No abstract

The neuropeptide oxytocin plays a role in social cognition and affective processing. The neural processes underlying these effects are not well understood. Modulation of connectivity strength between subcortical and cortical regions has been suggested as one possible mechanism. The current study investigated effects of intranasal oxytocin administration on resting-state functional connectivity between amygdala and medial prefrontal cortex (mPFC), as two central regions involved in social-cognitive and affective processing. Going beyond previous work that largely examined young male participants, our study comprised young and older men and women to identify age and sex variations in oxytocin's central processes. This approach was based on known hormonal differences among these groups and emerging evidence of sex differences in oxytocin's effects on amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective processing. In a double-blind design, 79 participants were randomly assigned to self-administer either intranasal oxytocin or placebo before undergoing resting-state functional magnetic resonance imaging. Using a targeted region-to-region approach, resting-state functional connectivity strength between bilateral amygdala and mPFC was examined. Participants in the oxytocin compared to the placebo group and men compared to women had overall greater amygdala mPFC connectivity strength at rest. These main effects were qualified by a significant three-way interaction: while oxytocin compared to placebo administration increased resting-state amygdala mPFC connectivity for young women, oxytocin did not significantly modulate connectivity in the other age-by-sex subgroups. This study provides novel evidence of age-by-sex differences in how oxytocin modulates resting-state brain connectivity, furthering our understanding of how oxytocin affects brain networks at rest.

The association between systemic inflammation and cognitive deficits is well-documented. Further, previous studies have shown that systemic inflammation levels increase with age. The present study took a novel approach by examining the extent to which systemic inflammation levels mediated age-related cognitive decline. Forty-seven young and 46 older generally healthy adults completed two cognitive tasks measuring processing speed and short-term memory, respectively. Serum concentrations of three inflammatory biomarkers (including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP)) were measured in each participant. Both cognitive measures showed age-related deficits. In addition, levels of IL-6 and TNF-α were elevated with age. IL-6 partially mediated the difference in processing speed between the young and the older participant age group; there was no mediation effect for TNF-α and CRP. Considering chronological age, IL-6 partially accounted for age-related impairment in processing speed within older but not young participants. No effects were found for short-term memory. Evidence from this research supports the role of inflammatory processes in age-related cognitive decline. Processes involved in this mediation and differences in inflammatory influence on specific cognitive functions are discussed.

miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment.

Short-term memory, verbal fluency, and positive affect in middle-old age may contribute to resilience against online spear-phishing attacks. These results inform mechanisms of online fraud susceptibility and real-life decision-supportive interventions towards fraud risk reduction in aging.