Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy.

Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy. Behav Brain Res. 2019 Jun 22;:112007 Authors: Xu B, Zhu L, Chu J, Ma Z, Fu Q, Wei W, Deng X, Ma S Abstract Mitochondrial dynamics regulate mitochondrial autophagy (mitophagy) and apoptosis, which are important events for the quality control of mitochondria and mitochondrial-associated diseases. Esculetin (ESC) is a natural coumarin that exhibits inspiring biological activities in a variety of animal models, but its neuroprotective effects on cerebral ischaemia have not been clearly elucidated. In this paper, we demonstrated the effects of ESC on transient cerebral ischaemia and reperfusion injury induced in a mouse model and examined the possible underlying mechanisms by investigating mitochondrial fragmentation-regulated mitochondrial autophagy and apoptosis. The experimental results showed that ESC treatment alleviated neurological defects and improved cognitive impairments in transient bilateral common carotid artery occlusion (tBCCAO)-treated mice. Further mechanism studies showed that tBCCAO induced mitochondrial oxidative stress injuries and triggered mitochondrial fragmentation, which were evident by the elevated levels of malondialdehyde and mitochondrial dynamin-related protein 1 (Drp1) and the downregulated activities of superoxide dismutase and nuclear transcription factor E2-rela...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research

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Very few of the presently available interventions for aging are forms of rejuvenation, and of these most are debatable or have small, unreliable effects. Beyond senolytic drugs to clear some fraction of senescent cells from aging tissues, an approach that is producing sizable, reliable effects in animal studies and that will soon enough become a major part of healthcare for the old, other present treatments can only be argued to be forms of rejuvenation. Either they are not addressing root cause damage, or their effect sizes are so marginal as to make it unclear as to whether anything interesting is taking place. Consider ...
Source: Fight Aging! - Category: Research Authors: Tags: Activism, Advocacy and Education Source Type: blogs
Publication date: Available online 21 August 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Ju Gao, Luwen Wang, Tingxiang Yan, George Perry, Xinglong WangAbstractGenetic mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Importantly, TDP-43 proteinopathy, characterized by aberrant phosphorylation, ubiquitination, cleavage or nuclear depletion of TDP-43 in neurons and glial cells, is a common prominent pathological feature of various major neurodegenerative diseases including ALS, FTD, and Alzheimer's disease (AD). Although the pathomechan...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
ConclusionCa2+ regulation influences the neurodegenerative process and there is possible role for perturbed calcium signaling in Mn neurotoxicity. Mechanisms implicated in Mn-induced neurodegeneration include oxidative stress, generation of free radicals, and apoptosis. These are influenced by mitochondrial integrity which can be dependent on intracellular Ca2+ homeostasis. Nevertheless, further elucidation of the direct effects of calcium signaling dysfunction and calcium-binding proteins activities in Mn neurotoxicity is required.
Source: Journal of Trace Elements in Medicine and Biology - Category: Biochemistry Source Type: research
Publication date: November 2019Source: Journal of Functional Foods, Volume 62Author(s): Xuyun Liu, Ke Cao, Weiqiang Lv, Jing Liu, Jing Gao, Yan Wang, Chuan Qin, Jianshu Liu, Weijin Zang, Jiankang LiuAbstractIncreasing evidence demonstrates that hyperlipidemia plays a causal role in the development of cardiovascular diseases (CVDs) due to endothelial dysfunction. Houttuynia cordata aqueous extract (HAE), using as both medicine and food, whose effect and mechanism were investigated in endothelial dysfunction. In vivo, it profoundly attenuated hyperlipidemia-induced accumulation of serum metabolites, which in turn contributed...
Source: Journal of Functional Foods - Category: Nutrition Source Type: research
We report two siblings, from consanguineous parents, harbouring a previously uncharacterized homozygous variant in FBXL4 (c.1750 T > C; p.Cys584Arg). Both patients presented with encephalomyopathy, lactic acidosis and cardiac hypertrophy, which are reported features of FBXL4 impairment. Remarkably, dichloroacetate (DCA) administration to the younger sibling improved metabolic acidosis and reversed cardiac hypertrophy. Characterization of FBXL4 patient fibroblasts revealed severe bioenergetic defects, mtDNA depletion, fragmentation of mitochondrial networks, and abnormalities in mtDNA nucleoids. These phenotypes, o...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
The scientific community is saddened by the passing of Walter Neupert, an exceptional scientist and outstanding mentor, who contributed to shaping molecular cell biology over a career that spanned more than five decades. As a founder of the field of mitochondrial protein biogenesis, his research provided key mechanistic insights  into the fundamental process of cellular protein sorting and membrane translocation. Mitochondria have an important role in metabolism and cell regulation, and defects in their functions are a major cause of human diseases.
Source: Molecular Cell - Category: Cytology Authors: Tags: Obituary Source Type: research
GDF-15, a member of the transforming growth factor beta superfamily, regulates inflammatory and apoptotic pathways in various diseases, such as heart failure, kidney dysfunction, and cancer. We aimed to clarify potentially confounding variables affecting GDF-15 and demonstrate its utility as a mitochondrial biomarker using serum samples from 15 patients with mitochondrial diseases (MD), 15 patients with limbic encephalitis (LE), 10 patients with multiple sclerosis/neuromyelitis optica spectrum disorders (MS/NMOSD), and 19 patients with amyotrophic lateral sclerosis (ALS).
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Source Type: research
Publication date: Available online 21 August 2019Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Monokesh K. Sen, David A. Mahns, Jens R. Coorssen, Peter J. ShortlandAbstractThe feeding of cuprizone (CPZ) to animals has been extensively used to model the processes of demyelination and remyelination, with many papers adopting a narrative linked to demyelinating conditions like multiple sclerosis (MS), the aetiology of which is unknown. However, no current animal model faithfully replicates the myriad of symptoms seen in the clinical condition of MS. CPZ ingestion causes mitochondrial and endoplasmic reticulum stre...
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research
Mitochondrial disorders are clinically and genetically heterogeneous and are caused by mutations in genes of both mitochondrial DNA (mtDNA) and nuclear DNA. Of the mtDNA point mutations causing mitochondrial disease, ∼50% involve mitochondrial (mt-)tRNA genes [1–3]. Pathogenic mt-tRNA mutations typically display heteroplasmy, the presence of both wild type and mutant mtDNA molecules in a cell, and are often associated with the presence of focal ragged red fibres (RRFs) and cytochrome c oxidase (COX)-deficien t fibres in skeletal muscle, leading to a combined respiratory chain deficiency reflecting a disorder of g...
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Conclusion and Implications: Midkine is elevated in human and porcine plasma after multiple trauma, affecting the functionality and metabolism of human cardiomyocytes in vitro. If the application of CytoSorb300 filtration for patients after multiple trauma is a promising therapeutic approach to prevent post-traumatic cardiac dysfunction requires further examination.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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