Assessing Human Spatial Navigation in a Virtual Space and its Sensitivity to Exercise.

Spatial navigation (SN) is the ability to locomote through the environment, which requires an understanding of where one is located in time and space. This capacity is known to rely on the sequential firing of place cells within the hippocampus. SN is an important behavior to investigate as this process deteriorates with age, especially in neurodegenerative disorders. However, the investigation of SN is limited by the lack of sophisticated behavioral techniques to assess this hippocampal-dependent task. Therefore, the goal of this protocol was to develop a novel, real-world approach to studying SN in humans. Specifically, an active virtual SN task was developed using a cross-platform game engine. During the encoding phase, participants navigated their way through a virtual city to locate landmarks. During the remembering phase, participants remembered where these reward locations were and delivered items to these locations. Time to find each location was captured and episodic memory was assessed by a free recall phase, including aspects of place, order, item, and association. Movement behavior (x, y, and z coordinates) was assessed through an asset available in the game engine. Importantly, results from this task demonstrate that it accurately captures both spatial learning and memory abilities as well as episodic memory. Further, findings indicate that this task is sensitive to exercise, which improves hippocampal functioning. Overall, the findings suggest a novel way to track human hippocampal functioning over the course of time, with this behavior being sensitive to physical activity training paradigms.

Dispositional mindfulness and its relationship to exercise motivation and experience.

Mindfulness is the psychological state of staying attuned to the present moment, without ruminating on past or future events, and allowing thoughts, feelings, or sensations to arise without judgment or attachment. Previous work has shown that heightened dispositional mindfulness is associated with the awareness of the importance of exercise, exercise self-efficacy, exercise motivation, and self-reported exercise level. However, more methodologically rigorous studies are needed to understand the relationship between mindfulness and the psychological mechanisms related to exercise motivation, including the identification of why individuals are motivated to engage in exercise, the subjective experience of exercise, and the propensity for exercise dependence and addiction. In this cross-sectional investigation, we utilized the framework of the Self-Determination Theory to examine the hypothesis that heightened dispositional mindfulness (as measured by the Mindful Attention Awareness Scale) would be associated with increased levels of exercise motivation that were derived by higher levels of autonomous self-regulation. Individuals were recruited from urban areas who self-reported either low (exercising 2 or fewer times per week for 20 min or less; n = 78) or moderate (exercising 1 or 2 times per week for 20 min or more; n = 127) levels of exercise engagement. As hypothesized, heightened dispositional mindfulness was significantly associated with heightened levels of exercise self-determination as measured by the Behavioral Regulations in Exercise Questionnaire, with this effect being driven by negative associations with amotivation, external regulation, and introjected regulation. Additionally, we found that heightened dispositional mindfulness was associated with lower levels of psychological distress upon exercise and decreased exercise dependence/addiction. Overall, increased dispositional mindfulness may support a healthy relationship with exercise. These findings have implications for the utility of mindfulness interventions to support the regulation of exercise behaviors in service of enhancing exercise motivation and engagement.

Inhibition of Neutrophil Extracellular Trap Formation after Stem Cell Transplant by Prostaglandin E2.

RATIONALE: Autologous and allogeneic hematopoietic stem cell transplant (HSCT) patients are susceptible to pulmonary infections, including bacterial pathogens, even after hematopoietic reconstitution. We previously reported that murine bone marrow transplant (BMT) neutrophils overexpress cyclooxygenase-2, overproduce prostaglandin E2 (PGE2), and exhibit defective intracellular bacterial killing. Neutrophil extracellular traps (NETs) are DNA structures that capture and kill extracellular bacteria and other pathogens. OBJECTIVES: To determine whether NETosis was defective after transplant and if so, whether this was regulated by PGE2 signaling. METHODS: Neutrophils isolated from mice and humans (both control and HSCT subjects) were analyzed for NETosis in response to various stimuli in the presence or absence of PGE2 signaling modifiers. MEASUREMENTS AND MAIN RESULTS: NETs were visualized by immunofluorescence or quantified by Sytox Green fluorescence. Treatment of BMT or HSCT neutrophils with phorbol 12-myristate 13-acetate or rapamycin resulted in reduced NET formation relative to control cells. NET formation after BMT was rescued both in vitro and in vivo with cyclooxygenase inhibitors. Additionally, the EP2 receptor antagonist (PF-04418948) or the EP4 antagonist (AE3-208) restored NET formation in neutrophils isolated from BMT mice or HSCT patients. Exogenous PGE2 treatment limited NETosis of neutrophils collected from normal human volunteers and naive mice in an exchange protein activated by cAMP- and protein kinase A-dependent manner. CONCLUSIONS: Our results suggest blockade of the PGE2-EP2 or EP4 signaling pathway restores NETosis after transplantation. Furthermore, these data provide the first description of a physiologic inhibitor of NETosis.