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Lu, O.

Publications and source records attributed to Lu, O..

2 recordsLinked to original sources

Effects of Exercise Frequency on Aortic Calcification in Hyperlipidemic Mice

Cardiovascular disease risk is associated with coronary artery calcification and is mitigated by regular exercise. However, the optimal regimen (activity level and frequency) for benefitting cardiovascular health is not clear. The surface area of calcium deposits, in addition to the quantity of calcium mineral, is a key factor in the risk of plaque rupture in humans due to compliance mismatch of edges with surrounding distensible tissue resulting in debonding. We previously found that aortic PET tracer uptake, a marker of mineral surface area, was reduced in hyperlipidemic (Apoe-/-) mice that underwent treadmill exercise, especially those in the low-speed (12.5 meters/min) regimen. To test the optimal exercise frequency on cardiovascular health, hyperlipidemic mice with baseline aortic calcification were subjected to none, 3- or 5-day/week treadmill regimen (12.5 meters/min for 30 min/day) for 5 weeks. MicroPET/microCT imaging and echocardiography were performed before and after the 5-week study. Results show that aortic calcification significantly progressed in all 3 groups, and 18F-NaF uptake increased in the control and 3-day groups, but not in the 5-day group. As for cardiac function, left ventricular (LV) systolic function was not affected but LV mass and wall thickness decreased in the 5-day group, suggesting cardiac remodeling. Skeletal bone density assessed at lumbar vertebrae shows that bone density decreased in all 3 groups. These findings suggest that, in mice with underlying calcific atherosclerosis, low-speed exercise and a frequency of 5 days/week is optimal for benefitting cardiovascular health.

physiology↗

Role of type I interferon signaling and microglia in the abnormal long term potentiation and object place recognition deficits of male mice with a mutation of the Tuberous Sclerosis 2 gene

Tuberous Sclerosis Complex (TSC) is a genetic disorder associated with high rates of intellectual disability and autism. Although previous studies focused on the role of neuronal deficits in the memory phenotypes of rodent models of TSC, the results presented here demonstrate a role for microglia in these deficits. Mice with a heterozygous null mutation of the Tsc2 gene (Tsc2+/-), show deficits in hippocampal dependent tasks, as well as abnormal long-term potentiation (LTP) in the hippocampal CA1 region. Here, we show that microglia and type I interferon signaling (IFN1) have a key role in the object place recognition (OPR; a hippocampal dependent task) deficits and abnormal LTP of Tsc2+/- male mice. Unexpectedly, we demonstrate that male, but not female, Tsc2+/- mice showed OPR deficits. Importantly, these deficits can be rescued by depletion of microglia, as well as by a genetic manipulation of a signaling pathway known to modulate microglia function (interferon-alpha/beta receptor alpha chain null mutation). In addition to rescuing the OPR deficits, depletion of microglia also reversed the abnormal LTP of the Tsc2+/- mice. Altogether, our results suggest that altered IFN1 signaling in microglia cause the abnormal LTP and OPR deficits of male Tsc2+/- mice.

neuroscience↗