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https://www.readbyqxmd.com/read/28721631/1-trichloromethyl-1-2-3-4-tetrahydro-beta-carboline-taclo-alters-cell-cycle-progression-in-human-neuroblastoma-cell-lines
#1
Rakesh Kumar Sharma, Eduardo Candelario-Jalil, Doris Feineis, Gerhard Bringmann, Bernd L Fiebich, Ravi Shankar Akundi
1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline, abbreviated as TaClo, is an endogenous neurotoxin capable of formation in the brain through the condensation of neuronal tryptamine with ingested exogenous toxins such as trichloroethylene or chloral hydrate. Due to its structural resemblance to 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and similar ability to inhibit mitochondrial complex I, TaClo has been implicated in the etiology of Parkinson's disease. Previous studies have shown the cytotoxicity of TaClo in various cell culture models...
July 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28720782/dysregulated-mirnas-and-their-pathogenic-implications-for-the-neurometabolic-disease-propionic-acidemia
#2
Ana Rivera-Barahona, Alejandro Fulgencio-Covián, Celia Pérez-Cerdá, Ricardo Ramos, Michael A Barry, Magdalena Ugarte, Belén Pérez, Eva Richard, Lourdes R Desviat
miRNome expression profiling was performed in a mouse model of propionic acidemia (PA) and in patients' plasma samples to investigate the role of miRNAs in the pathophysiology of the disease and to identify novel biomarkers and therapeutic targets. PA is a potentially lethal neurometabolic disease with patients developing neurological deficits and cardiomyopathy in the long-term, among other complications. In the PA mouse liver we identified 14 significantly dysregulated miRNAs. Three selected miRNAs, miR-34a-5p, miR-338-3p and miR-350, were found upregulated in brain and heart tissues...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720668/efficient-mitochondrial-glutamine-targeting-prevails-over-glioblastoma-metabolic-plasticity
#3
Kristell Oizel, Cynthia Chauvin, Lisa Oliver, Catherine Gratas, Fanny Geraldo, Ulrich Jarry, Emmanuel Scotet, Marion Rabe, Marie-Clotilde Alves-Guerra, Raluca Teusan, Fabien Gautier, Delphine Loussouarn, Vincent Compan, Jean-Claude Martinou, François M Vallette, Claire Pecqueur
Purpose Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer, however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof-of concept for personalized metabolic targeting of GBM. <p> Experimental Design We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays and mitochondrial respirometry...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28716632/mitochondrial-estrogen-receptors-as-a-vulnerability-factor-of-chronic-stress-and-mediator-of-fluoxetine-treatment-in-female-and-male-rat-hippocampus
#4
Miroslav Adzic, Milos Mitic, Marija Radojcic
Depression is a disease of an abnormal brain energy metabolism also marked with increased apoptosis in specific brain regions. Mounting evidence indicates that the mitochondrial oxidative phosphorylation and apoptosis are novel targets for the actions of estrogen receptors (ERs). In this study, we examined the effects of antidepressant (AD) fluoxetine (FLU) treatment on the mitochondrial ER alpha (ERα), ER beta (total and phospo-pERβ) and their association with cytochrome c (cyt c) oxidase activity and apoptotic Bcl2/Bax-molecules in the hippocampal mitochondria of chronically isolated (CPSI) female and male rats depicting depression...
July 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28716227/mitochondrial-trna-genes-are-hotspots-for-mutations-in-a-cohort-of-patients-with-exercise-intolerance-and-mitochondrial-myopathy
#5
Yuanyuan Lu, Danhua Zhao, Sheng Yao, Shiwen Wu, Daojun Hong, Qingqing Wang, Jing Liu, Jan A M Smeitink, Yun Yuan, Zhaoxia Wang
OBJECTIVE: Mitochondrial myopathy (MM) is a relatively rare type of mitochondrial disorder characterized by predominant skeletal muscle involvement. Both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) mutations have been reported as the genetic causes of this disease. Here, we described the clinical and genetic features of a cohort of patients with MM. METHODS: We conducted a retrospective, single center study enrolling 22 patients with clinically and myopathologically diagnosed MM...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28715601/methamphetamine-increases-prion-protein-and-induces-dopamine-dependent-expression-of-protease-resistant-prpsc
#6
M Ferrucci, L Ryskalin, F Biagioni, S Gambardella, C L Busceti, A Falleni, G Lazzeri, F Fornai
The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28714395/five-decades-of-cuprizone-an-updated-model-to-replicate-demyelinating-diseases
#7
Jose M Vega-Riquer, Gerardo Mendez-Victoriano, Raul A Morales-Luckie, Oscar Gonzalez-Perez
Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others comprise a group of demyelinating diseases characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter of the brain. To date, the etiology of these disorders is not well known and no effective treatments are currently available. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology of these diseases...
July 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28714328/neuronal-expression-of-the-mitochondrial-protein-prohibitin-confers-profound-neuroprotection-in-a-mouse-model-of-focal-cerebral-ischemia
#8
Anja Kahl, Corey J Anderson, Liping Qian, Henning Voss, Giovanni Manfredi, Costantino Iadecola, Ping Zhou
The mitochondrial protein prohibitin (PHB) has emerged as an important modulator of neuronal survival in different injury modalities . We previously showed that viral gene transfer of PHB protects CA1 neurons from delayed neurodegeneration following transient forebrain ischemia through mitochondrial mechanisms. However, since PHB is present in all cell types, it is not known if its selective expression in neurons is protective, and if the protection occurs also in acute focal ischemic brain injury, the most common stroke type in humans...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28712878/antidepressants-are-cytotoxic-to-rat-primary-blood-brain-barrier-endothelial-cells-at-high-therapeutic-concentrations
#9
Ekramy Elmorsy, Ayat Al-Ghafari, Fahd M Almutairi, Amal Misbah Aggour, Wayne G Carter
Antidepressants are commonly employed for the treatment of major depressive disorders and other psychiatric conditions. We investigated the relatively acute cytotoxic effects of three commonly prescribed antidepressants: fluoxetine, sertraline, and clomipramine on rat primary blood brain barrier endothelial cells over a concentration range of 0.1-100μM. At therapeutic concentrations (0.1μM) no significant cytotoxicity was observed after 4, 24, or 48h. At high therapeutic to overdose concentrations (1-100μM), antidepressants reduced cell viability in proportion to their concentration and exposure duration...
July 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28712340/deep-sequencing-reveals-the-mitochondrial-dna-variation-landscapes-of-breast-to-brain-metastasis-blood-samples
#10
Rhiannon E McGeehan, Lewis A Cockram, D Timothy J Littlewood, Kathleen Keatley, Diana M Eccles, Qian An
Breast-to-brain metastasis (BBM) often represents a terminal event, due to the inability of many systemic treatments to cross the blood-brain barrier (BBB), rendering the brain a sanctuary site for tumour cells. Identifying genetic variations that can predict the patients who will develop BBM would allow targeting of adjuvant treatments to reduce risk while disease bulk is minimal. Germ-line genetic variations may contribute to whether a BBM forms by influencing the primary tumour subtype that presents, or by influencing the host response to the tumour or treatment regimen, or by facilitating transition of tumour cells across the BBB and establish a viable brain metastasis...
July 15, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28710704/systemic-analysis-of-mirnas-in-pd-stress-condition-mir-5701-modulates-mitochondrial-lysosomal-cross-talk-to-regulate-neuronal-death
#11
Paresh Prajapati, Lakshmi Sripada, Kritarth Singh, Milton Roy, Khyati Bhatelia, Pooja Dalwadi, Rajesh Singh
Parkinson's disease (PD) is complex neurological disorder and is prevalent in the elderly population. This is primarily due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) region of the brain. The modulators of the selective loss of dopaminergic neurons in PD are still not well understood. The small non-coding RNAs specifically miRNAs fine-tune the protein levels by post-transcriptional gene regulation. The role of miRNAs in PD pathogenesis is still not well characterized. In the current study, we identified the miRNA expression pattern in 6-OHDA-induced PD stress condition in SH-SY5Y, dopaminergic neuronal cell line...
July 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28709994/metabolic-correction-by-pyruvate-halts-acquired-epilepsy-in-multiple-rodent-models
#12
I Popova, A Malkov, A I Ivanov, E Samokhina, S Buldakova, O Gubkina, A Osypov, T Zilberter, M Molchanov, S Paskevich, M Zilberter, Y Zilberter
Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to accumulated evidence that hypometabolism, manifested in humans as reduced brain glucose consumption, is a principal factor in acquired epilepsy. Therefore, targeting deficient energy metabolism may be an effective approach for treating epilepsy. To confront this pathology we utilized pyruvate, which besides being an anaplerotic mitochondrial fuel possesses a unique set of neuroprotective properties as it: (i) is a potent reactive oxygen species scavenger; (ii) abates overactivation of Poly [ADP-ribose] polymerase 1 (PARP-1); (iii) facilitates glutamate efflux from the brain; (iv) augments brain glycogen stores; (v) is anti-inflammatory; (vi) prevents neuronal hyperexcitability; and (vii) normalizes the cytosolic redox state...
July 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28708259/rapid-modulation-of-the-silent-information-regulator-1-sirt1-by-melatonin-after-hypoxia-ischemia-in-the-neonatal-rat-brain
#13
Silvia Carloni, Giulia Riparini, Giuseppe Buonocore, Walter Balduini
Increasing evidence indicates that melatonin possesses protective effects toward different kinds of damage in various organs, including the brain. In a neonatal model of hypoxia-ischemia (HI), melatonin was neuroprotective and preserved the expression of the Silent Information Regulator 1 (SIRT1) 24h after the insult. This study aimed to gain more insight into the role of SIRT1 in the protective effect of melatonin after HI by studying the early (1h) modulation of SIRT1 and its downstream targets, and the consequences on necrosis, apoptosis, autophagy and glial cell activation...
July 14, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28707399/neuroglobin-and-friends
#14
REVIEW
Marco Fiocchetti, Manuela Cipolletti, Valentina Brandi, Fabio Polticelli, Paolo Ascenzi
In the year 2000, the third member of the globin family was discovered in human and mouse brain and named neuroglobin (Ngb). Neuroglobin overexpression significantly protects both heart and brain from hypoxic/ischemic and oxidative stress-related insults, whereas decreased Ngb levels lead to an exacerbation of tissue injuries. Moreover, Ngb overexpression protects neurons from mitochondrial dysfunctions and neurodegenerative disorders such as Alzheimer disease; however, it facilitates the survival of cancer cells...
July 14, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28705594/induction-of-abcg2-bcrp-restricts-the-distribution-of-zidovudine-to-the-fetal-brain-in-rats
#15
María Fernanda Filia, Timoteo Marchini, Juan Mauricio Minoia, Martín Ignacio Roma, Fernanda Teresa De Fino, Modesto Carlos Rubio, Guillermo J Copello, Pablo A Evelson, Roxana Noemí Peroni
Safety concerns for fetus development of zidovudine (AZT) administration as prophylaxis of vertical transmission of HIV persist. We evaluated the participation of the ATP-binding cassette efflux transporter ABCG2 in the penetration of AZT into the fetal brain and the relevance for drug safety. Oral daily doses of AZT (60mg/kg body weight) or its vehicle were administered between post gestational days 11 (E11) and 20 (E20) to Sprague-Dawley pregnant rats. At E21, animals received an intravenous bolus of 60mg AZT/kg body weight in the presence or absence of the ABCG2 inhibitor gefitinib (20mg/kg body weight, ip) and AZT in maternal plasma and fetal brain were measured by HPLC-UV...
July 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28702935/vitamin-d3-attenuates-cognitive-deficits-and-neuroinflammatory-responses-in-icv-stz-induced-sporadic-alzheimer-s-disease
#16
P Yamini, R S Ray, Kanwaljit Chopra
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intracellular neurofibrillary tangles and extracellular Aβ deposition. Growing experimental evidence indicate diverse biological effects of vitamin D3 including antioxidant, neuroprotective, anti-inflammatory and cardiovascular benefits. However, the underlying neuroprotective mechanism of vitamin D3 is still largely elusive. Therefore, the present study was aimed to investigate the neuroprotective effects of vitamin D3 on ICV-STZ induced sporadic AD...
July 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28698101/coenzyme-q10-ameliorates-cerebral-ischemia-reperfusion-injury-in-hyperglycemic-rats
#17
Cui-Jie Lu, Yong-Zhen Guo, Yang Zhang, Lan Yang, Yue Chang, Jing-Wen Zhang, Li Jing, Jian-Zhong Zhang
The purpose of this study is to investigate the effect of coenzyme Q10 (CoQ10) on focal cerebral ischemia/reperfusion (I/R) injury in hyperglycemic rats and the possible involved mechanisms. In this study, we established the transient middle cerebral artery occlusion (MCAO) for 30min in the rats with diabetic hyperglycemia. The neurological deficit score, 2,3,5-triphenyltetrazolium chloride (TTC) staining and pathohistology are applied to detect the extent of the damage. The expression of Fis1, Mfn2 and Lc3 in the brain is investigated by immunohistochemical and Western blotting techniques...
June 15, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28697276/comparative-proteomic-study-of-early-hypoxic-response-in-the-cerebral-cortex-of-rats-submitted-to-two-different-hypoxic-models
#18
David Ovelleiro, Santos Blanco, Raquel Hernández, María Ángeles Peinado
PURPOSE: The present study analyses and compares the cortical brain proteomic profiles of two different models of cerebral hypoxic insult in rats (HH: hypobaric hypoxia and HHI: ischemia followed by hypobaric hypoxia) in an attempt to describe the alterations of the early molecular hypoxic adaptive response underlying each one. EXPERIMENTAL DESIGN: A quantitative proteomic profile of left-brain cortices of rats under HH, HHI and control conditions was determined using isobaric labeling (TMT) on the protein extracts from pools of five individuals...
July 11, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28695547/human-immunodeficiency-virus-promotes-mitochondrial-toxicity
#19
REVIEW
Summer J Rozzi, Valeria Avdoshina, Jerel A Fields, Margarita Trejo, Hoai T Ton, Gerard P Ahern, Italo Mocchetti
Combined antiretroviral therapies (cART) have had remarkable success in reducing morbidity and mortality among patients infected with human immunodeficiency virus (HIV). However, mild forms of HIV-associated neurocognitive disorders (HAND), characterized by loss of synapses, remain. cART may maintain an undetectable HIV RNA load but does not eliminate the expression of viral proteins such as trans-activator of transcription (Tat) and the envelope glycoprotein gp120 in the brain. These two viral proteins are known to promote synaptic simplifications by several mechanisms, including alteration of mitochondrial function and dynamics...
July 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28694756/electro-pharmacological-profiles-of-two-brain-mitoplast-anion-channels-inferences-from-single-channel-recording
#20
Javad Fahanik-Babaei, Farzad Shayanfar, Naser Khodaee, Reza Saghiri, Afsaneh Eliassi
We have characterized the conduction and blocking properties of two different chloride channels from brain mitochondrial inner membranes after incorporation into planar lipid bilayers. Our experiments revealed the existence of channels with a mean conductance of 158 ± 7 and 301 ± 8 pS in asymmetrical 200 mM cis/50 mM trans KCl solutions. We determined that the channels were ten times more permeable for Cl(-) than for K(+), calculated from the reversal potential using the Goldman-Hodgkin-Katz equation. The channels were bell-shaped voltage dependent, with maximum open probability 0...
2017: EXCLI journal
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