bims-empneu Biomed News
on Exercise and Molecular Pathways Involved in Neuroprotection
Issue of 2021‒03‒07
ten papers selected by
Navabeh Zare-Kookandeh
Victoria University

  1. Front Cell Neurosci. 2021 ;15 598230
      While it is well-known that pre-stroke exercise conditioning reduces the incidence of stroke and the development of comorbidities, it is unclear whether post-stroke exercise conditioning is also neuroprotective. The present study investigated whether exercise postconditioning (PostE) induced neuroprotection and elucidated the involvement of SIRT1 regulation on the ROS/ER stress pathway. Adult rats were subjected to middle cerebral artery occlusion (MCAO) followed by either: (1) resting; (2) mild exercise postconditioning (MPostE); or (3) intense exercise postconditioning (IPostE). PostE was initiated 24 h after reperfusion and performed on a treadmill. At 1 and 3 days thereafter, we determined infarct volumes, neurological defects, brain edema, apoptotic cell death through measuring pro- (BAX and Caspase-3) and anti-apoptotic (Bcl-2) proteins, and ER stress through the measurement of glucose-regulated protein 78 (GRP78), inositol-requiring 1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), Caspase-12, and SIRT1. Proteins were measured by Western blot. ROS production was detected by flow cytometry.Compared to resting rats, both MPostE and IPostE significantly decreased brain infarct volumes and edema, neurological deficits, ROS production, and apoptotic cell death. MPostE further increased Bcl-2 expression and Bcl-2/BAX ratio as well as BAX and Caspase-3 expressions and ROS production (*p < 0.05). Both PostE groups saw decreases in ER stress proteins, while MPostE demonstrated a further reduction in GRP78 (***p < 0.001) and Caspase-12 (*p < 0.05) expressions at 1 day and IRE1α (**p < 0.01) and CHOP (*p < 0.05) expressions at 3 days. Additionally, both PostE groups saw significant increases in SIRT1 expression.In this study, both mild and intense PostE levels induced neuroprotection after stroke through SIRT1 and ROS/ER stress pathway. Additionally, the results may provide a base for our future study regarding the regulation of SIRT1 on the ROS/ER stress pathway in the biochemical processes underlying post-stroke neuroprotection. The results suggest that mild exercise postconditioning might play a similar neuroprotective role as intensive exercise and could be an effective exercise strategy as well.
    Keywords:  CHOP; ER stress; apoptosis; caspase-12; exercise intensity; ischemia/reperfusion
  2. Int J Geriatr Psychiatry. 2021 Feb 16.
      BACKGROUND: Physical exercise is effective in protecting against age-related neurodegeneration and cognitive decline. Although there are many neuroimaging studies to evaluate the effect of physical exercise on aging brains, consistent conclusions are limited due to the wide variety of measuring techniques and small sample sizes.OBJECTIVE: Identify brain regions that show exercise-induced neuroplasticity consistently across various imaging modalities and correlate regional neuroplasticity with cognitive changes in older adults.
    METHODS: An electronic literature search for randomized controlled trials with magnetic resonance imaging measures was performed. We conducted a series of quantitative meta-analyses using activation likelihood estimation on included studies with voxel-based neuroimaging findings. Nonvoxelbased findings were summarized as a descriptive review.
    RESULTS: Out of 839 publications identified from the literature search, 30 experiments including 2670 participants from 22 papers met the criteria of meta-analyses. Overall, physical exercise consistently results in structural and functional changes in the hippocampus/parahippocampusl area and a cluster within the cerebellum. Although changes of medial/superior prefrontal cortex did not pass the stringent threshold, they were associated with cognitive changes.
    CONCLUSIONS: This study highlights the effectiveness of physical exercise in inducing hippocampus plasticity, which may be crucially relevant for maintaining memory function in older adults.
    Keywords:  activation-likelihood estimation (ALE); aging; hippocampus; magnetic resonance imaging (MRI); physical exercise
  3. J Physiol. 2021 Feb 28.
    Keywords:  ageing; cerebral blood flow; cerebrovascular function; cognition; physical activity; sedentary behaviour
  4. Mol Neurobiol. 2021 Feb 28.
      Brain iron increases with age and abnormal brain iron metabolism is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD). The iron-regulatory effect of furin, a ubiquitously expressed proconvertase, might play an important role in AD. Therefore, there is an urgent need to study the effect of furin on iron regulation in AD. For that purpose, we aimed to determine the role of physical exercise in AD associated with brain iron dyshomeostasis. Treadmill exercise attenuated the AD-related abnormal brain iron regulation by furin in vivo, as demonstrated via experiments in aged APP-C105 mice. Next, we examined whether treadmill exercise decreases excessive iron, directly affecting amyloid-β (Aβ) production through the regulation of α-secretase-dependent processing of amyloid protein precursor (APP) involved in the modulation of furin activity. We first observed that cognitive decline and Aβ-induced neuronal cell death were induced by disruption of APP processing via excess iron-induced disruption of furin activity in aged APP-C105 mice. The induced cognitive decline and cell death were attenuated by treadmill exercise. This result suggests that treadmill exercise alleviated cognitive decline and Aβ-induced neuronal cell death by promoting α-secretase-dependent processing of APP through low iron-induced enhancement of furin activity. This is concomitant with decreasing levels of lipid peroxidation products and promoting antioxidant defense enzyme capacities. Therefore, iron-targeted therapeutic strategies involving treadmill exercise might be useful for patients with AD.
    Keywords:  Alzheimer’s disease; Amyloid-β; Antioxidant defense enzymes. Treadmill exercise; Furin; Iron; Neuronal cell death
  5. Brain Struct Funct. 2021 Mar 06.
      Despite a growing number of functional MRI studies reporting exercise-induced changes during cognitive processing, a systematic determination of the underlying neurobiological pathways is currently lacking. To this end, our neuroimaging meta-analysis included 20 studies and investigated the influence of physical exercise on cognition-related functional brain activation. The overall meta-analysis encompassing all experiments revealed physical exercise-induced changes in the left parietal lobe during cognitive processing. Subgroup analysis further revealed that in the younger-age group (< 35 years old) physical exercise induced more widespread changes in the right hemisphere, whereas in the older-age group (≥ 35 years old) exercise-induced changes were restricted to the left parietal lobe. Subgroup analysis for intervention duration showed that shorter exercise interventions induced changes in regions connected with frontoparietal and default mode networks, whereas regions exhibiting effects of longer interventions connected with frontoparietal and dorsal attention networks. Our findings suggest that physical exercise interventions lead to changes in functional activation patterns primarily located in precuneus and associated with frontoparietal, dorsal attention and default mode networks.
    Keywords:  Brain health; Cognition; Exercise; Network
  6. Metabolites. 2021 Feb 16. pii: 111. [Epub ahead of print]11(2):
      Irisin is a myokine primarily secreted by skeletal muscles and is known as an exercise-induced hormone. The purpose of this study was to determine whether the PGC-1α -FNDC5 /Irisin-UCP1 expression which is an irisin-related signaling pathway, is activated by an acute swimming exercise. Fourteen to sixteen weeks old male C57BL/6J mice (n = 20) were divided into control (CON, n = 10) and swimming exercise groups (SEG, n = 10). The SEG mice performed 90 min of acute swimming exercise, while control (non-exercised) mice were exposed to shallow water (2 cm of depth) for 90 min. The mRNA and protein expression of PGC-1α, FNDC5 and browning markers including UCP1 were evaluated by quantitative real-time PCR and western blotting. Serum irisin concentration was measured by enzyme-linked immunosorbent assay. An acute swimming exercise did not lead to alterations in the mRNA and protein expression of PGC-1α in both soleus and gastrocnemius muscles, the mRNA and protein expression of UCP1 in brown adipose tissue, mRNA browning markers in visceral adipose tissue and circulating irisin when compared with the control group. On the other hand, an acute swimming exercise led to increases in the mRNA and protein expressions of FNDC5 in the soleus muscle, the protein expression of FNDC5 in the gastrocnemius muscles and the protein expression of UCP1 in subcutaneous adipose tissue.
    Keywords:  FNDC5; PGC-1α; UCP1; irisin; swimming exercise
  7. Int J Mol Sci. 2021 Feb 23. pii: 2199. [Epub ahead of print]22(4):
      Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and hyperglycemia. Chronic exposure to a T2DM microenvironment with hyperglycemia, hyperinsulinemia, oxidative stress and increased levels of proinflammatory mediators, has negative consequences to the cardiovascular system and mental health. Therefore, atherosclerotic cardiovascular diseases (CVD) and mental health issues have been strongly associated with T2DM. Lifestyle modifications, including physical exercise training, are necessary to prevent T2DM development and its associated complications. It is widely known that the regular practice of exercise provides several physiological benefits to subjects with T2DM, such as managing glycemic and blood pressure levels. Different types of exercise, from aerobic to resistance training, are effective to improve mental health and cognitive function in T2DM. Irisin is a myokine produced in response to exercise, which has been pointed as a relevant mechanism of action to explain the benefits of exercise on cardiovascular and mental health in T2DM patients. Here, we review emerging clinical and experimental evidence about exercise-linked irisin consequences to cardiovascular and mental health in T2DM.
    Keywords:  cognitive decline; dementia; inflammation; insulin resistance; memory; physical activity
  8. Life (Basel). 2021 Feb 23. pii: 173. [Epub ahead of print]11(2):
      Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia.
    Keywords:  cognitive impairment; exerkines; myokines; sarcopenic; skeletal muscle
  9. Neurobiol Aging. 2021 Feb 03. pii: S0197-4580(21)00032-4. [Epub ahead of print]101 230-246
      Exercise interventions have been shown to positively impact cognitive function in older adults, but the mechanisms underlying the neuroprotective effects of exercise on the brain are not well understood. Here, we aimed to synthesize and quantitatively analyze the current literature on exercise interventions and brain volume change in older adults and to examine the impact of key demographic and intervention features as well as study quality. This study was pre-registered with PROSPERO (CRD42018091866). EBSCOhost, Cochrane Library, Embase, and reference lists were searched to identify randomized-controlled trials (RCTs) of exercise interventions for healthy older adults and older adults (60+) with mild cognitive impairment (MCI). A total of 69 effects from 14 studies were pooled and expressed as Hedge's g using a random-effects model. Results indicated that there was no significant difference in brain volume outcomes for older adults that completed an exercise intervention compared to older adults in control groups (g = 0.012, p = 0.728, 95% CI = -0.055, .078). These results were confirmed using multilevel analysis to account for nesting of effects within studies (g = 0.009, p = 0.826, 95% CI = -0.072, 0.090) and using conservative post-hoc models to address possible non-independence of multiple outcome domains and sample nonindependence. No significant heterogeneity was detected, limiting moderator analyses. The implications for future research are discussed.
    Keywords:  Aging; Brain volume; Exercise; Meta-analysis; Randomized-controlled trials
  10. Sheng Li Xue Bao. 2021 Feb 25. 73(1): 126-136
      High-intensity interval training (HIIT) has proven to be a time-saving and efficient exercise strategy. Compared with traditional aerobic exercise, it can provide similar or even better health benefits. In recent years, a number of studies have suggested that HIIT could be used as a potential exercise rehabilitation therapy to improve cognitive impairment caused by obesity, diabetes, stroke, dementia and other diseases. HIIT may be superior to regular aerobic exercise. This article reviews the recent research progress on HIIT with a focus on its beneficial effect on brain cognitive function and the underlying mechanisms. HIIT may become an effective exercise for the prevention and/or improvement of brain cognitive disorder.