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

2021 ◽  
Vol 22 (9) ◽  
pp. 4577
Author(s):  
Laia Just-Borràs ◽  
Víctor Cilleros-Mañé ◽  
Erica Hurtado ◽  
Olivier Biondi ◽  
Frédéric Charbonnier ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Abilities ◽  
Acetylcholine Receptors ◽  
Morphological Changes ◽  
Intermediate Step ◽  
Downstream Signaling ◽  
Molecular Pattern ◽  
Functional Transition ◽  
Synapse Maintenance ◽  
Therapeutic Tools

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.

scholarly journals Association of beta-cytoplasmic actin with high concentrations of acetylcholine receptor (AChR) in normal and anti-AChR-treated primary rat muscle cultures.

1984 ◽  
Vol 32 (9) ◽  
pp. 973-981 ◽  
Author(s):  
B W Lubit
Keyword(s):  
Acetylcholine Receptor ◽  
Acetylcholine Receptors ◽  
Neuromuscular Junctions ◽  
Morphological Changes ◽  
Muscle Cells ◽  
High Concentration ◽  
Rat Muscle ◽  
Cytoplasmic Actin ◽  
High Concentrations

Previous immunocytochemical studies in which an antibody specific for mammalian cytoplasmic actin was used showed that a high concentration of cytoplasmic actin exists at neuromuscular junctions of rat muscle fibers such that the distribution of actin corresponded exactly to that of the acetylcholine receptors. Although clusters of acetylcholine receptors also are present in noninnervated rat and chick muscle cells grown in vitro, neither the mechanism for the formation and maintenance of these clusters nor the relationship of these clusters to the high density of acetylcholine receptors at the neuromuscular junction in vivo are known. In the present study, a relationship between beta-cytoplasmic actin and acetylcholine receptors in vitro has been demonstrated immunocytochemically using an antibody specific for the beta-form of cytoplasmic actin. Networks of cytoplasmic actin-containing filaments were found in discrete regions of the myotube membrane that also contained high concentrations of acetylcholine receptors; such high concentrations of acetylcholine receptors have been described in regions of membrane-substrate contact. Moreover, when primary rat myotubes were exposed to human myasthenic serum, gross morphological changes, accompanied by an apparent rearrangement of the cytoplasmic actin-containing cytoskeleton, were produced. Although whether the distribution of cytoplasmic actin-containing structures was influenced by the organization of acetylcholine receptor or vice versa cannot be determined from these studies, these findings suggest that in primary rat muscle cells grown in vitro, acetylcholine receptors and beta-cytoplasmic actin-containing structures may be somehow connected.

Keep Your Brain Tissue Healthy

2021 ◽  
pp. 27-66
Author(s):  
Charles Alessi ◽  
Larry W. Chambers ◽  
Muir Gray
Keyword(s):  
Physical Activity ◽  
Immune System ◽  
Inflammatory Response ◽  
Stress Reduction ◽  
Indirect Effects ◽  
Cognitive Abilities ◽  
Direct And Indirect Effects ◽  
The Impact ◽  
The Brain

This chapter starts by advising how to reduce the impact of stress. When stress becomes long term, the immune system becomes less sensitive to cortisol, and since inflammation is partly regulated by this hormone, this decreased sensitivity heightens the inflammatory response and allows inflammation to get out of control, increasing our risk of many diseases. You can reduce your stress yourself through a variety of methods, including physical activity and mindfulness-based stress reduction. Adequate sleep is also a major factor that can improve cognitive abilities and reduce the risk of dementia, and this chapter outlines what we need to know about sleep cycles, insomnia, and sleep disordered breathing, and how to sleep more and sleep better. The chapter then covers how to protect your brain from over medication (polypharmacy). It finishes by discussing how to maintain and indeed increase your levels of physical activity, and how increasing physical activity has both direct and indirect effects on the brain.

scholarly journals Participation in Organized Sports and Self-Organized Physical Activity: Associations with Developmental Factors

2019 ◽  
Vol 16 (4) ◽  
pp. 585 ◽  
Author(s):  
Nora Wiium ◽  
Reidar Säfvenbom
Keyword(s):  
Physical Activity ◽  
Cognitive Abilities ◽  
Self Regulation ◽  
Well Being ◽  
Free Play ◽  
Organized Activities ◽  
Organized Sports ◽  
Developmental Factors ◽  
Self Organized ◽  
Healthy Growth

Engagement in organized sports is associated with developmental factors, such as, healthy growth, cognitive abilities, psychological well-being and lower substance use. Research also suggest that the spontaneous free play that characterises self-organized physical activity (PA) provides young people with opportunities to learn social skills, such as self-regulation and conflict-resolution skills. We assessed associations between participation in the two activity types and several demographics along with developmental factors (e.g., body mass index (BMI)). Data was from a representative sample of 2060 students attending 38 schools in Norway (mean age (Mage) = 15.29, standard deviation (SD) = 1.51; 52% females). Results indicated that while engagement in organized sports was more related to developmental factors, relative to self-organized PA, engaging concurrently in both activities for at least an hour a week was more developmentally beneficial than engaging only in one for the same amount of time. Thus, PA programmes for students will enhance their effectiveness if they focus on structured activities but also self-organized activities where students can coordinate themselves.

scholarly journals A daily process analysis of physical activity, sedentary behavior, and perceived cognitive abilities

2014 ◽  
Vol 15 (5) ◽  
pp. 498-504 ◽  
Author(s):  
Patrick T. Fitzsimmons ◽  
Jaclyn P. Maher ◽  
Shawna E. Doerksen ◽  
Steriani Elavsky ◽  
Amanda L. Rebar ◽  
...  
Keyword(s):  
Physical Activity ◽  
Sedentary Behavior ◽  
Cognitive Abilities ◽  
Process Analysis ◽  
Daily Process

scholarly journals p53-Dependent DNA damage response sensitive to editing-defective tRNA synthetase in zebrafish

2016 ◽  
Vol 113 (30) ◽  
pp. 8460-8465 ◽  
Author(s):  
Youngzee Song ◽  
Yi Shi ◽  
Tristan M. Carland ◽  
Shanshan Lian ◽  
Tomoyuki Sasaki ◽  
...  
Keyword(s):  
Dna Damage ◽  
Life Span ◽  
Morphological Changes ◽  
Critical Role ◽  
Trna Synthetase ◽  
Trna Synthetases ◽  
Downstream Signaling ◽  
Cycle Arrest ◽  
Normal Life Span ◽  
Transient Overexpression

Brain and heart pathologies are caused by editing defects of transfer RNA (tRNA) synthetases, which preserve genetic code fidelity by removing incorrect amino acids misattached to tRNAs. To extend understanding of the broader impact of synthetase editing reactions on organismal homeostasis, and based on effects in bacteria ostensibly from small amounts of mistranslation of components of the replication apparatus, we investigated the sensitivity to editing of the vertebrate genome. We show here that in zebrafish embryos, transient overexpression of editing-defective valyl-tRNA synthetase (ValRSED) activated DNA break-responsive H2AX and p53-responsive downstream proteins, such as cyclin-dependent kinase (CDK) inhibitor p21, which promotes cell-cycle arrest at DNA damage checkpoints, and Gadd45 and p53R2, with pivotal roles in DNA repair. In contrast, the response of these proteins to expression of ValRSED was abolished in p53-deficient fish. The p53-activated downstream signaling events correlated with suppression of abnormal morphological changes caused by the editing defect and, in adults, reversed a shortened life span (followed for 2 y). Conversely, with normal editing activities, p53-deficient fish have a normal life span and few morphological changes. Whole-fish deep sequencing showed genomic mutations associated with the editing defect. We suggest that the sensitivity of p53 to expression of an editing-defective tRNA synthetase has a critical role in promoting genome integrity and organismal homeostasis.

Sport als Prävention von Demenz und ­funktionellem Verlust im Alter

2014 ◽  
Vol 62 (4) ◽  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Cognitive Abilities ◽  
Lifestyle Changes ◽  
Cognitive Domains ◽  
Dementia Prevalence ◽  
Positive Effects ◽  
Preventative Measures ◽  
Wide Range ◽  
Study Designs

As a consequence of the demographically related increase of dementia prevalence, modifiable risk factors are gaining in importance as possible preventative measures. Medical treatment cannot yet heal dementia. The effects of vascular risk factors as well as behaviour and lifestyle changes on cognitive decline are the subject of a wide range of current literature. The role of physical activity has proved to be especially beneficial. Multiple studies with different study designs describe direct or indirect positive effects of physical activity on cognitive abilities. The positive effects of physical activity are particularly notable in cognitive domains such as attention or executive functions, which are often impaired in dementia. However, ideal training sessions in terms of type, duration and intensity are currently unknown.

Abstract P245: Activation Of Protease-activated Receptors 1 Leads To Structural Changes In Immortalized Cultured Human Podocytes.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ruslan Bohovyk ◽  
Sherif Khedr ◽  
Christine A Klemens ◽  
Vladislav Levchenko ◽  
Olena Isaeva ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Structural Changes ◽  
Calcium Influx ◽  
Morphological Changes ◽  
Confocal Imaging ◽  
Protease Activated Receptors ◽  
Ion Conductance ◽  
Downstream Signaling ◽  
Filtration Barrier ◽  
Intracellular Ca

Previous studies have suggested that activation of the protease-activated receptors (PAR) exacerbates the development of diabetic nephropathy. PARs are transmembrane proteins activated by extracellular serine proteases, such as thrombin and trypsin, which are frequently elevated in disease states. We hypothesize that serine protease activation of the PAR1 signaling cascade upregulates calcium channel activity and promotes excessive intracellular Ca 2+ ([Ca 2+ ] i ), leading to podocyte foot retraction, apoptosis, and glomerular filtration barrier (GFB) damage. Immunofluorescent labeling revealed the co-localization of PAR1 and podocyte marker nephrin in freshly isolated human glomeruli. To explore the functional role of PAR1 mediated signaling, we used an immortalized cultured human podocyte (hPod) cell line. Live confocal imaging revealed rapid elevation of [Ca 2+ ] i in response to a PAR1 specific agonist (TFLLR-NH 2 ). Moreover, preincubation with a PAR1 antagonist (RWJ 56100) completely blocked this effect (1616±48 vs. 206±135 a.u., for TFLLR vs. TFLLR+RJW, n<100 cells, p<0.05). Furthermore, we tested potential downstream signaling proteins in hPod cells after PAR1 activation using Western blot analysis. Application of TFLLR-NH 2 led to a decrease in PAR1 expression due to internalization and lysosomal degradation, accompanied by an increase in TRPC6 expression and time-dependent changes in p-ERK1/2 and PLC-γ1 cascades. We further used scanning ion-conductance microscopy (SICM) to detect morphological changes in podocytes, which measures real-time surface topography in hPod cells. This imaging revealed normal protrusion of lamellipodium under control conditions. In contrast, PAR1 activation led to retraction of the lamellipodium, and a significant decrease in surface area (+51±46 vs. -15±8 μm 2 , 30 min after application of vehicle or TFLLR, respectively; n=5, p<0.05). Our studies suggested that PAR1 is involved in GPCR-induced calcium influx in podocytes. Furthermore, these data demonstrate that PAR1-mediated signaling is involved in podocyte structural alterations and may increase [Ca 2+ ] i , potentially leading to loss of GFB integrity and podocyte apoptosis.

A Novel Effect of PDLIM5 In α7 Nicotinic Acetylcholine Receptors Up-Regulation And Surface Expression

2021 ◽  
Author(s):  
Zilin Li ◽  
Chenyu Gou ◽  
Wenhui Wang ◽  
Yuan Li ◽  
Yu Cui ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Hippocampal Neurons ◽  
Acetylcholine Receptors ◽  
Pdz Domain ◽  
Surface Expression ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Downstream Signaling ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Cultured Hippocampal Neurons

Abstract α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are expressed widely in the brain, where they contribute to a variety of behaviors including arousal and cognition, participate in a number of neurodegenerative disorders including Alzheimer’s and Parkinson’s disease, and is responsible for nicotine addiction. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated are still less well understood. Here we show that the regulation of the α7nAChRs is controlled by PDLIM5 in the endogenous PDZ domain proteins family. We find that chronic exposure to 1 μM nicotine up-regulated both α7, β2-contained nAChRs and PDLIM5 in primary cultured hippocampal neurons, and the up-regulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, the α7nAChRs and β2nAChRs display distinct patterns of expression, with α7 co-localized more with PDLIM5. Meanwhile, PDLIM5 interacts with native brain α7 but not β2 nAChRs in neurons. Moreover, knocking down of PDLIM5 in heterologous cells abolishes nicotine-induced up-regulation of α7nAChRs. In cultured hippocampal neurons, shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs mediated currents. Proteomics analysis shows PDLIM5 interacts with α7nAChRs through the PDZ domain and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in regulating α7nAChRs, which may be relevant to plastic changes in the nervous system.

scholarly journals Physical Activity, Exercise and Sport Programs as Effective Therapeutic Tools in Psychosocial Rehabilitation

2018 ◽  
Vol 14 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Federica Sancassiani ◽  
Sergio Machado ◽  
Antonio Preti
Keyword(s):  
Physical Activity ◽  
Mental Health Professionals ◽  
Multidisciplinary Teams ◽  
Psychosocial Needs ◽  
Secondary Effects ◽  
Somatic Comorbidities ◽  
Therapeutic Tools ◽  
The Impact

People with severe psychosocial disabilities have a 20-years shorter lifespan due to chronic somatic comorbidities and the long-term consequences of the side-effects of antipsychotic drugs.They often are sedentary and show lower levels of physical activity, factors which can contribute to their shorter lifespan, because of the greater cardiovascular risk.An increasing amount of evidence, including clinical trials, pointed out that sport, physical activity and structured exercise programs improve physical and psychological wellbeing of people with psychosocial disabilities, playing also an important role against their social isolation and self-stigma.The NICE and APA guidelines include exercise and physical activity for the management of depressive symptoms.Safe and effective programs require multidisciplinary teams that should always include mental health professionals, able to recognize the psychosocial needs, the impact of symptomatology, the role of secondary effects of psychotropic medication, the effect of previous exercise history, the lack of motivation, the inexperience with effort intensity and the frustration of people with psychosocial disabilities.

scholarly journals Integrin Signaling in Glioma Pathogenesis: From Biology to Therapy

2020 ◽  
Vol 21 (3) ◽  
pp. 888 ◽  
Author(s):  
Aleksandra Ellert-Miklaszewska ◽  
Katarzyna Poleszak ◽  
Maria Pasierbinska ◽  
Bozena Kaminska
Keyword(s):  
Morphological Changes ◽  
Large Family ◽  
Integrin Signaling ◽  
Downstream Signaling ◽  
Receptor Complexes ◽  
Attractive Therapeutic Target ◽  
A Cell ◽  
Covalently Linked ◽  
Phosphoinositide 3 Kinase ◽  
Integrin Ligand

Integrins are a large family of transmembrane adhesion receptors, which play a key role in interactions of a cell with the surrounding stroma. Integrins are comprised of non-covalently linked α and β chains, which form heterodimeric receptor complexes. The signals from integrin receptors are combined with those originating from growth factor receptors and participate in orchestrating morphological changes of cells, organization of the cytoskeleton, stimulation of cell proliferation and rescuing cells from programmed cell death induced by extracellular matrix (ECM) detachment. Upon binding to specific ligands or ECM components, integrin dimers activate downstream signaling pathways, including focal adhesion kinase, phosphoinositide-3-kinase (PI3K) and AKT kinases, which regulate migration, invasion, proliferation and survival. Expression of specific integrins is upregulated in both tumor cells and stromal cells in a tumor microenvironment. Therefore, integrins became an attractive therapeutic target for many cancers, including the most common primary brain tumors—gliomas. In this review we provide an overview of the involvement of integrin signaling in glioma pathogenesis, formation of the tumor niche and brain tissue infiltration. We will summarize up-to-date therapeutic strategies for gliomas focused on interference with integrin ligand-receptor signaling.

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