Biology subjects

Bennett, W.

Publications and source records attributed to Bennett, W..

4 recordsLinked to original sources

bioRxiv2026

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Initial Insights into the Dynamic Human Responses to Exercise

The goal of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to examine the physiological and molecular basis for health benefits in response to acute and chronic exercise. Prior to COVID-19 suspension, healthy, sedentary participants (N=206, 18-74y) were randomized to endurance exercise (N=80), resistance exercise (N=81), or non-exercise control (N=45) interventions. The prescribed vigorous acute endurance and resistance exercise bouts induced physiological and metabolic perturbations relative to resting homeostasis. The supervised chronic (3d/wk, 12wk) endurance or resistance training programs robustly improved several physiological parameters (i.e., VO2peak, muscular strength). Temporal biospecimen (blood, muscle, and adipose) collections and processing coupled to the acute exercise bouts were highly successful. In most cases, over 90% success was achieved for blood, muscle, and adipose samples. Endurance and resistance exercise induced distinct acute and chronic physiological responses, which provide a framework to interrogate the molecular basis for health adaptations to these two popular exercise modalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/705347v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@554ee9org.highwire.dtl.DTLVardef@afb28dorg.highwire.dtl.DTLVardef@f381cdorg.highwire.dtl.DTLVardef@cef19c_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

HDAC6 inhibition as a mechanism to prevent axon degeneration in the mSOD1G93A mouse model of ALS.

The loss of upper and lower motor neurons, and their axons is central to the loss of motor function and death in amyotrophic lateral sclerosis (ALS). Due to the diverse range of genetic and environmental factors that contribute to the pathogenesis of ALS, there have been difficulties in developing effective therapies for ALS. One dichotomy emerging in the field is that protection of the neuronal cell soma itself does not prevent axonal vulnerability and degeneration, suggesting the need for targeted therapeutics to prevent axon degeneration. Post-translational modifications of protein acetylation can alter the function, stability and half-life of individual proteins, and can be enzymatically modified by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), which add, or remove acetyl groups, respectively. Maintenance of post-translational microtubule acetylation has been suggested as a potential mechanism to stabilise axons and prevent axonal loss and neurodegeneration in ALS. This study has utilized an orally dosed HDAC6 specific inhibitor, ACY-738, prevent deacetylation and stabilize microtubules in the mSOD1G93A mouse model of ALS. Furthermore, co-treatment with riluzole was performed to determine any effects or drug interactions and potentially enhance preclinical research translation. This study shows ACY-738 treatment increased acetylation of microtubules in the spinal cord of mSOD1G93A mice, reduced lower motor neuron degeneration in the lumbar spinal cord of female mice, ameliorated reduction in peripheral nerve axon puncta size, but did not prevent overt motor function decline. The current study also shows peripheral nerve axon puncta size to be partially restored after treatment with riluzole and highlights the importance of co-treatment to measure the potential effects of therapeutics in ALS. HighlightsO_LIACY-738 inhibits HDAC6 and leads to increased microtubule acetylation in spinal cord of mSOD1G93A mice. C_LIO_LIACY-738 treatment reduces lower motor neuron degeneration in the lumbar spinal cord of mSOD1G93A mice. C_LIO_LIACY-738 treatment restores peripheral nerve axon puncta size of mSOD1G93A mice. C_LIO_LIACY-738 treatment does not prevent overt motor function decline mSOD1G93A mice. C_LIO_LIRiluzole treatment partially restores peripheral nerve axon puncta size in mSOD1G93A mice. C_LI

neuroscience↗

bioRxiv2021

Low intensity repetitive transcranial magnetic stimulation drives structural synaptic plasticity in the young and aged motor cortex.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool commonly used to drive neural plasticity in the young adult and aged brain. Recent data from mouse models have shown that even at subthreshold intensities (0.12 Tesla), rTMS can drive neuronal and glial plasticity in the motor cortex. However, the physiological mechanisms underlying subthreshold rTMS induced plasticity and whether these are altered with normal ageing are unclear. ObjectiveTo assess the effect of subthreshold rTMS, using the intermittent theta burst stimulation (iTBS) protocol on structural synaptic plasticity in the mouse motor cortex of young and aged mice. MethodsLongitudinal in vivo 2-photon microscopy was used to measure changes to the structural plasticity of pyramidal neuron dendritic spines in the motor cortex following a single train of subthreshold rTMS (in young adult and aged animals) or the same rTMS train administered on 4 consecutive days (in young adult animals only). Data were analysed with Bayesian hierarchical generalized linear regression models and interpreted with the aid of Bayes Factors (BF). ResultsWe found strong evidence (BF>10) that subthreshold rTMS altered the rate of dendritic spine losses and gains, dependent on the number of stimulation sessions and that a single session of subthreshold rTMS was effective in driving structural synaptic plasticity in both young adult and aged mice. ConclusionThese findings provide further evidence that rTMS drives synaptic plasticity in the brain and uncovers structural synaptic plasticity as a key mechanism of subthreshold rTMS induced plasticity.

neuroscience↗

bioRxiv2021

Machine Learning to Summarize and Provide Context for Sleep and Eating Schedules.

The relative timing of sleep and of eating within the circadian day is important for human health. Despite much data on sleep, and a growing data set for eating, there remains a need for an interpretative framework for the understanding of this data for health decisions. This study provides a new statistical and machine learning analysis of more than 500 participants in the Daily24 project. From their data, and the analysis, we propose a framework for determining the classification of participants into different chronotypes and with that the ability to realize the potential impact of daily circadian habits on health. We propose that our resulting distribution curves could be used, similar to NHANES (National Health and Nutrition Examination Survey) data for pediatric growth, as a measure for circadian misalignment and used to help guide re-entrainment schedules. Author summaryDaily habits can be positive, negative or neutral for human health. Generally sleep and eating schedules are assumed without thought for their potential to help or interfere with health. In this study we propose a framework, based on data from more than 500 participants, for evaluating the relative timing of meals and sleep schedules. This evaluation, similar to pediatric growth charts, can guide clinical suggestions for those at the extremes, while helping others to realize that they are unusual relative to the population average

bioinformatics↗