This study characterizes the mechanisms underlying defects in synaptic transmission when DRP1 is ... more This study characterizes the mechanisms underlying defects in synaptic transmission when DRP1 is genetically eliminated. Viral-mediated knockout of DRP1 from the presynaptic terminal at the mouse calyx of Held increased initial release probability, reduced the size of synaptic vesicle recycling pool, and impaired synaptic vesicle recycling. Transmission defects could be partially restored by increasing intracellular calcium buffering capacity with EGTA-AM, implying close coupling of Ca -channels to SVs was compromised. Acute restoration of ATP to physiological levels in the presynaptic terminal did not revert synaptic defects. Loss of DRP1 impairs mitochondrial morphology in the presynaptic terminal, which in turn seems to arrest synaptic maturation. Impaired mitochondrial biogenesis and function is implicated in many neurodegenerative diseases, and likely affects synaptic neurotransmission prior to cellular loss. Dynamin-related protein 1 (DRP1) is essential for mitochondrial fissi...
Indirect results in humans suggest that chronic overfeeding decreases physical activity with few ... more Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels. C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9-11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity. 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: < 0.0001; female: < 0.0001) and had significantly higher body fat (male: < 0.0001; female: < 0.0001). The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male ( = 0.05, 70 ± 28%) and female mice ( = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat. Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones.
This study characterizes the mechanisms underlying defects in synaptic transmission when DRP1 is ... more This study characterizes the mechanisms underlying defects in synaptic transmission when DRP1 is genetically eliminated. Viral-mediated knockout of DRP1 from the presynaptic terminal at the mouse calyx of Held increased initial release probability, reduced the size of synaptic vesicle recycling pool, and impaired synaptic vesicle recycling. Transmission defects could be partially restored by increasing intracellular calcium buffering capacity with EGTA-AM, implying close coupling of Ca -channels to SVs was compromised. Acute restoration of ATP to physiological levels in the presynaptic terminal did not revert synaptic defects. Loss of DRP1 impairs mitochondrial morphology in the presynaptic terminal, which in turn seems to arrest synaptic maturation. Impaired mitochondrial biogenesis and function is implicated in many neurodegenerative diseases, and likely affects synaptic neurotransmission prior to cellular loss. Dynamin-related protein 1 (DRP1) is essential for mitochondrial fissi...
Indirect results in humans suggest that chronic overfeeding decreases physical activity with few ... more Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels. C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9-11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity. 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: < 0.0001; female: < 0.0001) and had significantly higher body fat (male: < 0.0001; female: < 0.0001). The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male ( = 0.05, 70 ± 28%) and female mice ( = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat. Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones.
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