Altered SYNJ2BP-mediated mitochondrial-ER contacts in motor neuron disease.

Synaptojanin 2 binding protein (SYNJ2BP) is an outer mitochondrial membrane protein with a cytosolic PDZ domain that functions as a cellular signaling hub. Few studies have evaluated its role in disease. Here we use induced pluripotent stem cell (iPSC)-derived motor neurons and post-mortem tissue from patients with two hereditary motor neuron diseases, spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis type 4 (ALS4), and show that SYNJ2BP expression is increased in diseased motor neurons. Similarly, we show that SYNJ2BP expression increases in iPSC-derived motor neurons undergoing stress. Using proteomic analysis, we found that elevated SYNJ2BP alters the cellular distribution of mitochondria and increases mitochondrial-ER membrane contact sites. Furthermore, decreasing SYNJ2BP levels improves mitochondrial oxidative function in the diseased motor neurons. Together, our observations offer new insight into the molecular pathology of motor neuron disease and the role of SYNJ2BP in mitochondrial dysfunction.

Effectiveness and feasibility of the workout on wheels internet intervention (WOWii) for individuals with spinal cord injury: a randomized controlled trial.

STUDY DESIGN: Randomized-controlled trial (RCT) with immediate intervention (IMM) and wait-list control (WLC) groups; WLC participants received the intervention during delivery to subsequent cohorts. OBJECTIVES: Investigate the effectiveness and feasibility of a virtually-delivered exercise intervention. SETTING: Home and community. METHODS: A total of 168 middle-aged (49.6 [12.3] years old) men (57%) and women (43%) who lived an average 15.5 (12.3) years with spinal cord injury (SCI) participated. The 16-week program provides users (a) website access with exercise information, resources, and 16 skill-building modules; (b) virtual 60-minute, group-based weekly meetings; and (c) a starter package of exercise equipment. Primary outcomes included subjective physical activity (IPAQ) and objective exercise (Polar A300 wrist-based activity monitor and H7 heart rate strap). Secondary outcomes included fitness indices during a maximal arm crank test, plus self-reported exercise barriers, exercise self-efficacy, and goal-directed thinking. RESULTS: RCT results indicate significant between group differences in participants' self-reported weekly time spent in vigorous-intensity PA and goal directed thinking but not for fitness changes. Data combined for IMM and WLC participants from Polar monitoring show participants performed 150 min per week of aerobic exercise plus reported significantly greater time spent in moderate-PA, vigorous-PA, self-efficacy for exercise and nutrition, goal directed thinking, and exercise barriers. Oxygen uptake (V̇O2 peak) and power output (watts max) were the only physiologic measures to demonstrate significant change, with a moderate effect size. CONCLUSION: This virtually-delivered program offers a promising approach to increase exercise among those with SCI and may help participants perceive fewer motivational barriers and greater self-efficacy.

Group Lifestyle Balance Adapted for Individuals With Impaired Mobility: Outcomes for 6-Month RCT and Combined Groups at 12 Months.

INTRODUCTION: This study examines the feasibility and effectiveness of an intensive lifestyle intervention adapted for people with impaired mobility. STUDY DESIGN: This was a randomized, wait-list controlled trial. The experimental group immediately received the 12-month weight loss program; the wait-list control group received it after a 6-month delay. Between-group comparisons were conducted for the 6-month RCT study design. Repeated measures were conducted for both groups combined after receiving the 12-month intervention. Data were collected August 2015-February 2017 and analyzed in 2017. SETTING/PARTICIPANTS: A community-based sample received 23, group-based sessions via a mix of telephone and in-person sessions in a hospital-based setting. Participants with impaired mobility (n=66) were middle-aged (49.80 [SD=11.37] years), mostly White (66.7%), female (66.7%), and most commonly had spinal cord injury (47.0%). INTERVENTION: The 12-month intervention delivered 23 group-based sessions that promoted weight loss through reducing caloric intake and increasing physical activity. MAIN OUTCOME MEASURES: Primary outcomes were effectiveness measured as change in weight and time spent in moderate physical activity. Feasibility was assessed in 12-month combined group analyses, measured as retention, attendance, and dietary self-monitoring. RESULTS: The 6-month RCT results showed that the immediate and delayed groups differed significantly (p<0.05) in weight (-1.66 [SD=4.42] kg loss vs 0.05 [SD=4.15] kg gain) and moderate physical activity (52.93 [SD=90.74] minutes/week increase vs -14.22 [SD=96.02] minutes/week decrease), accounting for baseline weight, time with disability, and age of onset. The 12-month results with groups combined demonstrated 74.2% retention and 77.7% core session attendance. Self-monitoring was higher in the delayed group (77.3%), who used a smartphone app, than the immediate group (47.3%), who mostly used paper trackers. Participants achieved significant 12-month weight loss of 3.31 (SD=10.13) kg (d=0.33) in mixed modeling analyses with groups combined yet did not significantly increase moderate physical activity. CONCLUSIONS: Group Lifestyle Balance Adapted for Individuals with Impaired Mobility is a feasible, effective approach to teach healthy lifestyle skills to individuals with mobility impairment, yielding modest weight loss and enhanced self-efficacy. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT03307187.

Pericyte transplantation improves skeletal muscle recovery following hindlimb immobilization.

Conditions of extended bed rest and limb immobilization can initiate rapid and significant loss of skeletal muscle mass and function. Physical rehabilitation is standard practice following a period of disuse, yet mobility may be severely compromised, and recovery is commonly delayed or incomplete in special populations. Thus, a novel approach toward recovery of muscle mass is highly desired. Pericytes [neuron-glial antigen 2 (NG2)+CD31-CD45- (Lineage- [Lin-]) and CD146+Lin-] demonstrate capacity to facilitate muscle repair, yet the ability to enhance myofiber growth following disuse is unknown. In the current study, 3-4-mo-old mice were unilaterally immobilized for 14 d (IM) or immobilized for 14 d followed by 14 d of remobilization (RE). Flow cytometry and targeted gene expression analyses were completed to assess pericyte quantity and function following IM and RE. In addition, a transplantation study was conducted to assess the impact of pericytes on recovery. Results from targeted analyses suggest minimal impact of disuse on pericyte gene expression, yet NG2+Lin- pericyte quantity is reduced following IM (P < 0.05). Remarkably, pericyte transplantation recovered losses in myofiber cross-sectional area and the capillary-to-fiber ratio following RE, whereas deficits remained with vehicle alone (P = 0.01). These findings provide the first evidence that pericytes effectively rehabilitate skeletal muscle mass following disuse atrophy.-Munroe, M., Dvoretskiy, S., Lopez, A., Leong, J., Dyle, M. C., Kong, H., Adams, C. M., Boppart, M. D. Pericyte transplantation improves skeletal muscle recovery following hindlimb immobilization.