The effect of citalopram treatment on amyloid-β precursor protein processing and oxidative stress in human hNSC-derived neurons

Selective Serotonin Reuptake Inhibitors (SSRIs) may hold therapeutic benefits for people with Alzheimer’s disease (AD). SSRIs may perturb AD progression, or the conversion from MCI to AD, via increased neurogenesis, reduced oxidative stress and/or favourable Amyloid-β Precursor Protein (AβPP) processing. This study used iPSC derived cortical neuronal cells carrying 3 different PSEN1 mutations, to investigate the effect of treatment with the SSRI, Citalopram on AβPP processing and oxidative stress. Control and PSEN1 mutation (L286V, A246E, M146L) iPSC-derived neurons were treated with Citalopram for 45 days. ADAM10 activity, AβPP processing and Aβ generation was measured in addition to cellular redox status. Citalopram treatment reduced the Aβ1-42:40 ratio in control but not in fAD PSEN1 cells. ADAM10 activity was increased with Citalopram treatments in fAD PSEN1 cell lines, which was also seen for sAβPPα secretion. Lower superoxide generation in fAD PSEN1 cells following Citalopram treatment was identified, although there was no effect on end markers of oxidative stress. Treatment with Citalopram appears to have little effect on Aβ generation in fADPSEN1 cells, but our findings suggest that treatment can significantly increase non-amyloidogenic AβPP processing and reduce oxidative stress. These changes may explain why SSRIs appear most effective in the prodromal period of the disease progression, as opposed to reducing established AD pathology. Further investigation of specific pathways conferring the beneficial effects of SSRIs treatment are warranted

Physical and physiological demands of elite rugby union officials

Elsworthy, N ORCiD: 0000-0002-5223-6803Purpose: To examine the movement and physiological demands of rugby union officiating in elite competition. Methods: Movement demands of 9 elite officials across 12 Super Rugby matches were calculated, using global positioning system devices. Total distance (in m), relative distance (in m·min-1), and percentage time spent in various speed zones were calculated across a match. Heart-rate (HR) responses were also recorded throughout each match. Cohen d effect sizes were reported to examine the within-match variations. Results: The total distance covered was 8030 (506) m, with a relative distance of 83 (5) m·min-1 and with no differences observed between halves. Most game time was spent at lower movement speeds (76% [2%]; 7.0 m·s-1 between halves (d = 2.85). Mean HR was 154 (10) beats·min-1 (83.8 [2.9]%HRmax), with no differences observed between the first and second halves. Most game time was spent between 81%HRmax and 90%HRmax (40.5% [7.5%]) with no observable differences between halves. Distances covered above 5.1 m·s-1 were highest during the first 10 min of a match, while distance at speeds 3.7 to 5 m·s-1 decreased during the final 10 min of play. Conclusions: These findings highlight the highly demanding and intermittent nature of rugby union officiating, with only some minor variations in physical and physiological demands across a match. These results have implications for the physical preparation of professional rugby union referees. © 2018 Human Kinetics, Inc