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Le sport pour prévenir la maladie d'Alzheimer

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Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Conseils » 7 Avr 2021 11:41

Brain Ischemia as a Prelude to Alzheimer's Disease
Front. Aging Neurosci., 18 February 2021 | Ryszard Pluta

Transient ischemic brain injury causes massive neuronal death in the hippocampus of both humans and animals. This was accompanied by progressive atrophy of the hippocampus, brain cortex, and white matter lesions. Furthermore, it has been noted that neurodegenerative processes after an episode of ischemia-reperfusion in the brain can continue well-beyond the acute stage. Rarefaction of white matter was significantly increased in animals at 2 years following ischemia. Some rats that survived 2 years after ischemia developed severe brain atrophy with dementia. The profile of post-ischemic brain neurodegeneration shares a commonality with neurodegeneration in Alzheimer's disease. Furthermore, post-ischemic brain injury is associated with the deposition of folding proteins, such as amyloid and tau protein, in the intracellular and extracellular space. Recent studies on post-ischemic brain neurodegeneration have revealed the dysregulation of Alzheimer's disease-associated genes such as amyloid protein precursor, α-secretase, β-secretase, presenilin 1, presenilin 2, and tau protein. The latest data demonstrate that Alzheimer's disease-related proteins and their genes play a key role in the development of post-ischemic brain neurodegeneration with full-blown dementia in disease types such as Alzheimer's.

Ongoing interest in the study of brain ischemia has provided evidence showing that ischemia may be involved in the development of the genotype and phenotype of Alzheimer's disease, suggesting that brain ischemia can be considered as a useful model for understanding the mechanisms responsible for the initiation of Alzheimer's disease.
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Re: Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Conseils » 7 Avr 2021 11:44

Exercise boosts blood flow to the brain, study finds
The results add to growing evidence that exercise programs may help older adults slow the onset of memory loss and dementia


DALLAS – March 23, 2021 – It’s not just your legs and heart that get a workout when you walk briskly; exercise affects your brain as well. A new study by researchers at UT Southwestern shows that when older adults with mild memory loss followed an exercise program for a year, the blood flow to their brains increased. The results were published online today in the Journal of Alzheimer’s Disease.

“This is part of a growing body of evidence linking exercise with brain health,” says study leader Rong Zhang, Ph.D., professor of neurology at UTSW. “We’ve shown for the first time in a randomized trial in these older adults that exercise gets more blood flowing to your brain.”

As many as one-fifth of people age 65 and older have some level of mild cognitive impairment (MCI) – slight changes to the brain that affect memory, decision-making, or reasoning skills. In many cases, MCI progresses to dementia, including Alzheimer’s disease.

Scientists have previously shown that lower-than-usual levels of blood flow to the brain, and stiffer blood vessels leading to the brain, are associated with MCI and dementia. Studies have also suggested that regular aerobic exercise may help improve cognition and memory in healthy older adults. However, scientists have not established whether there is a direct link between exercise, stiffer blood vessels, and brain blood flow.

“There is still a lot we don’t know about the effects of exercise on cognitive decline later in life,” says C. Munro Cullum, Ph.D., professor of psychiatry at UTSW and co-senior author of the study. “MCI and dementia are likely to be influenced by a complex interplay of many factors, and we think that, at least for some people, exercise is one of those factors.”

In the study, Zhang, Cullum, and their colleagues followed 70 men and women aged 55 to 80 who had been diagnosed with MCI. Participants underwent cognitive exams, fitness tests, and brain magnetic resonance imaging (MRI) scans. Then they were randomly assigned to either follow a moderate aerobic exercise program or a stretching program for one year. The exercise program involved three to five exercise sessions a week, each with 30-40 minutes of moderate exercise such as a brisk walk.

In both programs, exercise physiologists supervised participants for the first four to six weeks, then had the patients record their exercises and wear a heart rate monitor during exercise.

Forty-eight study participants – 29 in the stretching group and 19 in the aerobic exercise group – completed the full year of training and returned for follow-up tests. Among them, those who performed aerobic exercise showed decreased stiffness of blood vessels in their neck and increased overall blood flow to the brain. The more their oxygen consumption (one marker of aerobic fitness) increased, the greater the changes to the blood vessel stiffness and brain blood flow. Changes in these measurements were not found among people who followed the stretching program.

While the study didn’t find any significant changes in memory or other cognitive function, the researchers say that may be because of the small size or short length of the trial. Changes to blood flow could precede changes to cognition, they say. They’re already carrying out a larger two-year study, Risk Reduction for Alzheimer’s Disease (rrAD), that further investigates the link between exercise and cognitive decline.

“There are likely some people who benefit more from exercise than others,” says Cullum. “But with the sample size in this study, it was hard to analyze subgroups of people to make those conclusions.”

Still, the data are important to help explain the effects of exercise on the brain and why it can be beneficial, say Zhang and Cullum, who are members of the Peter O’Donnell Jr. Brain Institute.

“Having physiological findings like this can also be useful for physicians when they talk to their patients about the benefits of exercise,” says Zhang. “We now know, based on a randomized, controlled trial, that exercise can increase blood flow to the brain, which is a good thing.”
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Re: Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Conseils » 7 Avr 2021 11:45

One-Year Aerobic Exercise Reduced Carotid Arterial Stiffness and Increased Cerebral Blood Flow in Amnestic Mild Cognitive Impairment
Tomoto, Tsubasaa Journal of Alzheimer’s Disease. 2021


Abstract: Background:Central arterial stiffness and brain hypoperfusion are emerging risk factors of Alzheimer’s disease (AD). Aerobic exercise training (AET) may improve central arterial stiffness and brain perfusion. Objective:To investigate the effects of AET on central arterial stiffness and cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods:This is a proof-of-concept, randomized controlled trial that assigned 70 amnestic MCI patients into a 12-month program of moderate-to-vigorous AET or stretching-and-toning (SAT) intervention. Carotid β-stiffness index and CBF were measured by color-coded duplex ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass assessed with MRI to obtain normalized CBF (nCBF). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Changes in cardiorespiratory fitness were measured by peak oxygen uptake (VO2peak). Results:Total 48 patients (29 in SAT and 19 in AET) were completed one-year training. AET improved VO2peak, decreased carotid β-stiffness index and CBF pulsatility, and increased nCBF. Changes in VO2peak were associated positively with changes in nCBF (r = 0.388, p = 0.034) and negatively with carotid β-stiffness index (r = –0.418, p = 0.007) and CBF pulsatility (r = –0.400, p = 0.014). Decreases in carotid β-stiffness were associated with increases in cerebral perfusion (r = –0.494, p = 0.003). AET effects on cognitive performance were minimal compared with SAT.

Conclusion:AET reduced central arterial stiffness and increased CBF which may precede its effects on neurocognitive function in patients with MCI.
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Re: Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Conseils » 7 Avr 2021 11:53

Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer’s Disease and Type 2 Diabetes
Manel Ben Aissa ACS Pharmacol. Transl. Sci. 2021, 4, 1, 143–154

Selective liver X receptor (LXR) agonists have been extensively pursued as therapeutics for Alzheimer’s disease and related dementia (ADRD) and, for comorbidities such as type 2 diabetes (T2D) and cerebrovascular disease (CVD), disorders with underlying impaired insulin signaling, glucose metabolism, and cholesterol mobilization. The failure of the LXR-focused approach led us to pursue a novel strategy to discover nonlipogenic ATP-binding cassette transporter A1 (ABCA1) inducers (NLAIs): screening for ABCA1-luciferase activation in astrocytoma cells and counterscreening against lipogenic gene upregulation in hepatocarcinoma cells. Beneficial effects of LXRβ agonists mediated by ABCA1 include the following: control of cholesterol and phospholipid efflux to lipid-poor apolipoproteins forming beneficial peripheral HDL and HDL-like particles in the brain and attenuation of inflammation. While rare, ABCA1 variants reduce plasma HDL and correlate with an increased risk of ADRD and CVD. In secondary assays, NLAI hits enhanced cholesterol mobilization and positively impacted in vitro biomarkers associated with insulin signaling, inflammatory response, and biogenic properties. In vivo target engagement was demonstrated after oral administration of NLAIs in (i) mice fed a high-fat diet, a model for obesity-linked T2D, (ii) mice administered LPS, and (iii) mice with accelerated oxidative stress. The lack of adverse effects on lipogenesis and positive effects on multiple biomarkers associated with T2D and ADRD supports this novel phenotypic approach to NLAIs as a platform for T2D and ADRD drug discovery.
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Re: Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Diététique » 7 Avr 2021 16:19

Traduction de l'étude :wink:

Découverte de composés inducteurs d’ABCA1 non lipogènes ayant un potentiel dans la maladie d’Alzheimer et le diabète de type 2
Manel Ben Aissa ACS Pharmacol. Transl. Sci. 2021, 4, 1, 143–154

Les agonistes sélectifs des récepteurs hépatiques X (LXR) ont été largement étudiés comme agents thérapeutiques pour la maladie d'Alzheimer et la démence associée (ADRD) et, pour les comorbidités telles que le diabète de type 2 (DT2) et les maladies cérébrovasculaires (MCV), les troubles sous-jacents à la signalisation insulinique altérée, le glucose métabolisme et mobilisation du cholestérol. L'échec de l'approche centrée sur le LXR nous a conduit à poursuivre une nouvelle stratégie pour découvrir des inducteurs du transporteur A1 (ABCA1) de cassette de liaison à l'ATP non lipogène (NLAI): dépistage de l'activation de l'ABCA1-luciférase dans les cellules d'astrocytome et contre-dépistage contre la régulation à la hausse du gène lipogène dans les cellules d'hépatocarcinome . Les effets bénéfiques des agonistes de la LXRβ médiés par ABCA1 sont les suivants: contrôle de l'efflux de cholestérol et de phospholipides vers les apolipoprotéines pauvres en lipides formant des particules périphériques bénéfiques de type HDL et HDL dans le cerveau et atténuation de l'inflammation. Bien que rares, les variants d'ABCA1 réduisent le HDL plasmatique et sont en corrélation avec un risque accru d'ADRD et de MCV. Dans les tests secondaires, le NLAI atteint une mobilisation accrue du cholestérol et a un impact positif sur les biomarqueurs in vitro associés à la signalisation de l'insuline, à la réponse inflammatoire et aux propriétés biogéniques. L'engagement de la cible in vivo a été démontré après l'administration orale de NLAI chez (i) des souris nourries avec un régime riche en graisses, un modèle de DT2 lié à l'obésité, (ii) des souris ayant reçu du LPS et (iii) des souris avec un stress oxydatif accéléré. L'absence d'effets indésirables sur la lipogenèse et d'effets positifs sur plusieurs biomarqueurs associés au T2D et ADRD soutient cette nouvelle approche phénotypique des NLAI en tant que plate-forme pour la découverte de médicaments T2D et ADRD.
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Re: Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Conseils » 24 Fév 2022 10:56

Post-Exercise Serum from Humans Influences the Biological Tug of War of APP Processing in Human Neuronal Cells
Daniel M. Marko Am J Physiol 23 FEB 2022

Neurodegenerative diseases such as Alzheimer's disease (AD) are becoming more prevalent in our aging society. One specific neuropathological hallmark of this disease is the accumulation of amyloid-β (Aβ) peptides, which aggregate to form extra-neuronal plaques. Increased Aβ peptides are often observed well before symptoms of AD develop, highlighting the importance of targeting Aβ producing pathways early on in disease progression.

Evidence indicates that exercise has the capacity to reduce Aβ peptide production in the brain however the mechanisms remain unknown. Exercise-induced signaling mediators could be the driving force behind some of the beneficial effects observed in the brain with exercise. The purpose of this study was to examine if post-exercise serum and the factors it contains can alter neuronal APP processing. Human SH-SY5Y neuronal cells were differentiated with retinoic acid for 5 days and treated with 10% pre- or post-exercise serum from humans for 30 minutes. Cells were collected for analysis of acute (30 minutes; n=6) or adaptive (24 hours post-treatment; n=6) responses. There were no statistical differences in ADAM10 and BACE1 mRNA or protein expression with post-exercise serum treatment at either time point.

However, there was an increase in the ratio of sAPPa to sAPPβ protein content (p=0.05) after 30 minutes of post-exercise serum treatment. Additionally, 30 minutes of post-exercise serum treatment increased ADAM10 (p=0.01) and BACE1 (p=0.02) activity.

These findings suggest that post-exercise serum modulates important enzymes involved in APP processing, pushing the cascade towards the non-amyloidogenic arm.
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Re: Le sport pour prévenir la maladie d'Alzheimer

Messagepar Nutrimuscle-Diététique » 24 Fév 2022 18:48

Traduction de l'étude :wink:

Le sérum post-exercice des humains influence le bras de fer biologique du traitement de l'APP dans les cellules neuronales humaines
Daniel M. Marko Suis J Physiol 23 FÉV 2022

Les maladies neurodégénératives telles que la maladie d'Alzheimer (MA) sont de plus en plus répandues dans notre société vieillissante. Une caractéristique neuropathologique spécifique de cette maladie est l'accumulation de peptides amyloïdes-β (Aβ), qui s'agrègent pour former des plaques extra-neuronales. Une augmentation des peptides Aβ est souvent observée bien avant que les symptômes de la MA ne se développent, ce qui souligne l'importance de cibler les voies productrices d'Aβ dès le début de la progression de la maladie.

Les preuves indiquent que l'exercice a la capacité de réduire la production de peptide Aβ dans le cerveau, mais les mécanismes restent inconnus
. Les médiateurs de signalisation induits par l'exercice pourraient être la force motrice derrière certains des effets bénéfiques observés dans le cerveau avec l'exercice. Le but de cette étude était d'examiner si le sérum post-exercice et les facteurs qu'il contient peuvent altérer le traitement neuronal de l'APP. Des cellules neuronales humaines SH-SY5Y ont été différenciées avec de l'acide rétinoïque pendant 5 jours et traitées avec 10 % de sérum humain pré- ou post-exercice pendant 30 minutes. Les cellules ont été collectées pour l'analyse des réponses aiguës (30 minutes ; n = 6) ou adaptatives (24 heures après le traitement ; n = 6). Il n'y avait aucune différence statistique dans l'expression de l'ARNm ou de la protéine ADAM10 et BACE1 avec le traitement sérique post-exercice à l'un ou l'autre moment.

Cependant, il y a eu une augmentation du rapport entre la teneur en protéines sAPPa et sAPPβ (p = 0, 05) après 30 minutes de traitement sérique post-exercice. De plus, 30 minutes de traitement sérique post-exercice ont augmenté l'activité ADAM10 (p = 0,01) et BACE1 (p = 0,02).

Ces résultats suggèrent que le sérum post-exercice module des enzymes importantes impliquées dans le traitement de l'APP, poussant la cascade vers le bras non amyloïdogène.
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