bims-empneu 2021-05-02 papers

bims-empneu

Biomed News

on Exercise and Molecular Pathways Involved in Neuroprotection

Issue of 2021–05–02
nine papers selected by
Navabeh Zare-Kookandeh, Victoria University

Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ.
Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders.
Neurovascular Dysregulation During Exercise in Type 2 Diabetes.
Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults.
Understanding the role of aerobic fitness, spatial learning, and hippocampal subfields in adolescent males.
Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome.
Exercise-Induced MicroRNA Regulation in the Mice Nervous System is Maintained after Activity Cessation.
Neurochemical and Cognitive Beneficial Effects of Moderate Physical Activity and Catechin in Aged Rats.
Effects of a multimodal exercise protocol on functional outcomes, epigenetic modulation and brain-derived neurotrophic factor levels in institutionalized older adults: a quasi-experimental pilot study.

Int J Mol Sci. 2021 Apr 27. pii: 4577. [Epub ahead of print]22(9):

Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ.

Laia Just-Borràs, Víctor Cilleros-Mañé, Erica Hurtado, Olivier Biondi, Frédéric Charbonnier, Marta Tomàs, Neus Garcia, Josep Tomàs, Maria A Lanuza.

  Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes' fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.

Keywords:  BDNF/TrkB signaling; endurance exercise; neuromuscular junction; new activity conditions; skeletal muscle

DOI:  https://doi.org/10.3390/ijms22094577
Int J Mol Sci. 2021 Apr 14. pii: 4052. [Epub ahead of print]22(8):

Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders.

Kévin Nay, William J Smiles, Jacqueline Kaiser, Luke M McAloon, Kim Loh, Sandra Galic, Jonathan S Oakhill, Andrew L Gundlach, John W Scott.

  As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle-brain, liver-brain and gut-brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise-brain communication and their benefits for physiology and brain function.

Keywords:  Alzheimer’s disease; BDNF; Parkinson’s disease; brain; exercise; iron; microbiota

DOI:  https://doi.org/10.3390/ijms22084052
Front Physiol. 2021 ;12 628840

Neurovascular Dysregulation During Exercise in Type 2 Diabetes.

Ann-Katrin Grotle, Jasdeep Kaur, Audrey J Stone, Paul J Fadel.

  Emerging evidence suggests that type 2 diabetes (T2D) may impair the ability to properly adjust the circulation during exercise with augmented blood pressure (BP) and an attenuated contracting skeletal muscle blood flow (BF) response being reported. This review provides a brief overview of the current understanding of these altered exercise responses in T2D and the potential underlying mechanisms, with an emphasis on the sympathetic nervous system and its regulation during exercise. The research presented support augmented sympathetic activation, heightened BP, reduced skeletal muscle BF, and impairment in the ability to attenuate sympathetically mediated vasoconstriction (i.e., functional sympatholysis) as potential drivers of neurovascular dysregulation during exercise in T2D. Furthermore, emerging evidence supporting a contribution of the exercise pressor reflex and central command is discussed along with proposed future directions for studies in this important area of research.

Keywords:  baroreflex; blood flow; blood pressure; central command; exercise pressor reflex; functional sympatholysis; sympathetic nerve activity

DOI:  https://doi.org/10.3389/fphys.2021.628840
Front Aging Neurosci. 2021 ;13 645258

Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults.

Daniel D Callow, Junyeon Won, Gabriel S Pena, Leslie S Jordan, Naomi A Arnold-Nedimala, Yash Kommula, Kristy A Nielson, J Carson Smith.

  Individuals with Mild Cognitive Impairment (MCI) are at an elevated risk of dementia and exhibit deficits in cognition and cortical gray matter (GM) volume, thickness, and microstructure. Meanwhile, exercise training appears to preserve brain function and macrostructure may help delay or prevent the onset of dementia in individuals with MCI. Yet, our understanding of the neurophysiological effects of exercise training in individuals with MCI remains limited. Recent work suggests that the measures of gray matter microstructure using diffusion imaging may be sensitive to early cognitive and neurophysiological changes in the aging brain. Therefore, this study is aimed to determine the effects of exercise training in cognition and cortical gray matter microstructure in individuals with MCI vs. cognitively healthy older adults. Fifteen MCI participants and 17 cognitively intact controls (HC) volunteered for a 12-week supervised walking intervention. Following the intervention, MCI and HC saw improvements in cardiorespiratory fitness, performance on Trial 1 of the Rey Auditory Verbal Learning Test (RAVLT), a measure of verbal memory, and the Controlled Oral Word Association Test (COWAT), a measure of verbal fluency. After controlling for age, a voxel-wise analysis of cortical gray matter diffusivity showed individuals with MCI exhibited greater increases in mean diffusivity (MD) in the left insular cortex than HC. This increase in MD was positively associated with improvements in COWAT performance. Additionally, after controlling for age, the voxel-wise analysis indicated a main effect of Time with both groups experiencing an increase in left insular and left and right cerebellar MD. Increases in left insular diffusivity were similarly found to be positively associated with improvements in COWAT performance in both groups, while increases in cerebellar MD were related to gains in episodic memory performance. These findings suggest that exercise training may be related to improvements in neural circuits that govern verbal fluency performance in older adults through the microstructural remodeling of cortical gray matter. Furthermore, changes in left insular cortex microstructure may be particularly relevant to improvements in verbal fluency among individuals diagnosed with MCI.

Keywords:  MCI; diffusion imaging; episodic memory; exercise training; physical activity; verbal fluency

DOI:  https://doi.org/10.3389/fnagi.2021.645258
Sci Rep. 2021 Apr 29. 11(1): 9311

Understanding the role of aerobic fitness, spatial learning, and hippocampal subfields in adolescent males.

Sandhya Prathap, Bonnie J Nagel, Megan M Herting.

Physical exercise during adolescence, a critical developmental window, can facilitate neurogenesis in the dentate gyrus and astrogliogenesis in Cornu Ammonis (CA) hippocampal subfields of rats, and which have been associated with improved hippocampal dependent memory performance. Recent translational studies in humans also suggest that aerobic fitness is associated with hippocampal volume and better spatial memory during adolescence. However, associations between fitness, hippocampal subfield morphology, and learning capabilities in human adolescents remain largely unknown. Employing a translational study design in 34 adolescent males, we explored the relationship between aerobic fitness, hippocampal subfield volumes, and both spatial and verbal memory. Aerobic fitness, assessed by peak oxygen utilization on a high-intensity exercise test (VO2 peak), was positively associated with the volumetric enlargement of the hippocampal head, and the CA1 head region specifically. Larger CA1 volumes were also associated with spatial learning on a Virtual Morris Water Maze task and verbal learning on the Rey Auditory Verbal Learning Test, but not recall memory. In line with previous animal work, the current findings lend support for the long-axis specialization of the hippocampus in the areas of exercise and learning during adolescence.

DOI: https://doi.org/10.1038/s41598-021-88452-9
Cells. 2021 Apr 17. pii: 938. [Epub ahead of print]10(4):

Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome.

Fabiola Forteza, Giada Giorgini, Frédéric Raymond.

  Evidence suggesting the triangulation of the endocannabinoid system, exercise, and neurological health is emerging. In addition to the endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), the expanded endocannabinoid system, known as the endocannabinoidome (eCBome), appears to be an important player in this relationship. The eCBome includes several endocannabinoid-like mediators such as N-acylethanolamines and 2-monoacylglycerols, the enzymes involved in their biosynthesis and degradation, and the receptors they affect. This review aims to relate the functional interactions between aerobic exercise, and the molecular and cellular pathways related to endocannabinoids, in the hypothalamus, hippocampus, and the periphery, with special attention given to associations with emotional state, cognition, and mental health. Given the well-documented roles of many eCBome members in regulating stress and neurological processes, we posit that the eCBome is an important effector of exercise-induced central and peripheral adaptive mechanisms that benefit mental health. Gut microbiota imbalance, affecting the gut-brain axis and metabolism, also influences certain eCBome-modulated inflammation pathways. The integrity of the gut microbiota could thus be crucial in the onset of neuroinflammation and mental conditions. Further studies on how the modulation by exercise of the peripheral eCBome affects brain functions could reveal to be key elements in the prevention and treatment of neuropsychological disorders.

Keywords:  brain; central nervous system; depression; endocannabinoids; mental health; microbiome; peripheral nervous system; physical activity; stress

DOI:  https://doi.org/10.3390/cells10040938
Microrna. 2021 Apr 25.

Exercise-Induced MicroRNA Regulation in the Mice Nervous System is Maintained after Activity Cessation.

Andrea Carvalho, Sonia Zanon, Guilherme Lucas.

   BACKGROUND: Physical exercise can improve synaptic function and protect the nervous system against many diseases by altering gene regulation. MicroRNAs (miRs) have emerged as vital regulators of gene expression and protein synthesis not only in the muscular system, but also in the brain.
OBJECTIVE: Here we investigated whether exercise-induced miRs expression in the nervous and muscular systems is activity-dependent or it remain regulated even after exercise cessation.
METHODS: The expression profile of miR-1, -16, and -206 was monitored by RT-PCR in the dorsal root ganglion, in the spinal cord dorsal and ventral horn, and in the soleus muscle of mice after 5 weeks of swimming training and after swimming exercise followed by 4 weeks of sedentary conditions. Control animals consisted of mice that swan daily for 30s during the 5-weeks training period, returning to the non-swimming activity for additional 4 weeks.
RESULTS: After exercise, miR-1 was upregulated in all tissues investigated. However, the upregulation of miR-1 continued significantly high in both aspects of the spinal cord, and in the soleus muscle. The expression profiles of miR-16, and -206 were increased only in the nervous system. However, miR-16 upregulation persisted in the DRG and in the spinal cord after exercise interruption, whereas miR-206 continued upregulated only in the spinal cord ventral horn.
CONCLUSION: Exercise training can cause long-lasting changes in the expression of miRs independently of exercise maintenance. Spatial and temporal expression of miRs is to some extent dependent on this activity. The data raised a new conceptual hypothesis on the biogenesis of miRs indicating that long-lasting and systematic exercise can potentially cause irreversible miR regulation after activity cessation.

Keywords:  dorsal root ganglion.; exercise; microRNA; nervous system; physical training; skeletal muscle; spinal cord

DOI:  https://doi.org/10.2174/2211536610666210426101437
Antioxidants (Basel). 2021 Apr 19. pii: 621. [Epub ahead of print]10(4):

Neurochemical and Cognitive Beneficial Effects of Moderate Physical Activity and Catechin in Aged Rats.

Margarita R Ramis, Fiorella Sarubbo, David Moranta, Silvia Tejada, Jerònia Lladó, Antoni Miralles, Susana Esteban.

  A healthy aging process is a requirement for good life quality. A relationship between physical activity, the consumption of antioxidants and brain health has been stablished via the activation of pathways that reduce the harmful effects of oxidative stress, by inducing enzymes such as SIRT1, which is a protector of brain function. We analyzed the cognitive and neurochemical effects of applying physical exercise in elderly rats, alone or in combination with the antioxidant catechin. Several tests of spatial and episodic memory and motor coordination were evaluated. In addition, brain monoaminergic neurotransmitters and SIRT1 protein levels were assessed in the brains of the same rats. The results show that physical activity by itself improved age-related memory and learning deficits, correlating with the restoration of brain monoaminergic neurotransmitters and SIRT1 protein levels in the hippocampus. The administration of the antioxidant catechin along with the exercise program enhanced further the monoaminergic pathways, but not the other parameters studied. These results agree with previous reports revealing a neuroprotective effect of physical activity, probably based on its ability to improve the redox status of the brain, demonstrating that exercise at an advanced age, combined with the consumption of antioxidants, could produce favorable effects in terms of brain health.

Keywords:  5-HT; Dopamine (DA); Noradrenaline (NA); SIRT1; aging; brain health; catechin; memory; monoamines; physical activity

DOI:  https://doi.org/10.3390/antiox10040621
Neural Regen Res. 2021 Dec;16(12): 2479-2485

Effects of a multimodal exercise protocol on functional outcomes, epigenetic modulation and brain-derived neurotrophic factor levels in institutionalized older adults: a quasi-experimental pilot study.

Iasmin Fraga, Camila Weber, Wériton Baldo Galiano, Lucio Iraci, Mariana Wohlgemuth, Gabriela Morales, Camila Cercato, Juliana Rodriguez, Daniela Pochmann, Caroline Dani, Pérsia Menz, Adriane Dal Bosco, Viviane Rostirola Elsner.

  Epigenetic changes have been shown to be associated with both aging process and aging-related diseases. There is evidence regarding the benefits of physical activity on the functionality, cognition, and quality of life of institutionalized older adults, however, the molecular mechanisms involved are not elucidated. The purpose of this pilot study was to investigate the effects of a multimodal exercise intervention on functional outcomes, cognitive performance, quality of life (QOL), epigenetic markers and brain-derived neurotrophic factor (BDNF) levels among institutionalized older adult individuals. Participants (n = 8) without dementia who were aged 73.38 ± 11.28 years and predominantly female (87.5%) were included in this quasi-experimental pilot study. A multimodal exercise protocol (cardiovascular capacity, strength, balance/agility and flexibility, perception and cognition) consisted of twice weekly sessions (60 minutes each) over 8 weeks. Balance (Berg Scale), mobility (Timed Up and Go test), functional capacity (Six-Minute Walk test), cognitive function (Mini-Mental State Examination) and QOL (the World Health Organization Quality of Life-BREF Scale questionnaire) were evaluated before and after the intervention. Blood sample (15 mL) was also collected before and after intervention for analysis of biomarkers global histone H3 acetylation and brain-derived neurotrophic factor levels. Significant improvements were observed in cognitive function, balance, mobility, functional capacity and QOL after the intervention. In addition, a tendency toward an increase in global histone H3 acetylation levels was observed, while brain-derived neurotrophic factor level remained unchanged. This study provided evidence that an 8-week multimodal exercise protocol has a significant effect on ameliorating functional outcomes and QOL in institutionalized older adult individuals. In addition, it was also able to promote cognitive improvement, which seems to be partially related to histone hyperacetylation status. The Ethics Research Committee of Centro Universitário Metodista-IPA, Brazil approved the current study on June 6, 2019 (approval No. 3.376.078).

Keywords:  aging; balance; brain-derived neurotrophic factor; cognition; epigenetics; physical exercise; quality of life; risk of falling

DOI:  https://doi.org/10.4103/1673-5374.313067