1,721,181 research outputs found
MITOCHONDRIAL MEMORY AT SKELETAL MUSCLE LEVEL
Full text linkMitochondria are key components of skeletal muscles as they provide the energy required for almost all cellular activities. Different forms of exercise training have been associated with mitochondrial adaptations, such as increased mitochondrial content and function, and enhanced mitochondrial biogenesis, as well as improved endurance performance. High-intensity interval training and sprint interval training have been demonstrated to be the most effective training modalities to induce mitochondrial adaptations. However, surprisingly, greater changes in mitochondrial content and biogenesis were also observed after repeated resistance training interventions separated by prolonged detraining. This mechanism, defined muscle memory, has been well established for hypertrophy and skeletal muscle growth in response to resistance training and it has been related to the retention of acquired myonuclei or epigenetic modifications. Thereby, even mitochondrial adaptations might be influenced by muscle memory, but it remains to be explored whether repeated endurance training interventions can rely on the same mechanism. Therefore, the overarching aim of the present thesis was to investigate the potential presence of mitochondrial memory in response to repeated high- intensity endurance training interventions. An experimental design composed of two periods of 8 weeks of interval training interspersed by 3 months of detraining was conducted on murine model and humans. In mice, maximal running velocity (Vmax) by graded exercise test (GXT) on a rodent treadmill. In addition, biomarkers of mitochondrial biogenesis and content, and fusion-fission mitochondrial key factors were analyzed on gastrocnemius muscle by western Blot. Results revealed that endurance performance improved to a greater extent after retraining than training. This functional adaptation was supported by a larger mitochondrial content resulting from a more pronounced mitochondrial biogenesis response after retraining. Mitochondrial dynamics were shifted mainly towards fusion, suggesting larger and more elongated mitochondria and finally, the retraining period elicited increased mitophagic flux, which, associated with a smaller increment in the amount of respiratory chain complexes, suggests an improvement in clearance of damaged mitochondria in order to ensure healthier mitochondria and more efficient respiratory function. In humans, maximal aerobic capacity and peak power output were measured and muscle sample from vastus lateralis was used for mitochondrial respiration and epigenetic analysis. Mitochondrial function resulted in a greater improvement after high intensity aerobic stimulus when previous exposure to an identical stimulus has been occurred separated by long-term period of stimulus cessation. The underlying mechanism could reside in epigenetic modifications induced by interval training which led to DNA hypomethylation. Two memory profiles were highlighted at epigenetic level characterized by retention of hypomethylation even during the prolonged detraining period and involving differentially methylated regions related with genes implicated in skeletal muscle metabolic pathways. Overall, these studies provided evidence for a skeletal muscle memory mechanism, specifically at mitochondrial level, elicited by high-intensity aerobic training that affects muscle aerobic phenotype initiating at the epigenetic level and extends upstream to affect mitochondrial function and endurance performance
Developments in the Role of Transcranial Sonography for the Differential Diagnosis of Parkinsonism
No full textPharmacological strategies for the management of levodopa-induced dyskinesia in patients with parkinson's disease
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Microarray gene and miRNA expression studies: Looking for new therapeutic targets for frontotemporal lobar degeneration
No full textReply to the Letter “COVID‐19‐Associated Encephalopathy and Cytokine‐Mediated Neuroinflammation”
No full textGender-Related Vulnerability of Dopaminergic Neural Networks in Parkinson's Disease
No full textBackground:
In Parkinson's disease (PD), neurodegeneration of dopaminergic systems leads to motor and non-motor abnormalities. Sex might influence the clinical PD phenotypes and progression. Previous molecular imaging data focused only on the nigro-striato-cortical dopamine system that appeared more preserved in women. There is still a lack of evidence on gender/sex differences in the mesolimbic dopaminergic system. We aimed at assessing PD gender differences in both the dopaminergic pathways, by using a brain metabolic connectivity approach. This is based on the evidence of a significant coupling between the neurotransmission and metabolic impairments.
Methods:
We included 34 idiopathic PD patients (Female/Male: 16/18) and 34 healthy controls for comparison. The molecular architecture of both the dopaminergic networks was estimated throughout partial correlation analyses using brain metabolism data obtained by fluorine-18-fluorodeoxyglucose positron emission tomography (threshold set at p < 0.01, corrected for Bonferroni multiple comparisons).
Results:
Male patients were characterized by a widespread altered connectivity in the nigro-striato-cortical network and a sparing of the mesolimbic pathway. On the contrary, PD females showed a severe altered connectivity in the mesolimbic network and only a partial reconfiguration of the nigro-striato-cortical network.
Discussion:
Our findings add remarkable knowledge on the neurobiology of gender differences in PD, with the identification of specific neural vulnerabilities. The gender differences here revealed might be due to the combination of both biological and sociodemographic life factors. Gender differences in PD should be considered also for treatments and the targeting of modifiable risk factors
Disease-modifying therapies in frontotemporal lobar degeneration.
No full textFrontotemporal Lobar Degeneration (FTLD) is characterized by behavioral changes, executive dysfunctions, and language impairment, sustained by different neuropathological patterns. The collective efforts of clinical, pathological and genetic studies have recently opened new insights into the underpinnings of pathological mechanisms of this complex disorder. Different types of inclusions define the new conceptual framework for FTLD classification. Up to now, Tau (FTLDTau-positive), TAR DNA-binding protein (TDP43, FTLD Tau-negative TDP43-positive) have been recognized as the most frequent neuropathological hallmarks of FTLD. In some clinical cases, monogenic forms are identified, mainly due to Microtubule Associated Protein (MAPT) or Granulin (GRN) mutations. No treatments for FTLD are available yet, and off-label medications studies testing potential modifying treatments on the basis of neuropathological positive, inhibitors of Tau kinases or manipulation of Tau-processing haploinsuffciency associated with GRN mutations, has been counteracted into pathological processing of TDP-43 and other key-molecules involved and their consequent translocation from nucleus to cytoplasm, and growing number of potential therapeutic targets. In this continuously new findings on molecular targets and modifying therapies in FTL
NIRS-Based Muscle Oxygenation Is Not Suitable to Compute Convective and Diffusive Components of O2 Transport at V̇O2max
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