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Mitochondrial brain

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https://www.readbyqxmd.com/read/27926857/a-lon-clpp-proteolytic-axis-degrades-complex-i-to-extinguish-ros-production-in-depolarized-mitochondria
#1
Kenneth Robert Pryde, Jan Willem Taanman, Anthony Henry Schapira
Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and in Parkinson's disease (PD) in particular. PINK1 and Parkin gene mutations are causes of autosomal recessive PD, and these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It is widely assumed that impaired mitophagy causes PD, as toxic reactive oxygen species (ROS)-producing mitochondria accumulate and progressively drive neurodegeneration. Instead, we report that a LON-ClpP proteolytic quality control axis extinguishes ROS in depolarized mitochondria by degrading the complex I ROS-generating domain...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27924409/antioxidants-reverse-the-changes-in-energy-metabolism-of-rat-brain-after-chronic-administration-of-l-tyrosine
#2
Brena P Teodorak, Giselli Scaini, Milena Carvalho-Silva, Lara M Gomes, Letícia J Teixeira, Joyce Rebelo, Samira D T De Prá, Neila Zeni, Patrícia F Schuck, Gustavo C Ferreira, Emilio L Streck
Tyrosinemia type II is a rare autosomal recessive disease caused by deficiency of hepatic tyrosine aminotransferase and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that high concentrations of tyrosine provoke mitochondrial dysfunction and oxidative stress, in the present study we investigated the in vivo influence of antioxidants (N-acetylcysteine, NAC; and deferoxamine, DFX) administration on the inhibitory effects on parameters of energy metabolism in cerebral cortex, hippocampus and striatum of rats, provoked by chronic administration of L...
December 6, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27924223/mitochondrial-permeability-transition-pore-induction-is-linked-to-formation-of-the-complex-of-atpase-c-subunit-polyhydroxybutyrate-and-inorganic-polyphosphate
#3
P A Elustondo, M Nichols, A Negoda, A Thirumaran, E Zakharian, G S Robertson, E V Pavlov
Mitochondrial permeability transition pore (mPTP) opening allows free movement of ions and small molecules leading to mitochondrial membrane depolarization and ATP depletion that triggers cell death. A multi-protein complex of the mitochondrial ATP synthase has an essential role in mPTP. However, the molecular identity of the central 'pore' part of mPTP complex is not known. A highly purified fraction of mammalian mitochondria containing C-subunit of ATPase (C-subunit), calcium, inorganic polyphosphate (polyP) and polyhydroxybutyrate (PHB) forms ion channels with properties that resemble the native mPTP...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27921253/aberrant-alterations-of-mitochondrial-factors-drp1-and-opa1-in-the-brains-of-scrapie-experiment-rodents
#4
Xiao -Dong Yang, Qi Shi, Jing Sun, Yan Lv, Yue Ma, Cao Chen, Kang Xiao, Wei Zhou, Xiao-Ping Dong
The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#5
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27916896/the-impact-of-cxcr4-blockade-on-the-survival-of-rat-brain-cortical-neurons
#6
José Joaquín Merino, Alba Garcimartín, María Elvira López-Oliva, Juana Benedí, María Pilar González
BACKGROUND: Chemokine receptor type 4 (CXCR4) plays a role in neuronal survival/cell repair and also contributes to the progression of cancer and neurodegenerative diseases. Chemokine ligand 12 (CXCL12) binds to CXCR4. In this study, we have investigated whether CXCR4 blockade by AMD3100 (a CXCR4 antagonist, member of bicyclam family) may affect neuronal survival in the absence of insult. Thus, we have measured the mitochondrial membrane potential (MMP), Bax and Bcl-2 protein translocation, and cytochrome c release in AMD3100-treated brain cortical neurons at 7 DIV (days in vitro)...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914013/inhibitory-effect-of-homocysteine-on-rat-neural-stem-cell-growth-in-vitro-is-associated-with-reduced-protein-levels-and-enzymatic-activities-of-aconitase-and-respiratory-complex-iii
#7
Xu-Mei Zhang, Ya-Qian Zhao, Hai Yan, Huan Liu, Guo-Wei Huang
Increased blood plasma concentration of the sulphur amino acid homocysteine (Hcy) is considered as an independent risk factor of the neurodegenerative diseases. However, the detailed molecular mechanisms by which Hcy leads to neurotoxicity have yet to be clarified. Recent research has suggested that neurotoxicity of Hcy may involve negative regulation of neural stem cell (NSC) proliferation. In the current study, primary NSCs were isolated from neonatal rat brain hippocampus and the inhibition in cell growth was observed after exposure to l50 μM and 500 μM L-Hcy...
December 2, 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27911398/evaluation-of-bioenergetic-function-in-cerebral-vascular-endothelial-cells
#8
Stephanie L Rellick, Heng Hu, James W Simpkins, Xuefang Ren
The integrity of the blood-brain-barrier (BBB) is critical to prevent brain injury. Cerebral vascular endothelial (CVE) cells are one of the cell types that comprise the BBB; these cells have a very high-energy demand, which requires optimal mitochondrial function. In the case of disease or injury, the mitochondrial function in these cells can be altered, resulting in disease or the opening of the BBB. In this manuscript, we introduce a method to measure mitochondrial function in CVE cells by using whole, intact cells and a bioanalyzer...
November 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911307/a-high-cholesterol-diet-increases-27-hydroxycholesterol-and-modifies-estrogen-receptor-expression-and-neurodegeneration-in-rabbit-hippocampus
#9
Sylwia W Brooks, Ava C Dykes, Bernard G Schreurs
Hypercholesterolemia has been implicated in numerous health problems from cardiovascular disease to neurodegeneration. High serum cholesterol levels in midlife have been associated with an increased risk of developing Alzheimer's disease (AD) later in life which suggests that the pathways leading to AD pathology might be activated decades before the symptoms of the disease are detected. Cholesterol-fed animals, particularly cholesterol-fed rabbits, exhibit brain pathology similar to the changes found in brains of AD patients...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27909264/global-ablation-of-the-mitochondrial-calcium-uniporter-increases-glycolysis-in-cortical-neurons-subjected-to-energetic-stressors
#10
Matthew Nichols, Pia A Elustondo, Jordan Warford, Aruloli Thirumaran, Evgeny V Pavlov, George S Robertson
The effects of global mitochondrial calcium (Ca(2+)) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca(2+) handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca(2+) uptake and Ca(2+)-induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage...
December 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27909098/reversible-disruption-of-neuronal-mitochondria-by-ischemic-and-traumatic-injury-revealed-by-quantitative-two-photon-imaging-in-the-neocortex-of-anesthetized-mice
#11
Mikhail Kislin, Jeremy Sword, Ioulia V Fomitcheva, Deborah Croom, Evgeny Pryazhnikov, Eero Lihavainen, Dmytro Toptunov, Heikki Rauvala, Andre S Ribeiro, Leonard Khiroug, Sergei A Kirov
: Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under such pathological conditions as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries ranging from severe to mild...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#12
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908258/neurotoxicity-induced-by-mephedrone-an-up-to-date-review
#13
Flaminia Pantano, Roberta Tittarelli, Giulio Mannocchi, Roberta Pacifici, Alessandro di Luca, Francesco Paolo Busardò, Enrico Marinelli
Mephedrone is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential. The aim of this review was to examine the emerging scientific literature on the possible mephedrone-induced neurotoxicity, yet not well defined due to the limited number of experimental studies, mainly carried on animal models. Relevant scientific articles were identified from international literature databases (Medline, Scopus, etc...
November 30, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27904950/age-dependent-alpha-synuclein-accumulation-is-correlated-with-elevation-of-mitochondrial-trpc3-in-the-brains-of-monkeys-and-mice
#14
Min Chen, Jia Liu, Yongquan Lu, Chunli Duan, Lingling Lu, Ge Gao, Piu Chan, Shun Yu, Hui Yang
Aberrant α-synuclein (α-syn) accumulation has been shown to impair mitochondrial function by reducing mitochondrial membrane potential (MMP). However, the underlying mechanisms remain elusive. Transient receptor potential canonical (TRPC) channels are a diverse group of non-selective Ca(2+) channels, among which TRPC3 is the only one that is localized in mitochondria and plays a role in maintaining the normal MMP. This raises a possibility that altered TRPC3 expression may play a role in the mitochondrial dysfunction induced by α-syn accumulation...
November 30, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27902774/intravenous-treatment-with-a-long-chain-omega-3-lipid-emulsion-provides-neuroprotection-in-a-murine-model-of-ischemic-stroke-a-pilot-study
#15
Dirk Berressem, Konrad Koch, Nicole Franke, Jochen Klein, Gunter P Eckert
Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO...
2016: PloS One
https://www.readbyqxmd.com/read/27902528/increased-brain-lactate-during-depressive-episodes-and-reversal-effects-by-lithium-monotherapy-in-drug-naive-bipolar-disorder-a-3-t-1h-mrs-study
#16
Rodrigo Machado-Vieira, Marcus V Zanetti, Maria C Otaduy, Rafael T De Sousa, Marcio G Soeiro-de-Souza, Alana C Costa, Andre F Carvalho, Claudia C Leite, Geraldo F Busatto, Carlos A Zarate, Wagner F Gattaz
OBJECTIVE: Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD...
November 28, 2016: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27901512/mitochondrial-dysfunction-in-alveolar-and-white-matter-developmental-failure-in-premature-infants
#17
Vadim S Ten
At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants...
November 30, 2016: Pediatric Research
https://www.readbyqxmd.com/read/27901032/from-the-past-to-future-from-energy-expenditure-to-energy-intake-to-energy-expenditure
#18
REVIEW
M J Müller, C Geisler
Although most recent research on energy balance focusses on energy intake (EI) there is still need to think about both sides of the energy balance. Current research on energy expenditure (EE) relates to metabolic adaptation to negative energy balance, mitochondrial metabolism associated with aging, obesity and type 2 diabetes mellitus, the role of EE in hunger and appetite control, non-shivering thermogenesis and brown adipose tissue activity, cellular bioenergetics as a target of obesity treatment and the evolutionary and ecological determinants of EE in humans and other primates...
November 30, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27898072/elevated-brain-lactate-in-schizophrenia-a-7%C3%A2-t-magnetic-resonance-spectroscopy-study
#19
L M Rowland, S Pradhan, S Korenic, S A Wijtenburg, L E Hong, R A Edden, P B Barker
Various lines of evidence suggest that brain bioenergetics and mitochondrial function may be altered in schizophrenia. On the basis of prior phosphorus-31 ((31)P)-magnetic resonance spectroscopy (MRS), post-mortem and preclinical studies, this study was designed to test the hypothesis that abnormal glycolysis leads to elevated lactate concentrations in subjects with schizophrenia. The high sensitivity of 7 Tesla proton ((1)H)-MRS was used to measure brain lactate levels in vivo. Twenty-nine controls and 27 participants with schizophrenia completed the study...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27897111/aggressive-antioxidant-reductive-stress-impairs-brain-endothelial-cell-angiogenesis-and-blood-brain-barrier-function
#20
Shireen Mentor, David Fisher
Oxidative stress in the brain microvasculature is a common characteristic in models of cerebrovascular disease. Considering the effects of reactive oxygen species activity in vascular-derived insults, it is naturally prudent to hypothesize those interventions inhibiting reactive oxygen species activity, such as antioxidant supplementation, may be beneficial for cerebrovascular disease. Hyper doses of antioxidant supplements, and foods with high antioxidant concentrations, are commonly used as an ongoing remedial and 'over-the-counter' treatments for most seasonal ailments...
November 29, 2016: Current Neurovascular Research
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