bims-empneu Biomed News
on Exercise and Molecular Pathways Involved in Neuroprotection
Issue of 2021–03–14
four papers selected by
Navabeh Zare-Kookandeh, Victoria University



  1. Front Cell Neurosci. 2021 ;15 640724
      Background: Exercise training induces beneficial effects on neurodegenerative diseases, and specifically on multiple sclerosis (MS) and it's model experimental autoimmune encephalomyelitis (EAE). However, it is unclear whether exercise training exerts direct protective effects on the central nervous system (CNS), nor are the mechanisms of neuroprotection fully understood. In this study, we investigated the direct neuroprotective effects of high-intensity continuous training (HICT) against the development of autoimmune neuroinflammation and the role of resident microglia. Methods: We used the transfer EAE model to examine the direct effects of training on the CNS. Healthy mice performed HICT by treadmill running, followed by injection of encephalitogenic proteolipid (PLP)-reactive T-cells to induce EAE. EAE severity was assessed clinically and pathologically. Brain microglia from sedentary (SED) and HICT healthy mice, as well as 5-days post EAE induction (before the onset of disease), were analyzed ex vivo for reactive oxygen species (ROS) and nitric oxide (NO) formation, mRNA expression of M1/M2 markers and neurotrophic factors, and secretion of cytokines and chemokines. Results: Transfer of encephalitogenic T-cells into HICT mice resulted in milder EAE, compared to sedentary mice, as indicated by reduced clinical severity, attenuated T-cell, and neurotoxic macrophage/microglial infiltration, and reduced loss of myelin and axons. In healthy mice, HICT reduced the number of resident microglia without affecting their profile. Isolated microglia from HICT mice after transfer of encephalitogenic T-cells exhibited reduced ROS formation and released less IL-6 and monocyte chemoattractant protein (MCP) in response to PLP-stimulation. Conclusions: These findings point to the critical role of training intensity in neuroprotection. HICT protects the CNS against autoimmune neuroinflammation by reducing microglial-derived ROS formation, neurotoxicity, and pro-inflammatory responses involved in the propagation of autoimmune neuroinflammation.
    Keywords:  autoimmunity; exercise training; experimental autoimmune encephalomyelitis; microglia; multiple sclerosis; neuroprotection
    DOI:  https://doi.org/10.3389/fncel.2021.640724
  2. J Gerontol A Biol Sci Med Sci. 2021 Mar 04. pii: glab067. [Epub ahead of print]
       BACKGROUND: Physical inactivity is a risk factor for type 2 diabetes (T2D) and dementia. However, it is unknown if physical activity (PA) intensity is associated with brain health in people with T2D. Therefore, this study aimed to determine 1) associations between PA intensity and step count with both cognition and brain structure and 2) if apolipoprotein E-ε4 (APOE-ε4) or insulin-therapy modifies any associations.
    METHODS: Participants were people with T2D (n=220; aged 55-86 years). An accelerometer worn over the left hip was used to obtain step count and moderate-to-vigorous PA (MVPA) averaged over 7 days. Cognition in 7 domains was obtained using a battery of neuropsychological tests. Brain structure was measured by Magnetic Resonance Imaging (MRI). Linear regression models were used to examine associations between step count, MVPA and each cognitive and MRI measure. APOE-ε4 x PA and insulin-therapy x PA product terms were added to the models to examine effect modification.
    RESULTS: The mean age of participants was 67.9 (SD 6.3). Higher step count was associated with greater hippocampal volume (β=0.028 95%CI 0.005, 0.051). Insulin-therapy modified the association between MVPA and attention-processing speed, such that associations were significant in people receiving insulin-therapy (P for interaction=0.019). There were no other significant associations.
    CONCLUSIONS: Higher step count and greater time spent in MVPA may be associated with better hippocampal volume and attention-processing speed respectively in people with T2D. People with greater diabetes severity (receiving insulin-therapy) may get more cognitive benefit from MVPA.
    Keywords:  Physical activity intensity; brain atrophy; cognitive decline; dementia; walking
    DOI:  https://doi.org/10.1093/gerona/glab067
  3. Behav Cogn Psychother. 2021 Mar 08. 1-15
       BACKGROUND: Cognitive behavioural therapy (CBT) is currently the treatment of choice for most anxiety disorders. Yet, with recovery rates of approximately 50%, many patients fail to achieve complete remission. This has led to increased efforts to enhance treatment efficacy. Physical exercise (PE) has in recent years been advocated as means to augment the effects of CBT for anxiety disorders. PE appears to reduce anxiety through other mechanisms than CBT, some of which might also have the potential to augment the effects of psychological treatment.
    AIMS: The current review aimed to summarize and discuss the current research status on CBT augmented with PE for anxiety.
    METHOD: A systematic literature search was conducted in the databases PsychInfo, Medline and Web of Science to evaluate the potential augmentative effect of combining PE with CBT for anxiety disorders. These effects were intended to be evaluated in a meta-analysis, but findings from the few and diverse studies were better summarized in a systematic review.
    RESULTS: Eight articles were included in this review, of which two had no control group, while six had from two to four experimental arms. Six of the studies concluded in favour of benefits of add-on PE, while two studies found no added benefits of the combined interventions.
    CONCLUSIONS: The combination of PE and CBT appears feasible. Add-on PE seems to be more beneficial for clinical populations, when administered regularly several times per week, across several weeks. Future studies should investigate further how and for whom to best combine PE and CBT.
    Keywords:  CBT; anxiety; cognitive behavioural therapy; physical exercise
    DOI:  https://doi.org/10.1017/S1352465821000126
  4. Front Aging Neurosci. 2021 ;13 589299
       Background: It has been suggested that physical inactivity and lack of stimulating cognitive activity are the two most significant modifiable risk factors to impair cognitive function. Although many studies that investigated the cognitive effects of physical exercise and cognitive stimuli in dual-task conditions showed improved cognitive performance, others have not confirmed these findings. The main aim of the present work is to analyze the effects of a dual-task multimodal physical exercise training, at moderate intensity, and cognitive stimulation on cognitive and physical function in healthy older adults.
    Methods: This clinical trial was registered on the Brazilian Registry of Clinical Trials (RBR-9zrx3d). Here we tested the effects of a dual-task multimodal physical exercise training, at moderate intensity, on cognitive and physical function and quality of life in community dwelling older adults. The training protocol included 24 group sessions, 2/week, per 75 min. Cognition was assessed using CANTAB automated neuropsychological tests and Functional Capacity to Exercise tests. Performance was compared from baseline to post intervention and to a non-exercise control group using Mixed Linear Model for repeated measures.
    Results: Control (CG) and dual-task (DTEx) groups progressed differentially over time on performance of episodic memory, sustained visual attention, functional mobility, cardiorespiratory fitness, lower limbs strength resistance, agility, quality of life and dual-task performance with significant improved DTEx performance. Control group did not show any significant changes on these tests except for showing a reduction in dual-task performance.
    Conclusion: We suggest that the dual-task combination of multisensory cognitive stimulation and multimodal moderate physical exercise training, twice a week, may be adopted as an effective program to reduce progression of age-related cognitive decline and improve physical fitness and quality of life on healthy older adults.
    Clinical Trial Registration: Brazilian Registry of Clinical Trials: https://ensaiosclinicos.gov.br/rg/RBR-9zrx3d -UTN code: U1111-1233-6349.
    Keywords:  aged; cognitive dysfunction; dual-task exercise; healthy aging; neuropsychological tests; physical fitness; physical therapy modalities; rehabilitation
    DOI:  https://doi.org/10.3389/fnagi.2021.589299