Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.

Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of hepatic ketone production on brain health during exercise, healthy 6-month-old female rats underwent viral knockdown of the rate-limiting enzyme in the liver that catalyses the first reaction in ketogenesis: 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2).

Hindlimb immobilization induces insulin resistance and elevates mitochondrial ROS production in the hippocampus of female rats.

Alzheimer's disease (AD) is the fifth leading cause of death in older adults, and treatment options are severely lacking. Recent findings demonstrate a strong relationship between skeletal muscle and cognitive function, with evidence supporting that muscle quality and cognitive function are positively correlated in older adults. Conversely, decreased muscle function is associated with a threefold increased risk of cognitive decline.

Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.

Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved.

Selective breeding for physical inactivity produces cognitive deficits altered hippocampal mitochondrial and synaptic function.

Physical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer's Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physical activity status of previous generations could play an important role in one's brain health and their subsequent risk for neurodegenerative diseases. Thus, our study aimed to test the hypothesis that selective breeding for physical inactivity, or for high physical activity, preference produces heritable deficits and enhancements to brain health, respectively.

Proceedings from the Albert Charitable Trust Inaugural Workshop on 'Understanding the Acute Effects of Exercise on the Brain'.

An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases.

Acute Wheel-Running Increases Markers of Stress and Aversion-Related Signaling in the Basolateral Amygdala of Male Rats.

Physical activity (PA) is a non-invasive, cost-effective means of reducing chronic disease. Most US citizens fail to meet PA guidelines, and individuals experiencing chronic stress are less likely to be physically active. To better understand the barriers to maintaining active lifestyles, we sought to determine the extent to which short- versus long-term PA increases stress- and aversion-related markers in wild-type (WT) and low voluntary running (LVR) rats, a unique genetic model of low physical activity motivation.

Transcriptomic analysis reveals novel molecular signaling networks involved in low voluntary running behavior after AP-1 inhibition.

Understanding the neuro-molecular mechanisms that mediate the quantity of daily physical activity (PA) level is of medical significance, given the tremendous health benefits associated with greater physical activity. Here, we examined the effects of intra-nucleus accumbens (NAc) inhibition of activator protein-1 (AP-1), an important transcriptional factor downstream of cAMP response element binding protein (CREB; a reward-related transcriptional regulator), on voluntary wheel running behavior in wild-type (WT) and low voluntary running (LVR) female rats. Transcriptome analysis of the nucleus accumbens (NAc; a brain region critical for PA reward and motivation) was performed to further determine molecular responses to intra-NAc AP-1 inhibition in these rat lines.

Contributions of physical inactivity and sedentary behavior to metabolic and endocrine diseases.

Physical inactivity is the fourth leading global cause of death and is a major contributor to metabolic and endocrine diseases. In this review we provide a current update of the past 5 years in the field as it pertains to the most prevalent and deadly chronic diseases. Despite the prevalence of physical inactivity in modern society, it remains largely overlooked relative to other comparable risk factors such as obesity, and our molecular understanding of how physical inactivity impacts metabolism is still partially unknown.

Hepatocyte-specific eNOS deletion impairs exercise-induced adaptations in hepatic mitochondrial function and autophagy.

Objective: Endothelial nitric oxide synthase (eNOS) is a potential mediator of exercise-induced hepatic mitochondrial adaptations.

Methods: Here, male and female hepatocyte-specific eNOS knockout (eNOS ) and intact hepatic eNOS (eNOS ) mice performed voluntary wheel-running exercise (EX) or remained in sedentary cage conditions for 10 weeks.

Results: EX resolved the exacerbated hepatic steatosis in eNOS male mice.

Resistance-exercise training attenuates LPS-induced astrocyte remodeling and neuroinflammatory cytokine expression in female Wistar rats.

Neuroinflammation is an early detectable marker of mild cognitive impairment, the transition state between normal cognition and dementia. Resistance-exercise training can attenuate the cognitive decline observed in patients with mild cognitive impairment. However, the underlying mechanisms of resistance training effects are largely unknown.

Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing.

RNA-sequencing and behavioral testing reveals inherited physical inactivity co-selects for anxiogenic behavior without altering depressive-like behavior in Wistar rats.

Physical inactivity is positively associated with anxiety and depression. Considering physical inactivity, anxiety, and depression each have a genetic basis for inheritance, our lab used artificial selectively bred low-voluntary running (LVR) and wild type (WT) female Wistar rats to test if physical inactivity genes selected over multiple generations would lead to an anxiety or depressive-like phenotype. We performed next generation RNA sequencing and immunoblotting on the dentate gyrus to reveal key biological functions from heritable physical inactivity.

The role of nucleus accumbens CREB attenuation in rescuing low voluntary running behavior in female rats.

Given the integral role of nucleus accumbens (NAc) cAMP response element binding protein (CREB) activity in motivational processes, the goal of the current study was to determine whether blunting chronic NAc CREB activity could rescue the low physical activity motivation of female, low voluntary running (LVR) rats. NAc CREB phosphorylation is elevated in these rats, a state previously attributed to deficits in reward valuation. It was recently shown that overexpression of the upstream CREB inhibitor, protein kinase inhibitor alpha (PKIα), increased LVR nightly running by ~threefold.

Medial preoptic estrogen receptor-beta blunts the estrogen receptor-alpha mediated increases in wheel-running behavior of female rats.

Estrogens are believed to enhance rodent voluntary wheel-running through medial preoptic (mPOA) estrogen receptor α (ERα) signaling, with little role attributed to estrogen receptor β (ERβ). Systemic ERβ activation has been shown to mitigate ERα driven increases in wheel-running. Therefore, the present goal was to determine whether ERβ signaling in the mPOA plays a similar modulatory role over ERα.

Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.

Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported that skeletal muscle L1 expression is lower following acute and chronic exercise training in humans.

Resistance-exercise training ameliorates LPS-induced cognitive impairment concurrent with molecular signaling changes in the rat dentate gyrus.

Effective treatments preventing brain neuroinflammatory diseases are lacking. Resistance-exercise training (RT) ameliorates mild cognitive impairment (MCI), a forerunner to neuroinflammatory diseases. However, few studies have addressed the molecular basis by which RT abates MCI.

Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats.

Ketogenic diets (KDs) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise is unknown. We investigated the effects of a KD versus a "western" diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to 3 groups ( = 8-14 per group): standard chow (SC; 17% fat), WD (42% fat), or KD (90.

Rats Selectively Bred for High Voluntary Physical Activity Behavior are Not Protected from the Deleterious Metabolic Effects of a Western Diet When Sedentary.

Background: Physical activity and diet are well-established modifiable factors that influence chronic disease risk. We developed a selectively bred, polygenic model for high and low voluntary running (HVR and LVR, respectively) distances. After 8 generations, large differences in running distance were noted.

Voluntary wheel running effects on intra-accumbens opioid driven diet preferences in male and female rats.

Palatability driven feeding and voluntary physical activity are mediated by and influence similar neural mechanisms, notably through the actions of opioids within the nucleus accumbens. Recent studies suggest that access to a voluntary running wheel results in sex dependent behavioral and physiological adaptations related to opioid mediated palatability-driven feeding. To explore this relationship, male and female Wistar rats were given either access to a voluntary running wheel (RUN group) or no access (SED group) for one week prior to being stereotaxically implanted with bilateral cannulae targeting the nucleus accumbens.

Voluntary wheel running effects on intra-accumbens opioid high-fat feeding and locomotor behavior in Sprague-Dawley and Wistar rat strains.

The present study examined the influence of physical activity vs. sedentary home cage conditions on baseline and opioid-driven high-fat feeding behaviors in two common strains of laboratory rats. Sprague-Dawley and Wistar rats were singly housed with either access to a voluntary running wheel (RUN) or locked-wheel (SED) for 5 weeks, before being stereotaxically implanted with bilateral cannulae targeting the nucleus accumbens.

Sex dependent effects of physical activity on diet preference in rats selectively bred for high or low levels of voluntary wheel running.

Considering the current obesity epidemic is due in large part to an energy imbalance, it is crucial to explore biological mechanisms that mediate palatable high energy food intake and physical activity behavior levels. Previous research demonstrates a unique sex dependent influence of physical activity on diet preference, specifically changes in palatable high-fat diet intake. Therefore, factors of motivation may be underlying the differential effect of physical activity in male and female rats on their diet preference.

Correction to: Overexpression of Protein Kinase Inhibitor Alpha Reverses Rat Low Voluntary Running Behavior.

The original version of this article unfortunately contained mistake in Table 2 to where two directionality arrows were inverted.

Medial habenula maturational deficits associate with low motivation for voluntary physical activity.

The habenula is a small, diencephalic structure comprised of distinct subnuclei which receives inputs from the limbic forebrain and sends projections to various regions in the midbrain, making this region well positioned to influence reward and motivation. Genetic ablation of the dorsal medial habenula is known to decrease voluntary wheel-running in mice. However, the extent to which the medial habenula (MHb) mediates wheel-running motivation in the context of high or low motivation for voluntary physical activity remains to be determined.

Overexpression of Protein Kinase Inhibitor Alpha Reverses Rat Low Voluntary Running Behavior.

A gene was sought that could reverse low voluntary running distances in a model of low voluntary wheel-running behavior. In order to confirm the low motivation to wheel-run in our model does not result from defects in reward valuation, we employed sucrose preference and conditioned place preference for voluntary wheel-access. We observed no differences between our model and wild-type rats regarding the aforementioned behavioral testing.