disturbance impacts a number of management responses have been proposed, yet their effectiveness in addressing changing disturbance regimes remains largely unknown. The strong positive relationship between forest age and the vulnerability to disturbances such as windthrows and bark beetle infestations suggests that a reduced rotation length can be a potent means for mitigating the impacts of natural disturbances. However, disturbance mitigation measures such as shortened rotation lengths (SRL) can also have undesired consequences on ecosystem services and biodiversity, which need to be considered in their application. Here, we used the process-based landscape and disturbance model iLand to investigate the effects of SRL on the vulnerability of a 16,000 ha forest landscape in Central Europe to wind and bark beetle disturbances. We experimentally reduced the current rotation length (between 100 and 115 years) by up to −40% in 10% increments, and studied effects on disturbance dynamics under current and future climate conditions over a 200-year simulation period. Simultaneously, we quantified the collateral effects of SRL on forest carbon stocks and indicators of biodiversity. Shortening the rotation length by 40% decreased disturbances by 14%. This effect was strongly diminished under future climate change, reducing the mitigating effect of shortened rotation to < 6%. Collateral effects were severe in the initial decades after implementation: Reducing the rotation length by 40% caused a spike in harvested timber volume (+ 92%), decreased total forest carbon storage by 6% and reduced the number of large trees on the landscape by 20%. The long-term effects of SRL were less pronounced. At the same time, SRL caused an increase in tree species diversity. Shortening rotation length can reduce the impact of wind and bark beetle disturbances, but the overall efficiency of the measure is limited and decreases under climate change. Given the potential for undesired collateral effects we conclude that a reduction of the rotation length is no panacea for managing increasing disturbances, and should be applied in combination with other management measures reducing risks and fostering resilience.

Dataset Information

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

Publications

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

Similar Datasets

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