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Engels, G.

Publications and source records attributed to Engels, G..

2 recordsLinked to original sources

Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson’s disease

Reduced levels of dopamine in Parkinsons disease (PD) contribute to changes in learning, resulting from the loss of midbrain dopamine neurons that transmit a teaching signal to the striatum. Dopamine medication used by PD patients has previously been linked to either behavioral changes during learning itself or adjustments in approach and avoidance behavior after learning. To date, however, very little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. We assessed 24 PD patients on and off dopaminergic medication and 24 healthy controls (HC) performing a probabilistic reinforcement learning task, while undergoing functional magnetic resonance imaging. During learning, medication in PD reduced an overemphasis on negative outcomes. When patients were on medication, learning rates were lower for negative (but not positive) outcomes and concurrent striatal BOLD responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by striatal BOLD response alterations. These findings highlight dopamine-driven learning differences in PD and provide new insight into how changes in learning impact the transfer of learned value to approach/avoidance responses in novel contexts.

neuroscience

Charcot-Leyden Crystals activate the NLRP3 inflammasome and cause IL-1β inflammation

Charcot-Leyden crystals (CLCs) are Galectin-10 protein crystals that can form after eosinophils degranule. CLCs can appear and persist in tissues from patients with eosinophilic disorders, such as asthma, allergic reactions, fungal, and helminthic infections. Despite abundant reports of their occurrence in human disease, the inflammatory potential of CLCs has remained unknown. Here we show that CLCs induce IL-1{beta} release upon their uptake by primary human macrophages in vitro, and that they induce inflammation in vivo in mouse models of acute peritonitis and bronchitis. CLC-induced IL-1{beta} was dependent on NLRP3 and caspase-1, and their instillation in inflammasome reporter mice promoted the assembly of ASC complexes and IL-1{beta} secretion in the lungs. Our findings reveal that CLCs are recognized by the NLRP3 inflammasome, which may sustain inflammation that follows eosinophilic inflammatory processes.

immunology