bims-empneu Biomed News
on Exercise and Molecular Pathways Involved in Neuroprotection
Issue of 2021‒04‒04
ten papers selected by
Navabeh Zare-Kookandeh
Victoria University

  1. Front Aging Neurosci. 2021 ;13 615247
      Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators. Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50-70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)]. Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits. Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men.
    Keywords:  brain volume; cognition; exercise; fitness; molecular biomarkers; psychological health
  2. Med Sci Sports Exerc. 2021 Mar 25.
      INTRODUCTION: The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural MRI. Critically, microstructural alterations within the hippocampus over short time intervals are associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. However, it is not yet known if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise.METHODS: We used a within subject-design to determine if a 30-minute bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging (DTI) measures in healthy older adults (n=30) compared to a seated rest control condition.
    RESULTS: Significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) were found after exercise relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity (Dr). No significant differences in axial diffusivity (Da) were observed.
    CONCLUSION: These findings suggest that a single exercise session can lead to microstructural alterations in the hippocampus of healthy older adults. These differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations resulting from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus.
  3. Int J Mol Sci. 2021 Mar 16. pii: 3003. [Epub ahead of print]22(6):
      Stroke-induced cognitive impairments affect the long-term quality of life. High-intensity interval training (HIIT) is now considered a promising strategy to enhance cognitive functions. This review is designed to examine the role of HIIT in promoting neuroplasticity processes and/or cognitive functions after stroke. The various methodological limitations related to the clinical relevance of studies on the exercise recommendations in individuals with stroke are first discussed. Then, the relevance of HIIT in improving neurotrophic factors expression, neurogenesis and synaptic plasticity is debated in both stroke and healthy individuals (humans and rodents). Moreover, HIIT may have a preventive role on stroke severity, as found in rodents. The potential role of HIIT in stroke rehabilitation is reinforced by findings showing its powerful neurogenic effect that might potentiate cognitive benefits induced by cognitive tasks. In addition, the clinical role of neuroplasticity observed in each hemisphere needs to be clarified by coupling more frequently to cellular/molecular measurements and behavioral testing.
    Keywords:  angiogenesis; cerebral ischemia; cognition; endurance exercise; neurogenesis; neurotrophic factors; rat and human model; stroke rehabilitation
  4. Int J Environ Res Public Health. 2021 Mar 30. pii: 3593. [Epub ahead of print]18(7):
      Acute high-intensity interval training (HIIT) is a time-efficient strategy to improve physical health; however, the effect of acute HIIT on executive function (EF) is unclear. The aim of this study was to systematically review the existing evidence and quantify the effect of acute HIIT on overall EF and the factors affecting the relationship between acute HIIT and EF. Standard databases (i.e., the PubMed, Medline, Scopus, and CENTRAL databases) were searched for studies that examined the effect of acute HIIT on EF and were published up until January 2021. The overall EF and factors grouped by three categories, namely, EF assessment characteristics, exercise intervention characteristics, and sample and study characteristics, were analyzed by percentage of comparison for positive or null/negative effects. Overall, 35 of 57 outcomes (61%) across 24 studies revealed that acute HIIT has a positive effect on overall EF. In terms of factors, the results indicated that among EF assessment characteristics, groups, inhibition, updating, and the assessment occurring within 30 min may moderate the effect of acute HIIT on EF, while among exercise intervention characteristics, total time within 11 to 30 min may moderate the effect. Finally, among sample characteristics, age under 40 years may moderate the effect. Acute HIIT is generally considered a viable alternative for eliciting EF gains, with factors related to EF components, timing of the assessment, exercise total time, and age potentially moderating the effect of HIIT on EF.
    Keywords:  acute exercise; cognitive function; executive function; exercise; high-intensity interval training; systematic review
  5. Life (Basel). 2021 Mar 30. pii: 292. [Epub ahead of print]11(4):
      Cardiorespiratory fitness (CRF) is assumed to exert beneficial effects on brain structure and executive control (EC) performance. However, empirical evidence of exercise-induced cognitive enhancement is not conclusive, and the role of CRF in younger adults is not fully understood. Here, we conducted a study in which healthy young adults took part in a moderate aerobic exercise intervention program for 9 weeks (exercise group; n = 48), or control condition of non-aerobic exercise intervention (waitlist control group; n = 72). Before and after the intervention period maximal oxygen uptake (VO2max) as an indicator of CRF, the Flanker task as a measure of EC performance and grey matter volume (GMV), as well as cortical thickness via structural magnetic resonance imaging (MRI), were assessed. Compared to the control group, the CRF (heart rate, p < 0.001; VO2max, p < 0.001) and EC performance (congruent and incongruent reaction time, p = 0.011, p < 0.001) of the exercise group were significantly improved after the 9-week aerobic exercise intervention. Furthermore, GMV changes in the left medial frontal gyrus increased in the exercise group, whereas they were significantly reduced in the control group. Likewise, analysis of cortical morphology revealed that the left lateral occipital cortex (LOC.L) and the left precuneus (PCUN.L) thickness were considerably increased in the exercise group, which was not observed in the control group. The exploration analysis confirmed that CRF improvements are linked to EC improvement and frontal grey matter changes. In summary, our results support the idea that regular endurance exercises are an important determinant for brain health and cognitive performance even in a cohort of younger adults.
    Keywords:  aerobic fitness; cortical thickness; executive control; exercise intervention; grey matter; randomized controlled trial
  6. Biosci Rep. 2021 Mar 30. pii: BSR20204284. [Epub ahead of print]
      BACKGROUND: Fatigue can be induced after acceleration exposure, however the mechanism of it is still unclear. The aim of the present study was to examine whether metabolites changes can decrease cognitive and physical function after acceleration.METHODS: Graybiel scale and Fatigue Self-rating scale were used to assess the seasickness and fatigue degrees of eighty-seven male seafarers respectively after sailing. To test the effect of pyruvate on cognitive and physical functions, five different doses of pyruvate were administrated into rats. Insulin can reduce the accumulation of pyruvate. To observe the insulin effect on pyruvate, and cognitive, physical functions after acceleration, insulin administration or treatment of promoting insulin secretion was used. Physical and cognitive functions were assessed using Open Field test, Morris water maze and Loaded swimming test in animals.
    RESULTS: Physical and cognitive abilities were decreased obviously, and Serum pyruvate level increased mostly in human and rats after acceleration. Compared to vehicle group, physical and cognitive abilities were significantly decreased after pyruvate administration. Besides, we found a significant decline in adenosine triphosphate concentration and pyruvate dehydrogenase activity in the hippocampus, prefrontal cortex, liver, and muscle of rats treated with acceleration or pyruvate injection, while insulin administration or treatment of promoting insulin secretion markedly alleviated this decline and the impairment of physical and cognitive abilities, compared to the control group.
    CONCLUSION: Our results indicates that pyruvate has a negative effect on physical and cognitive abilities after acceleration. Insulin can inhibit pyruvate accumulation and cognitive and physical function after acceleration exposure.
    Keywords:  acceleration exposure; insulin; physical and cognitive abilities; pyruvate
  7. Neurol Neuroimmunol Neuroinflamm. 2021 May;pii: e982. [Epub ahead of print]8(3):
      OBJECTIVE: To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS).METHODS: Sixty-nine pwMS (Expanded Disability Status Scale score 3.0-6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention.
    RESULTS: Acute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT.
    CONCLUSION: Future studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS.
    CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS.
    TRIAL REGISTRATION INFORMATION: Clinical trial registration number: NCT03652519.
  8. Int J Mol Sci. 2021 Mar 12. pii: 2897. [Epub ahead of print]22(6):
      Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD.
    Keywords:  Alzheimer’s disease; amyloid-β peptide; molecular pathways; physical exercise; tau protein
  9. Exp Gerontol. 2021 Mar 24. pii: S0531-5565(21)00095-4. [Epub ahead of print] 111320
      BACKGROUND: Deterioration of neuromuscular function is a major mechanism of age-related strength loss. Resistance training (RT) improves muscle strength and mass. However, the effects of RT on neuromuscular adaptations in middle-aged and older adults are unclear.METHODS: Randomised controlled RT interventions (≥2 weeks) involving adults aged ≥50 years were identified. Primary outcome measures were voluntary activation (VA), electromyographic (EMG) activity during maximal voluntary contraction (MVC), and antagonist coactivation. Data were pooled using a weighted random-effect model. Sub-analyses were conducted by muscle or muscle group and health status of participants. Sensitivity analysis was based on study quality. P < 0.05 indicated statistical significance.
    RESULTS: Twenty-seven studies were included. An effect was found for VA (standardised mean difference [SMD] 0.54, 0.01 to 1.07, P = 0.04), This result remained significant following sensitivity analysis involving only studies that were low risk of bias. Subgroup analyses showed an effect for plantar flexor VA (SMD 1.13, 0.20 to 2.06, P = 0.02) and VA in healthy participants (SMD 1.04, 0.32 to 1.76, P = 0.004). There was no effect for EMG activity or antagonist coactivation of any muscle group (P > 0.05).
    DISCUSSION: Resistance training did not alter EMG activity or antagonist coactivation in older adults. Sensitivity analysis resulted in the effect for VA remaining significant, indicating that this finding was not dependent on study quality. Studies predominantly involved healthy older adults (78%), limiting the generalisability of these findings to clinical cohorts. Future research should determine the effects of RT on neuromuscular function in people with sarcopenia and age-related syndromes.
    Keywords:  Ageing; Muscle activation; Neuromuscular; Resistance training