Piezo channels contribute to the regulation of myelination in Schwann cells.

Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the limbs and mechanical compressions from daily activities. In Schwann cells, signaling molecules sensitive to stiffness or stretch of the extracellular matrix, such as YAP/TAZ, have been shown to be critical for Schwann cell development and peripheral nerve regeneration. YAP/TAZ have also been suggested to contribute to tumorigenesis, neuropathic pain, and inherited disorders. Yet, the role of mechanosensitive ion channels in myelinating Schwann cells is vastly unexplored. Here we comprehensively assessed the expression of mechanosensitive ion channels in Schwann cells and identified that PIEZO1 and PIEZO2 are among the most abundant mechanosensitive ion channels expressed by Schwann cells. Using classic genetic ablation studies, we show that PIEZO1 is a transient inhibitor of radial and longitudinal myelination in Schwann cells. Contrastingly, we show that PIEZO2 may be required for myelin formation, as the absence of PIEZO2 in Schwann cells delays myelin formation. We found an epistatic relationship between PIEZO1 and PIEZO2, at both the morphological and molecular levels. Finally, we show that PIEZO1 channels affect the regulation of YAP/TAZ activation in Schwann cells. Overall, we present here the first demonstration that PIEZO1 and PIEZO2 contribute to mechanosensation in Schwann cells as well myelin development in the peripheral nervous system.

YAP and TAZ regulate Schwann cell proliferation and differentiation during peripheral nerve regeneration.

YAP and TAZ are effectors of the Hippo pathway that controls multicellular development by integrating chemical and mechanical signals. Peripheral nervous system development depends on the Hippo pathway. We previously showed that loss of YAP and TAZ impairs the development of peripheral nerve as well as Schwann cell myelination. The role of the Hippo pathway in peripheral nerve regeneration has just started to be explored. After injury, Schwann cells adopt new identities to promote regeneration by converting to a repair-promoting phenotype. While the reprogramming of Schwann cells to repair cells has been well characterized, the maintenance of such repair phenotype cannot be sustained for a very long period, which limits nerve repair in human. First, we show that short or long-term myelin maintenance is not affected by defect in YAP and TAZ expression. Using crush nerve injury and conditional mutagenesis in mice, we also show that YAP and TAZ are regulators of repair Schwann cell proliferation and differentiation. We found that YAP and TAZ are required in repair Schwann cells for their redifferentiation into myelinating Schwann cell following crush injury. In this present study, we describe how the Hippo pathway and YAP and TAZ regulate remyelination over time during peripheral nerve regeneration.

Examining sex differences in the association between sedentary behavior and cognitive function in bariatric surgery patients.

BACKGROUND: Obesity is associated with cognitive impairment. A potential contributor to these deficits is sedentary behavior (SB), which is linked to poorer cognitive functioning in other populations. Little is known about the association between SB and cognitive function in bariatric surgery populations. OBJECTIVES: This cross-sectional study examined the association between SB and cognitive function in preoperative bariatric surgery patients, as well as possible sex differences in this relationship. SETTING: Data were collected at 2 health centers in the United States. METHODS: A total of 121 participants (43.2 ± 10.3 yr of age) scheduled for Roux-en-Y gastric bypass or sleeve gastrectomy completed the National Institute of Health (NIH) Toolbox for the Assessment of Neurological and Behavioral Function Cognition Domain, a computerized neuropsychological assessment battery. Participants wore a waist-mounted accelerometer for 7 consecutive days to measure SB and light-intensity physical activity (LPA). RESULTS: Pearson and partial correlations found no significant relationships between cognitive function and SB or LPA in the full sample. However, partial correlations controlling for LPA found that greater SB was associated with poorer performance on List Sorting Working Memory Test in women (r = -.28; P = .006), whereas there was a positive relationship between SB and Dimensional Change Card Sort for men (r = .51; P = .015; 95% CI [.25, .73]). CONCLUSIONS: These results showed that greater SB, independent of LPA, is associated with poorer working memory in women and better set shifting ability in men. Future studies should examine the possibility of domain-specific cognitive effects associated with SB in bariatric surgery samples and clarify possible sex differences.

The gut microbiome, mild cognitive impairment, and probiotics: A randomized clinical trial in middle-aged and older adults.

BACKGROUND: Advancing age coincides with changes in the gut microbiome and a decline in cognitive ability. Psychobiotics are microbiota-targeted interventions that can result in mental health benefits and protect the aging brain. This study investigated the gut microbiome composition and predicted microbial functional pathways of middle-aged and older adults that met criteria for mild cognitive impairment (MCI), compared to neurologically healthy individuals, and investigated the impact of probiotic Lactobacillus rhamnosus GG (LGG) in a double-blind, placebo-controlled, randomized clinical trial. A total of 169 community-dwelling middle-aged (52-59 years) and older adults (60-75 years) received a three-month intervention and were randomized to probiotic and placebo groups. Participants were further subdivided based on cognitive status into groups with intact or impaired cognition and samples were collected at baseline and post supplementation. RESULTS: Microbiome analysis identified Prevotella ruminicola, Bacteroides thetaiotaomicron, and Bacteroides xylanisolvens as taxa correlated with MCI. Differential abundance analysis at baseline identified Prevotella as significantly more prevalent in MCI subjects compared to cognitively intact subjects (ALDEx2 P = 0.0017, ANCOM-BC P = 0.0004). A decrease in the relative abundance of the genus Prevotella and Dehalobacterium in response to LGG supplementation in the MCI group was correlated with an improved cognitive score. CONCLUSIONS: Our study points to specific members of the gut microbiota correlated with cognitive performance in middle-aged and older adults. Should findings be replicated, these taxa could be used as key early indicators of MCI and manipulated by probiotics, prebiotics, and symbiotics to promote successful cognitive aging. Registered under ClinicalTrials.gov Identifier no. NCT03080818.