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Abstract Cholesterol is a vital component of the cell membrane and plays an essential role in mediating integral membrane protein function. Altered cholesterol regulation has been implicated in neurological diseases that are associated with blood–brain barrier breakdown. However, the role of brain barrier function in inherited disorders of cholesterol metabolism, such as Niemann-Pick disease C1 (NP-C1), remains unclear. In this study, we determined how cholesterol depletion with U18666A, a chemical inhibitor of NPC1 protein, as well as with the cholesterol-depleting agent methyl-β cyclodextrin (MβCD), impacted brain endothelial cell barrier function. We hypothesized that cholesterol depletion would decrease barrier integrity by disrupting tight junction protein continuity. To test this hypothesis, we differentiated human-induced pluripotent stem cells into brain microvascular endothelial cells (hiBMECs). We then assessed barrier integrity by quantifying trans-endothelial electrical resistance (TEER), small fluorescent molecule permeability, and tight junction continuity and protein levels. We now show that U18666A-treated hiBMECs demonstrated a 75% decrease in TEER and 9-fold increase in sodium fluorescein permeability. Similar trends were observed for hiBMECs treated with MβCD, which showed significantly lowered TEER (93% decrease) and increased sodium fluorescein permeability (20-fold higher). We also observed decreased continuity of the tight junction proteins occludin (13% lower) and claudin-5 (8% lower) as well as a 53% decrease in claudin-5 protein with U18666A treatment. Co-treating U18666A-treated hiBMECs with hydroxypropyl-β cyclodextrin (HPβCD), which releases lysosomal cholesterol, prevented these changes. Together, our results demonstrate that cholesterol is vital for hiBMEC barrier function and tight junction continuity. This study highlights the potential of therapeutics targeted to brain endothelium in NP-C1 and other cholesterol metabolism disorders. 

Math anxiety (MA) and math performance are generally negatively correlated (Barroso et al., 2020; Namkung et al., 2019). However, the mechanisms underlying this negative association remain unclear. According to the Attentional Control Theory (ACT; Eysenck, et al., 2007), anxious individuals experience impaired attentional control during problem solving, which compromises their performance on cognitive tasks. In a sample of 168 elementary and middle school students, the current study used an eye-tracking approach to investigate whether math-anxious students exhibit deficits in their attentional control during a math problem solving task, and whether such attentional control deficits account for the negative association between MA and performance on this math task. Consistent with the ACT, we found that students with higher MA were more likely to engage attention to both task-relevant and task-irrelevant distractors during problem solving, and their enhanced attention to these distractors was associated with their impaired performance on the math task. These findings suggest that the MA-related math performance deficit is partly mediated by impaired attentional control, which is indicated by the maladaptive attentional bias toward distracting information during math problem solving. 

This article synthesizes findings from an international virtual conference, funded by the United States National Science Foundation, focused on the home mathematics environment (HME). In light of inconsistencies and gaps in research investigating relations between the HME and children’s outcomes, the purpose of the conference was to discuss actionable steps and considerations for future work. The conference was composed of international researchers with a wide range of expertise and backgrounds. Presentations and discussions during the conference centered broadly on the need to better operationalize and measure the HME as a construct—focusing on issues related to child, family, and community factors, country and cultural factors, and the cognitive and affective characteristics of caregivers and children. Results of the conference and a subsequent writing workshop include a synthesis of core questions and key considerations for the field of research on the HME. Findings highlight the need for the field at large to use multi-method measurement approaches to capture nuances in the HME, and to do so with increased international and interdisciplinary collaboration, open science practices, and communication among scholars.