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https://www.readbyqxmd.com/read/29239317/%C3%AE-n-bcl-xl-a-therapeutic-target-for-neuroprotection
#1
REVIEW
Han-A Park, Elizabeth A Jonas
The B-cell lymphoma-extra large (Bcl-xL) is a mitochondrial anti-apoptotic protein that plays a role in neuroprotection. However, during excitotoxic stimulation, Bcl-xL undergoes caspase-dependent cleavage and produces a fragmented form, ΔN-Bcl-xL. Accumulation of ΔN-Bcl-xL is associated with mitochondrial dysfunction and neuronal death. Therefore, strategies to inhibit the activity or formation of ΔN-Bcl-xL protect the brain against excitotoxic injuries. Our team found that the pharmacological inhibitor ABT-737 exerts dose dependent effects in primary neurons...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29239022/fndc5-knockdown-induced-suppression-of-mitochondrial-integrity-and-significantly-decreased-cardiac-differentiation-of-mouse-embryonic-stem-cells
#2
Shima Nazem, Farzaneh Rabiee, Kmaran Ghaedi, Sadegh Babashah, Majid Sadeghizadeh, Mohammad Hossein Nasr-Esfahani
Fibronectin type III domain-containing 5 protein (Fndc5) is a glycosylated protein with elevated expression in high energy demanded tissues as heart, brain and muscle. It has been shown that upregulation of Fndc5 is regulated by peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which is known as a master regulator of mitochondrial function and biogenesis. Also, our group indicated that Fndc5 expression increases gradually during cardiac differentiation of mouse embryonic stem cells (mESCs)...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235496/involvement-of-trpm2-and-trpv1-channels-on-hyperalgesia-apoptosis-and-oxidative-stress-in-rat-fibromyalgia-model-protective-role-of-selenium
#3
Esra Yüksel, Mustafa Nazıroğlu, Mehmet Şahin, Bilal Çiğ
Fibromyalgia (FM) results in pain characterized by low selenium (Se) levels, excessive Ca2+ influx, reactive oxygen species (ROS) production, and acidic pH. TRPM2 and TRPV1 are activated by ROS and acid; nevertheless, their roles have not been elucidated in FM. Therefore, we investigated the contribution of TRPM2 and TRPV1 to pain, oxidative stress, and apoptosis in a rat model of FM and the therapeutic potential of Se. Thirty-six rats were divided into four groups: control, Se, FM, and FM + Se. The Se treatment reduced the FM-induced increase in TRPM2 and TRPV1 currents, pain intensity, intracellular free Ca2+, ROS, and mitochondrial membrane depolarization in the sciatic (SciN) and dorsal root ganglion (DRGN) neurons...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228978/asiatic-acid-attenuates-methamphetamine-induced-neuroinflammation-and-neurotoxicity-through-blocking-of-nf-kb-stat3-erk-and-mitochondria-mediated-apoptosis-pathway
#4
Ji-Hyun Park, Young Ho Seo, Jung-Hee Jang, Chul-Ho Jeong, Sooyeun Lee, Byoungduck Park
BACKGROUND: Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29228215/mitochondria-are-critical-for-bdnf-mediated-synaptic-and-vascular-plasticity-of-hippocampus-following-repeated-electroconvulsive-seizures
#5
Fenghua Chen, Maryam Ardalan, Betina Elfving, Gregers Wegener, Torsten M Madsen, Jens R Nyengaard
Background: Electroconvulsive therapy (ECT) is a fast acting and efficient treatment of depression used in the clinic. The underlying mechanism of its therapeutic effect is still unclear. However, recovery of synaptic connections and synaptic remodeling is thought to play a critical role for the clinical efficacy obtained from a rapid antidepressant response. Here, we investigated the relationship between, synaptic changes and concomitant non-neuronal changes in microvasculature and mitochondria, and it relationship to Brain-derived neurotrophic factor (BDNF) level changes after repeated electroconvulsive seizures (ECS), an animal model of ECT...
December 8, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29226520/a-novel-homozygous-slc25a1-mutation-with-impaired-mitochondrial-complex-v-possible-phenotypic-expansion
#6
Idan Cohen, Orna Staretz-Chacham, Ohad Wormser, Yonatan Perez, Ann Saada, Rotem Kadir, Ohad S Birk
SLC25A1 mutations are associated with combined D,L-2-hydroxyglutaric aciduria (DL- 2HGA; OMIM #615182), characterized by muscular hypotonia, severe neurodevelopmental dysfunction and intractable seizures. SLC25A1 encodes the mitochondrial citrate carrier (CIC), which mediates efflux of the mitochondrial tricarboxylic acid (TCA) cycle intermediates citrate and isocitrate in exchange for cytosolic malate. Only a single family with an SLC25A1 mutation has been described in which mitochondrial respiratory chain dysfunction was documented, specifically in complex IV...
December 11, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29225347/accelerated-epigenetic-aging-and-mitochondrial-dna-copy-number-in-bipolar-disorder
#7
Gabriel R Fries, Isabelle E Bauer, Giselli Scaini, Mon-Ju Wu, Iram F Kazimi, Samira S Valvassori, Giovana Zunta-Soares, Consuelo Walss-Bass, Jair C Soares, Joao Quevedo
Bipolar disorder (BD) has been previously associated with accelerated aging; yet, the mechanisms underlying this association are largely unknown. The epigenetic clock has been increasingly recognized as a valuable aging marker, although its association with other biological clocks in BD patients and high-risk subjects, such as telomere length and mitochondrial DNA (mtDNA) copy number, has never been investigated. We included 22 patients with BD I, 16 siblings of BD patients, and 20 healthy controls in this analysis...
December 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29225013/succinate-dehydrogenase-prospect-for-neurodegenerative-diseases
#8
REVIEW
Mohammad Jodeiri Farshbaf, Abbas Kiani-Esfahani
Onset of Alzheimer's, Parkinson's and Huntington's diseases as neurodegenerative disorders is increased by age. Alleviation of clinical symptoms and protection of neurons against degeneration are the main aspects of researches to establish new therapeutic strategies. Many studies have shown that mitochondria play crucial roles in high energy demand tissues like brain. Impairments in mitochondrial activity and physiology can makes neurons vulnerable to stress and degeneration. Succinate dehydrogenase (SDH) connects tricarboxylic cycle to the electron transport chain...
December 7, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29223874/the-hypoxia-tolerant-vertebrate-brain-arresting-synaptic-activity
#9
Leslie T Buck, Matthew E Pamenter
The ion channel arrest hypothesis has been the foundation of three decades of research into the underlying mechanisms of hypoxia/anoxia tolerance in several key species, including: painted turtles, goldfish, crucian carp, naked mole rats, and arctic and ground squirrels. The hypothesis originally stated that hypoxia/anoxia tolerant species ought to have fewer ion channels per area membrane and/or mechanisms to regulate the permeability of ions through channels. Today we can add to this and include mechanisms to remove channels from membranes and the expression of low conductance isoforms...
December 6, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29223124/activation-of-mitochondrial-katp-channels-mediates-neuroprotection-induced-by-chronic-morphine-preconditioning-in-hippocampal-ca-1-neurons-following-cerebral-ischemia
#10
Maedeh Arabian, Nahid Aboutaleb, Mansoureh Soleimani, Marjan Ajami, Rouhollah Habibey, Hamidreza Pazoki-Toroudi
PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury...
December 6, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/29219210/bioenergetic-regulation-of-microglia
#11
REVIEW
Soumitra Ghosh, Erika Castillo, Elma S Frias, Raymond A Swanson
Microglia have diverse actions, ranging from synapse pruning in development to cytotoxic effects in disease. Brain energy metabolism and substrate availability vary under normal and disease states, but how these variations influence microglial function is relatively unknown. Microglia, like most other cell types, express the full complement of gene products required for both glycolytic and oxidative metabolism. Evidence suggests that microglia increase aerobic glycolysis and decrease respiration when activated by various stimuli...
December 8, 2017: Glia
https://www.readbyqxmd.com/read/29218106/extracorporeal-shock-wave-therapy-effectively-protects-brain-against-chronic-cerebral-hypo-perfusion-induced-neuropathological-changes
#12
Han-Tan Chai, Kuan-Hung Chen, Christopher Glenn Wallace, Chih-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Chun-Man Yuen, Pei-Lin Shao, Cheuk-Kwan Sun, Hsueh-Wen Chang, Ching-Jen Wang, Mel S Lee, Hon-Kan Yip, Sheung-Fat Ko
This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy could protect mouse brain from chronic cerebral hypoperfusion (CHP)-induced neuropathological changes in a bilateral carotid arterial stenosis (CAS) model. Adult-male C57BL/6 (B6) mice (n=36) were randomized into group 1 (sham-control), group 2 (CHP) and group 3 [CHP+ECSW (100 impulses at 0.15 mJ/mm2) on day 5, 10 and 15 after CHP induction]. By day 60 after CHP induction, the white matter lesion, protein expressions of inflammatory (TNF-α/NF-κB/iNOS), oxidative-stress (NOX-1/NOX-2/NOX-4/nitrotyrosine), angiogenesis (eNOS/CD31), apoptotic (Bax/caspase-3/PARP), fibrotic (Smad3/TGF-ß) and mitochondrial-damaged (cytosolic cytochrome-C) biomarkers were significantly higher in group 2 than in groups 1 and 3, and significantly higher in group 3 than in group 1, whereas the protein expressions of anti-apoptotic (Bcl-2), anti-fibrotic (BMP-2/Smad1/5), and mitochondrial-integrity (mitochondrial cytochrome-C) biomarkers showed an opposite pattern to inflammation among the three groups (all P<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29211056/krebs-cycle-metabolites-and-preferential-succinate-oxidation-following-neonatal-hypoxic-ischemic-brain-injury-in-mice
#13
Prateek V Sahni, Jimmy Zhang, Sergey Sosunov, Alexander Galkin, Zoya Niatsetskaya, Anatoly Starkov, Paul S Brookes, Vadim S Ten
BackgroundReverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and H2O2 generation rate in the ischemic brain...
December 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29206478/lactate-is-oxidized-outside-of-the-mitochondrial-matrix-in-rodent-brain
#14
Eric A F Herbst, Mitchell A J George, Karen Brebner, Graham P Holloway, Daniel A Kane
The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine whether lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex and hippocampus (dorsal) subregions...
December 5, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29206066/magnesium-induces-preconditioning-of-the-neonatal-brain-via-profound-mitochondrial-protection
#15
Gabriella Koning, Anna-Lena Leverin, Syam Nair, Leslie Schwendimann, Joakim Ek, Ylva Carlsson, Pierre Gressens, Claire Thornton, Xiaoyang Wang, Carina Mallard, Henrik Hagberg
Magnesium sulphate (MgSO4) given to women in preterm labor reduces cerebral palsy in their offspring but the mechanism behind this protection is unclear, limiting its effective, safe clinical implementation. Previous studies suggest that MgSO4 is not neuroprotective if administered during or after the insult, so we hypothesised that MgSO4 induces preconditioning in the immature brain. Therefore, we administered MgSO4 at various time-points before/after unilateral hypoxia-ischemia (HI) in seven-day-old rats...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29205806/neuroprotection-by-quercetin-via-mitochondrial-function-adaptation-in-traumatic-brain-injury-pgc-1%C3%AE-pathway-as-a-potential-mechanism
#16
Xiang Li, Handong Wang, Guodao Wen, Liwen Li, Yongyue Gao, Zong Zhuang, Mengliang Zhou, Lei Mao, Youwu Fan
The aim of this study was to investigate the neuroprotective effects of quercetin in mouse models of traumatic brain injury (TBI) and the potential role of the PGC-1α pathway in putative neuroprotection. Wild-type mice were randomly assigned to four groups: the sham group, the TBI group, the TBI+vehicle group and the TBI+quercetin group. Quercetin, a dietary flavonoid used as a food supplement, significantly reduced TBI-induced neuronal apoptosis and ameliorated mitochondrial lesions. It significantly accelerated the translocation of PGC-1α protein from the cytoplasm to the nucleus...
December 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29205598/an-auditory-brainstem-nucleus-as-a-model-system-for-neuronal-metabolic-demands
#17
Sonja Brosel, Benedikt Grothe, Lars Kunz
The correlation between neuronal activity and metabolism is essential for coding, plasticity, neurological disorders and the interpretation of functional neuroimaging data. Most likely, metabolic requirements depend upon neuron type and macroscopic energy demands vary with brain region. However, specific needs of individual neuron types are enigmatic. Therefore, we monitored metabolic activity in the lateral superior olive (LSO), an auditory brainstem nucleus containing only one neuron type. LSO neurons exhibit extreme but well described biophysics with firing rates of several hundred hertz and low input resistances of a few megaohms...
December 4, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29204685/methylene-blue-protects-the-isolated-rat-lungs-from-ischemia-reperfusion-injury-by-attenuating-mitochondrial-oxidative-damage
#18
Wen-Fang Tian, Si Zeng, Qiong Sheng, Jun-Liang Chen, Ping Weng, Xiao-Tong Zhang, Jia-Jia Yuan, Qing-Feng Pang, Zhi-Qiang Wang
INTRODUCTION: Impaired mitochondrial function is a key factor attributing to the lung ischemia reperfusion injury (LIRI). Methylene blue (MB) has been reported to attenuate brain and renal ischemia-reperfusion injury. We hypothesized that MB also could have a protective effect against LIRI by preventing mitochondrial oxidative damage. METHODS: Isolated rat lungs were assigned to the following four groups (n = 6): a sham group: perfusion for 105 min without ischemia; I/R group: shutoff of perfusion and ventilation for 45 min followed by reperfusion for 60 min; and I/R + MB group and I/R + glutathione (GSH) group: 2 mg/kg MB or 4 μM glutathione were intraperitoneally administered for 2 h, and followed by 45 min of ischemia and 60 min of reperfusion...
December 4, 2017: Lung
https://www.readbyqxmd.com/read/29204109/intracellular-cholesterol-trafficking-and-impact-in-neurodegeneration
#19
REVIEW
Fabian Arenas, Carmen Garcia-Ruiz, Jose C Fernandez-Checa
Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29201196/lycium-barbarum-polysaccharide-protects-against-neurotoxicity-via-the-nrf2-ho-1-pathway
#20
Shumei Cao, Jianlong Du, Qiaohong Hei
The incidence of neurodegenerative diseases including Alzheimer's and Parkinson's disease has markedly increased over the past few decades. Oxidative stress is considered to be a common pathophysiological condition resulting in neurotoxicity. Lycium barbarum polysaccharide (LBP) is the major active component of Lycium barbarum L., which exhibit potent antioxidant activity. The current study investigated the neuroprotective effects of LBP in H2O2-treated PC12 cells in vitro and in CoCl2-treated rats in vivo...
November 2017: Experimental and Therapeutic Medicine
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