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Mitochondria psychiatric

Erik A Ehli, Abdel Abdellaoui, Iryna O Fedko, Charlie Grieser, Sahar Nohzadeh-Malakshah, Gonneke Willemsen, Eco Jc de Geus, Dorret I Boomsma, Gareth E Davies, Jouke J Hottenga
As an example of optimizing population-specific genotyping assays using a whole-genome sequence reference set, we detail the approach that followed to design the Axiom-NL array which is characterized by an improved imputation backbone based on the Genome of the Netherlands (GoNL) reference sequence and, compared with earlier arrays, a more comprehensive inclusion of SNPs on chromosomes X, Y, and the mitochondria. Common variants on the array were selected to be compatible with the Illumina Psych Array and the Affymetrix UK Biobank Axiom array...
November 23, 2016: European Journal of Human Genetics: EJHG
Rodrigo A Quintanilla, Cheril Tapia, María José Pérez
Huntington disease (HD) is a devastating neurological disorder that affects the striatum and cortex of patients. HD patients develop progressive motor dysfunction and psychiatric disturbances with gradual dementia. HD is caused by a pathological expansion of CAG repeats in the huntingtin gene that codifies for a protein called huntingtin (Htt), which principal function is not completely understood. Accumulative evidence shows that this pathological expansion modifies Htt function affecting different neuronal targets, including mitochondrial function which is an important factor that contributes to HD...
September 13, 2016: Biochemical and Biophysical Research Communications
Miroslav Adzic, Zeljka Brkic, Sonja Bulajic, Milos Mitic, Marija B Radojcic
Preclinical Research Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms...
November 2016: Drug Development Research
Oded Bergman, Dorit Ben-Shachar
Mitochondria are key players in the generation and regulation of cellular bioenergetics, producing the majority of adenosine triphosphate molecules by the oxidative phosphorylation system (OXPHOS). Linked to numerous signaling pathways and cellular functions, mitochondria, and OXPHOS in particular, are involved in neuronal development, connectivity, plasticity, and differentiation. Impairments in a variety of mitochondrial functions have been described in different general and psychiatric disorders, including schizophrenia (SCZ), a severe, chronic, debilitating illness that heavily affects the lives of patients and their families...
August 2016: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Giselli Scaini, Gislaine T Rezin, Andre F Carvalho, Emilio L Streck, Michael Berk, João Quevedo
Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration...
September 2016: Neuroscience and Biobehavioral Reviews
Roghaiyeh Safari, Reza Salimi, Zeliha Tunca, Aysegul Ozerdem, Deniz Ceylan, Meral Sakizli
Calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. Impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (BP). MCU is the most important calcium transporter in mitochondria inner membrane responsible for influx of Ca[Formula: see text]. MICU1 is linked with MCU and has two canonical EF hands that are vital for its activity and regulates MCU-mediated Ca[Formula: see text] influx...
June 2016: Journal of Integrative Neuroscience
Qingzhong Wang, Yogesh Dwivedi
OBJECTIVES: Recent evidences suggest that mitochondrial dysfunction maybe involved in the pathophysiology of major depressive disorder (MDD); however, the role of mitochondrial genes in this disorder has not been studied systematically. In the present study, we profiled expression of mitochondrial genes in dorsolateral prefrontal cortex (dlPFC) of MDD and non-psychiatric control subjects. METHODS: Human mitochondrial RT(2) profile PCR array plates were used to examine differentially expressed genes in dlPFC of 11 MDD and 11 control subjects...
June 8, 2016: World Journal of Biological Psychiatry
Gretchen Hermes, David Nagy, Michael Waterson, Attila Zsarnovszky, Luis Varela, Mihaly Hajos, Tamas L Horvath
BACKGROUND/PURPOSE: Major psychiatric illnesses, affecting 36% of the world's population, are profound disorders of thought, mood and behavior associated with underlying impairments in synaptic plasticity and cellular resilience. Mitochondria support energy demanding processes like neural transmission and synaptogenesis and are thus points of broadening interest in the energetics underlying the neurobiology of mental illness. These experiments interrogated the importance of mitochondrial flexibility in behavior, synaptic and cortical activity in a mouse model...
June 2016: Molecular Metabolism
M J Devine, R Norkett, J T Kittler
The long, asymmetric and specialised architecture of neuronal processes necessitates a properly regulated transport network of molecular motors and cytoskeletal tracks. This allows appropriate distribution of cargo for correct formation and activity of the synapse, and thus normal neuronal communication. This communication is impaired in psychiatric disease, and ongoing studies have proposed that Disrupted in schizophrenia 1 (DISC1) is an important genetic risk factor for these disorders. The mechanisms by which DISC1 dysfunction might increase propensity to psychiatric disease are not completely understood; however, an emerging theme is that DISC1 can function as a key regulator of neuronal intracellular trafficking...
October 1, 2016: Journal of Physiology
Abdülhadi Cihangir Uguz, Kadir Demirci, Javier Espino
Mitochondria play a critical role in regulating cellular functions, such as redox signaling, calcium homeostasis, and apoptosis. Also, mitochondria are crucial for neurogenesis and neuronal functions. Melatonin is an indole analog hormone, which is generally produced by the pineal gland. It plays a vital role in circadian rhythm and act as a powerful antioxidant by scavenging free radicals, immunomodulators, and anticancer agents. Schizophrenia and mood disorders are the two major psychiatric disorders. Disturbances of sleep and circadian rhythms are well-known symptoms of schizophrenia and mood disorders (bipolar disorder, major depression)...
2016: Current Medicinal Chemistry
Dragana Filipović, Nevena Todorović, Rick E Bernardi, Peter Gass
Various stressors may disrupt the redox homeostasis of an organism by causing oxidative and nitrosative stress that may activate stressor-specific pathways and provoke specific responses. Chronic social isolation (CSIS) represents a mild chronic stress that evokes a variety of neurobehavioral changes in rats similar to those observed in people with psychiatric disorders, including depression. Most rodent studies have focused on the effect of social isolation during weaning or adolescence, while its effect in adult rats has not been extensively examined...
March 31, 2016: Brain Structure & Function
Stefania Schiavone, Luigia Trabace
Redox dysregulation occurs following a disequilibrium between reactive oxygen species (ROS) producing and degrading systems, i.e. mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and nitric oxide synthase (NOS) on one hand and the principal antioxidant system, the glutathione, on the other hand. Increasing recent evidence points towards a pathogenetic role of an altered redox state in the development of several mental disorders, such as anxiety, bipolar disorders, depression, psychosis, autism and post-traumaticstress disorders (PTSD)...
May 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Kamaljeet Kaur, Raja Fayad, Arpit Saxena, Norma Frizzell, Anindya Chanda, Suvarthi Das, Saurabh Chatterjee, Shweta Hegde, Manjeshwar Shrinath Baliga, Venkatesh Ponemone, Matthew Rorro, Jennifer Greene, Yasmine Elraheb, Alan J Redd, John Bian, John Restaino, LeAnn B Norris, Zaina P Qureshi, Bryan L Love, Brandon Brookstaver, Peter Georgantopoulos, Oliver Sartor, Dennis W Raisch, Gowtham Rao, Kevin Lu, Paul Ray, William Hrusheshky, Richard Schulz, Richard Ablin, Virginia Noxon, Charles L Bennett
BACKGROUND: The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia...
February 2016: Journal of Community and Supportive Oncology
Fumiaki Ogawa, Laura C Murphy, Elise L V Malavasi, Shane T O'Sullivan, Helen S Torrance, David J Porteous, J Kirsty Millar
Mitochondria are essential for neuronal function, providing the energy required to power neurotransmission, and fulfilling many important additional roles. In neurons, mitochondria must be efficiently transported to sites, including synapses, where their functions are required. Neurons, with their highly elongated morphology, are consequently extremely sensitive to defective mitochondrial trafficking which can lead to neuronal ill-health/death. We recently demonstrated that DISC1 associates with mitochondrial trafficking complexes where it associates with the core kinesin and dynein adaptor molecule TRAK1...
May 18, 2016: ACS Chemical Neuroscience
George Anderson, Aude Jacob, Frank Bellivier, Pierre Alexis Geoffroy
Bipolar disorder (BD) is a long-recognized severe and common psychiatric disorder, with a complex and often diverse range of presentations. BD is a heterogenous disorder that has traditionally, if rather simply, been defined by the recurrences of manic and depressive episodes, and presents with numerous immune-inflammatory and circadian/sleep abnormalities. A number of different lines of research have investigated the biological underpinnings of BD and demonstrate a heritability of about 80-90%. This genetic contribution is thought to be mediated by a wide array of genetic factors, rather than being strongly influenced by a couple of genes...
2016: Current Pharmaceutical Design
Helena Kyunghee Kim, Ana Cristina Andreazza, Nika Elmi, Wenjun Chen, L Trevor Young
Mitochondrial complex I dysfunction, oxidative stress and immune-activation are consistently reported in bipolar disorder (BD). Mitochondrial production of reactive oxygen species was recently linked to activation of an inflammatory redox sensor, the nod-like receptor family pyrin domain-containing 3 (NLRP3). Upon its activation, NLRP3 recruits apoptosis-associated speck-like protein (ASC) and caspase-1 to form the NLRP3-inflammasome, activating IL-1β. This study aimed to examine if immune-activation may be a downstream target of complex I dysfunction through the NLRP3-inflammasome in BD...
January 2016: Journal of Psychiatric Research
Laura E Clemens, Jonasz J Weber, Tanja T Wlodkowski, Libo Yu-Taeger, Magali Michaud, Carsten Calaminus, Schamim H Eckert, Janett Gaca, Andreas Weiss, Janine C D Magg, Erik K H Jansson, Gunter P Eckert, Bernd J Pichler, Thierry Bordet, Rebecca M Pruss, Olaf Riess, Huu P Nguyen
Huntington's disease is a fatal human neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene, which translates into a mutant huntingtin protein. A key event in the molecular pathogenesis of Huntington's disease is the proteolytic cleavage of mutant huntingtin, leading to the accumulation of toxic protein fragments. Mutant huntingtin cleavage has been linked to the overactivation of proteases due to mitochondrial dysfunction and calcium derangements. Here, we investigated the therapeutic potential of olesoxime, a mitochondria-targeting, neuroprotective compound, in the BACHD rat model of Huntington's disease...
December 2015: Brain: a Journal of Neurology
Tadasato Nagano, Makoto Mizuno, Keisuke Morita, Hiroyuki Nawa
Proinflammatory cytokines perturb brain development and neurotransmission and are implicated in various psychiatric diseases, such as schizophrenia and depression. These cytokines often induce the production of reactive oxygen species (ROS) and regulate not only cell survival and proliferation but also inflammatory process and neurotransmission. Under physiological conditions, ROS are moderately produced in mitochondria but are rapidly scavenged by reducing agents in cells. However, brain injury, ischemia, infection, or seizure-like neural activities induce inflammatory cytokines and trigger the production of excessive amounts of ROS, leading to abnormal brain functions and psychiatric symptoms...
October 17, 2015: Current Topics in Behavioral Neurosciences
Joël Bockaert, Philippe Marin
TOR (target of rapamycin) and its mammalian ortholog mTOR have been discovered in an effort to understand the mechanisms of action of the immunosuppressant drug rapamycin extracted from a bacterium of the Easter Island (Rapa Nui) soil. mTOR is a serine/threonine kinase found in two functionally distinct complexes, mTORC1 and mTORC2, which are differentially regulated by a great number of nutrients such as glucose and amino acids, energy (oxygen and ATP/AMP content), growth factors, hormones, and neurotransmitters...
October 2015: Physiological Reviews
Ping Wang, Randa S Eshaq, Charles K Meshul, Cynthia Moore, Rebecca L Hood, Nancy J Leidenheimer
GABAA receptors mediate fast inhibitory neurotransmission in the brain. Dysfunction of these receptors is associated with various psychiatric/neurological disorders and drugs targeting this receptor are widely used therapeutic agents. Both the efficacy and plasticity of GABAA receptor-mediated neurotransmission depends on the number of surface GABAA receptors. An understudied aspect of receptor cell surface expression is the post-translational regulation of receptor biogenesis within the endoplasmic reticulum (ER)...
2015: Frontiers in Cellular Neuroscience
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