ß-arrestin1 regulates astrocytic reactivity via Drp1-dependent mitochondrial fission: implications in postoperative delirium.

Postoperative delirium (POD) is a frequent and debilitating complication, especially amongst high risk procedures, such as orthopedic surgery. This kind of neurocognitive disorder negatively affects cognitive domains, such as memory, awareness, attention, and concentration after surgery; however, its pathophysiology remains unknown. Multiple lines of evidence supporting the occurrence of inflammatory events have come forward from studies in human patients' brain and bio-fluids (CSF and serum), as well as in animal models for POD. ß-arrestins are downstream molecules of guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). As versatile proteins, they regulate numerous pathophysiological processes of inflammatory diseases by scaffolding with inflammation-linked partners. Here we report that ß-arrestin1, one type of ß-arrestins, decreases significantly in the reactive astrocytes of a mouse model for POD. Using ß-arrestin1 knockout (KO) mice, we find aggravating effect of ß-arrestin1 deficiency on the cognitive dysfunctions and inflammatory phenotype of astrocytes in POD model mice. We conduct the in vitro experiments to investigate the regulatory roles of ß-arrestin1 and demonstrate that ß-arrestin1 in astrocytes interacts with the dynamin-related protein 1 (Drp1) to regulate mitochondrial fusion/fission process. ß-arrestin1 deletion cancels the combination of ß-arrestin1 and cellular Drp1, thus promoting the translocation of Drp1 to mitochondrial membrane to provoke the mitochondrial fragments and the subsequent mitochondrial malfunctions. Using ß-arrestin1-biased agonist, cognitive dysfunctions of POD mice and pathogenic activation of astrocytes in the POD-linked brain region are reduced. We, therefore, conclude that ß-arrestin1 is a promising target for the understanding of POD pathology and development of POD therapeutics.

Honesty-humility and prosocial behavior: The mediating roles of perspective taking and guilt-proneness.

The prosocial personality trait of honesty-humility has received extensive attention in the last decade. However, research on the mechanism underlying the relationship between honesty-humility and prosocial behavior is rather scarce. This study aims to explore the internal mechanism underlying this relationship to draw a complete picture of the honesty-humility trait. A sample of 458 Chinese young adults was obtained to complete self-report measures of honesty-humility, perspective taking, guilt-proneness, and prosocial behavior. The mediation model revealed that: (1) honesty-humility positively related to prosocial behavior; (2) perspective taking and guilt-proneness mediated the relationship between honesty-humility and prosocial behavior, separately; and (3) the effect of honesty-humility on prosocial behavior was mediated via perspective taking and then guilt-proneness. In conclusion, we provide an initial support for the mediating roles of perspective taking and guilt-proneness in the relationship between honesty-humility and prosocial behavior. Both theoretical and practical implications for understanding the psychological mechanisms of prosocial behavior are discussed.