bims-empneu 2021-07-04 papers

bims-empneu

Biomed News

on Exercise and Molecular Pathways Involved in Neuroprotection

Issue of 2021–07–04
nine papers selected by
Navabeh Zare-Kookandeh, Victoria University

The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection.
VO2peak Response Heterogeneity in Persons with Multiple Sclerosis: To HIIT or Not to HIIT?
Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications.
Neuroprotective Effects of Physical Activity via the Adaptation of Astrocytes.
Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches.
White matter plasticity in healthy older adults: The effects of aerobic exercise.
Irisin-Associated Neuroprotective and Rehabilitative Strategies for Stroke.
Endurance exercise improves avoidance learning and spatial memory, through changes in genes of GABA and relaxin-3, in rats.
Changes in cognitive control and mood across repeated exercise sessions.

Int J Mol Sci. 2021 Jun 17. pii: 6479. [Epub ahead of print]22(12):

The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection.

Johannes Burtscher, Grégoire P Millet, Nicolas Place, Bengt Kayser, Nadège Zanou.

  Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer's disease, or the most common neurodegenerative motor disorder, Parkinson's disease. While there is evidence that exercise induces signalling from skeletal muscle to the brain, the mechanistic understanding of the crosstalk along the muscle-brain axis is incompletely understood. Mitochondria in both organs, however, seem to be central players. Here, we provide an overview on the central role of mitochondria in exercise-induced communication routes from muscle to the brain. These routes include circulating factors, such as myokines, the release of which often depends on mitochondria, and possibly direct mitochondrial transfer. On this basis, we examine the reported effects of different modes of exercise on mitochondrial features and highlight their expected benefits with regard to neurodegeneration prevention or mitigation. In addition, knowledge gaps in our current understanding related to the muscle-brain axis in neurodegenerative diseases are outlined.

Keywords:  brain; exercise; mitochondria; muscle; myokines; neurodegeneration

DOI:  https://doi.org/10.3390/ijms22126479
Int J Sports Med. 2021 Jul 01.

VO2peak Response Heterogeneity in Persons with Multiple Sclerosis: To HIIT or Not to HIIT?

Marit Lea Schlagheck, Anika Wucherer, Annette Rademacher, Niklas Joisten, Sebastian Proschinger, David Walzik, Wilhelm Bloch, Jan Kool, Roman Gonzenbach, Jens Bansi, Philipp Zimmer.

Exercise is described to provoke enhancements of cardiorespiratory fitness in persons with Multiple Sclerosis (pwMS). However, a high inter-individual variability in training responses has been observed. This analysis investigates response heterogeneity in cardiorespiratory fitness following high intensity interval (HIIT) and moderate continuous training (MCT) and analyzes potential predictors of cardiorespiratory training effects in pwMS. 131 pwMS performed HIIT or MCT 3-5x/ week on a cycle ergometer for three weeks. Individual responses were classified. Finally, a multiple linear regression was conducted to examine potential associations between changes of absolute peak oxygen consumption (absolute ∆V̇O2peak/kg), training modality and participant's characteristics. Results show a time and interaction effect for ∆V̇O2peak/kg. Absolute changes of cardiorespiratory responses were larger and the non-response proportions smaller in HIIT vs. MCT. The model accounting for 8.6% of the variance of ∆V̇O2peak/kg suggests that HIIT, younger age and lower baseline fitness predict a higher absolute ∆V̇O2peak/kg following an exercise intervention. Thus, this work implements a novel approach that investigates potential determinants of cardiorespiratory response heterogeneity within a clinical setting and analyzes a remarkable bigger sample. Further predictors need to be identified to increase the knowledge about response heterogeneity, thereby supporting the development of individualized training recommendations for pwMS.

DOI: https://doi.org/10.1055/a-1481-8639
Cells. 2021 Jun 19. pii: 1548. [Epub ahead of print]10(6):

Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications.

Mustafa N Mithaiwala, Danielle Santana-Coelho, Grace A Porter, Jason C O'Connor.

  Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that 'fuel the fire' in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.

Keywords:  affective disorders; depression; kynurenine pathway; microglia; neurodegeneration; neuroinflammation; therapeutic strategies

DOI:  https://doi.org/10.3390/cells10061548
Cells. 2021 Jun 18. pii: 1542. [Epub ahead of print]10(6):

Neuroprotective Effects of Physical Activity via the Adaptation of Astrocytes.

Grazia Maugeri, Velia D'Agata, Benedetta Magrì, Federico Roggio, Alessandro Castorina, Silvia Ravalli, Michelino Di Rosa, Giuseppe Musumeci.

  The multifold benefits of regular physical exercise have been largely demonstrated in human and animal models. Several studies have reported the beneficial effects of physical activity, both in peripheral tissues and in the central nervous system (CNS). Regular exercise improves cognition, brain plasticity, neurogenesis and reduces the symptoms of neurodegenerative diseases, making timeless the principle of "mens sana in corpore sano" (i.e., a healthy mind in a healthy body). Physical exercise promotes morphological and functional changes in the brain, acting not only in neurons but also in astrocytes, which represent the most numerous glial cells in the brain. The multiple effects of exercise on astrocytes comprise the increased number of new astrocytes, the maintenance of basal levels of catecholamine, the increase in glutamate uptake, the major release of trophic factors and better astrocytic coverage of cerebral blood vessels. The purpose of this review is to highlight the effects of exercise on brain function, emphasize the role of astrocytes in the healthy CNS, and provide an update for a better understanding of the effects of physical exercise in the modulation of astrocyte function.

Keywords:  astrocytes; brain functions; exercise; neuron

DOI:  https://doi.org/10.3390/cells10061542
AIMS Neurosci. 2021 ;8(3): 357-389

Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches.

Kiran Kumar Siddappaji, Shubha Gopal.

  Alzheimer's disease (AD) is one of the most common, severe neurodegenerative brain disorder characterized by the accumulation of amyloid-beta plaques, neurofibrillary tangles in the brain causing neural disintegration, synaptic dysfunction, and neuronal death leading to dementia. Although many US-FDA-approved drugs like Donepezil, Rivastigmine, Galantamine are available in the market, their consumption reduces only the symptoms of the disease but fails in potency to cure the disease. This disease affects many individuals with aging. Combating the disease tends to be very expensive. This review focuses on biochemical mechanisms in the neuron both at normal and AD state with relevance to the tau hypothesis, amyloid hypothesis, the risk factors influencing dementia, oxidative stress, and neuroinflammation altogether integrated with neurodegeneration. A brief survey is carried out on available biomarkers in the diagnosis of the disease, drugs used for the treatment, and the challenges in approaching therapeutic targets in inhibiting the disease pathologies. This review conjointly assesses the demerits with the inefficiency of drugs to reach targets, their side effects, and toxicity. Optimistically, this review directs on the advantageous strategies in using nanotechnology-based drug delivery systems to cross the blood-brain barrier for improving the efficacy of drugs combined with a novel neuronal stem cell therapy approach. Determinately, this review aims at the natural, non-therapeutic healing impact of physical exercise on different model organisms and the effect of safe neuromodulation treatments using repetitive Transcranial Magnetic Stimulation (rTMS), transcranial Electrical Stimulation (tES) in humans to control the disease pathologies prominent in enhancing the synaptic function.

Keywords:  Alzheimer's disease; amyloid-beta plaques; dementia; neurodegeneration; neurofibrillary tangles; neuroinflammation; physical exercise

DOI:  https://doi.org/10.3934/Neuroscience.2021020
Neuroimage. 2021 Jun 24. pii: S1053-8119(21)00581-4. [Epub ahead of print]239 118305

White matter plasticity in healthy older adults: The effects of aerobic exercise.

Andrea Mendez Colmenares, Michelle W Voss, Jason Fanning, Elizabeth A Salerno, Neha P Gothe, Michael L Thomas, Edward McAuley, Arthur F Kramer, Agnieszka Z Burzynska.

  White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter.

Keywords:  Aerobic exercise; Aging; Clinical trial; Plasticity; White matter

DOI:  https://doi.org/10.1016/j.neuroimage.2021.118305
Neuromolecular Med. 2021 Jul 03.

Irisin-Associated Neuroprotective and Rehabilitative Strategies for Stroke.

Melissa Ann Huberman, Nathan D d'Adesky, Qismat Bahar Niazi, Miguel A Perez-Pinzon, Helen M Bramlett, Ami P Raval.

  Irisin, a newly discovered protein hormone that is secreted in response to low frequency whole body vibration (LFV), could be a promising post-stroke rehabilitation therapy for patients who are frail and cannot comply with regular rehabilitation therapy. Irisin is generated from a membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5). Aside from being highly expressed in muscle, FNDC5 is highly expressed in the brain. The cleaved form of FNDC5 was found in the cerebrospinal fluid as well as in various regions of the brain. Numerous studies suggest that irisin plays a key role in brain metabolism and inflammation regulation. Both the metabolism and inflammation govern stroke outcome, and in a published study, we demonstrated that LFV therapy following middle cerebral artery occlusion significantly reduced innate immune response, improved motor function and infarct volume in reproductively senescent female rats. The observed effect of LFV therapy could be working via irisin, therefore, the current review focuses to understand various aspects of irisin including its mechanism of action on the brain.

Keywords:  Fibronectin type III domain-containing protein 5 (FNDC5); Low frequency whole-body vibration (LFV); Menopause; Physical exercise; Stroke

DOI:  https://doi.org/10.1007/s12017-021-08666-y
Biochem Biophys Res Commun. 2021 Jun 29. pii: S0006-291X(21)00865-2. [Epub ahead of print]566 204-210

Endurance exercise improves avoidance learning and spatial memory, through changes in genes of GABA and relaxin-3, in rats.

Mahnaz Sinaei, Hojatollah Alaei, Farzad Nazem, Mehdi Kargarfard, Awat Feizi, Ardeshir Talebi, Abolghasem Esmaeili, Hadi Nobari, Jorge Pérez-Gómez.

  Different exercise patterns, neurotransmitters, and some genes have numerous effects on learning and memory. This research aims to investigate the long-term effects of submaximal aerobic exercise on spatial memory (SM), passive avoidance learning (PAL), levels of serum relaxin-3, gamma-aminobutyric acid (GABA), RLN3 gene, and glutamic acid decarboxylase (GAD65/67 genes) in the brainstem of adult male Wistar rats. Fifty male Wistar rats were randomly divided into five groups: aerobic exercise groups, performed on a treadmill running (TR), for 5 weeks (Ex5, n = 10), 10 weeks (Ex10, n = 10), involuntary running wheel group for 5 weeks (IRW5, n = 10), sham (Sh, n = 10) and control (Co, n = 10). Consequently, SM, PAL, serum relaxin-3, GABA, and GAD65/67 and RLN3 genes were measured by ELISA and PCR. Ex5, Ex10 and IRW5 improved significantly SM (p ≤ 0.05), PAL (p ≤ 0.001) and decreased significantly relaxin-3 (p ≤ 0.001). RLN3 in the brain also decreased. However, it was not significant. GABA and GAD65/GAD67 increased significantly (p ≤ 0.05) in Ex5, Ex10 compared to Sh and Co. Aerobic exercise enhanced SM and PAL in Ex compared to Co and Sh. However, duration and type of exercise affected the level of enhancement. The serum relaxin-3 and RLN3 gene displayed reverse functions compared to GABA and GAD65/67 genes in Ex. Therefore, the changes of neurotransmitters in serum relaxin-3, GABA, and their genes: RLN3 and GAD65/67 respectively, influenced learning and memory meaningfully.

Keywords:  Avoidance learning; Endurance exercise; GABA; GAD65/67; RLN3; Spatial memory

DOI:  https://doi.org/10.1016/j.bbrc.2021.05.080
Appl Psychol Health Well Being. 2021 Jul 01.

Changes in cognitive control and mood across repeated exercise sessions.

Teran Nieman, Maximilian Bergelt, Jessica Clancy, Kayla Regan, Nic Hobson, Alexander Dos Santos, Laura E Middleton.

  Acute exercise elicits benefits to cognition and mood. The consistency and accumulation of benefits across exercise sessions remains unclear. This exploratory study evaluated the reproducibility and accumulation of changes in cognitive control and mood across multiple exercise sessions. Thirty young healthy adults (18-35 years) were recruited to exercise (N = 14; age: 21.71 [SD = 1.64]; 57% female) or control (N = 16; age: 22.25 [SD = 3.68]; 56% female) groups. Participants attended six sessions over 2 weeks (EX = 20-min mod-intensity cycling; CO = 20-min reading). Cognitive control was assessed using a Flanker task (accuracy-adjusted response time, RTLISAS ) pre-/post-intervention. Mood was reported 5×/day on exercise and non-exercise days (pre, post, 11:30 am, 3 pm, and 8 pm) using the Bond-Lader VAS. Cognitive control and mood improved acutely (within session) following exercise compared with control (F(1, 592) = 6.11, p = .0137; F(1, 305.93) = 38.68, p < .0001; F(1, 307.06) = 13.69, p = .0003) and were consistent across sessions. Cognitive control also improved across sessions in both groups (F(5, 282.22) = 11.06, p < .0001). These results suggest that: (1) acute effects of exercise on cognition and mood are consistent across multiple sessions; (2) the Flanker task learning effects continue over many trials/sessions; and (3) accumulated mood effects require further investigation. Future studies should further explore the connection between acute exercise exposures and accumulated cognitive benefits.

Keywords:  affect; cognition; exercise; inhibition; mood

DOI:  https://doi.org/10.1111/aphw.12275