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Mitochondrial psychiatry

R Derungs, G G Camici, R D Spescha, T Welt, C Tackenberg, C Späni, F Wirth, A Grimm, A Eckert, R M Nitsch, L Kulic
The mammalian ShcA adaptor protein p66(Shc) is a key regulator of mitochondrial reactive oxygen species (ROS) production and has previously been shown to mediate amyloid β (Aβ)-peptide-induced cytotoxicity in vitro. Moreover, p66(Shc) is involved in mammalian longevity and lifespan determination as revealed in the p66(Shc) knockout mice, which are characterized by a 30% prolonged lifespan, lower ROS levels and protection from age-related impairment of physical and cognitive performance. In this study, we hypothesized a role for p66(Shc) in Aβ-induced toxicity in vivo and investigated the effects of genetic p66(Shc) deletion in the PSAPP transgenic mice, an established Alzheimer's disease mouse model of β-amyloidosis...
July 19, 2016: Molecular Psychiatry
Elham Ahmadian, Aziz Eftekhari, Javad Khalili Fard, Hossein Babaei, Alireza Mohajjel Nayebi, Daryoush Mohammadnejad, Mohammad Ali Eghbal
Even though citalopram is commonly used in psychiatry, there are several reports on its toxic effects. So, the current study was designed to elucidate the mechanisms of cytotoxic effects of in vitro and in vivo citalopram treatment on liver and the following cytolethal events. For in vitro experiments, freshly isolated rat hepatocytes were exposed to citalopram along with/without various agents. To do in vivo studies liver function enzyme assays and histological examination were performed. In the in vitro experiments, citalopram (500 µM) exposure demonstrated cell death, a marked elevation in ROS formation, mitochondrial potential collapse, lysosomal membrane leakiness, glutathione (GSH) depletion and lipid peroxidation...
June 6, 2016: Archives of Pharmacal Research
J Ernst, A Hock, A Henning, E Seifritz, H Boeker, S Grimm
There is ample evidence that glucose metabolism in the pregenual anterior cingulate cortex (PACC) is increased in major depressive disorder (MDD), whereas it is still unknown whether glucose levels per se are also elevated. Elevated cerebrospinal fluid (CSF) lactate concentrations in MDD patients might indicate that increased glycolytical metabolization of glucose to lactate in astrocytes either alone or in conjunction with mitochondrial dysfunction results in an accumulation of lactate and contributes to pathophysiological mechanisms of MDD...
January 2017: Molecular Psychiatry
P Devaraju, J Yu, D Eddins, M M Mellado-Lagarde, L R Earls, J J Westmoreland, G Quarato, D R Green, S S Zakharenko
Hemizygous deletion of a 1.5- to 3-megabase region on chromosome 22 causes 22q11.2 deletion syndrome (22q11DS), which constitutes one of the strongest genetic risks for schizophrenia. Mouse models of 22q11DS have abnormal short-term synaptic plasticity that contributes to working-memory deficiencies similar to those in schizophrenia. We screened mutant mice carrying hemizygous deletions of 22q11DS genes and identified haploinsufficiency of Mrpl40 (mitochondrial large ribosomal subunit protein 40) as a contributor to abnormal short-term potentiation (STP), a major form of short-term synaptic plasticity...
May 17, 2016: Molecular Psychiatry
H Wesseling, B Xu, E J Want, E Holmes, P C Guest, M Karayiorgou, J A Gogos, S Bahn
Deletions on chromosome 22q11.2 are a strong genetic risk factor for development of schizophrenia and cognitive dysfunction. We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A(+/-) mice, a model of the 22q11.2 deletion syndrome. Proteomic results were compared with previous transcriptomic profiling studies of the same brain regions. The aim was to investigate how the combined effect of the 22q11...
March 22, 2016: Molecular Psychiatry
N Yoshimi, T Futamura, S E Bergen, Y Iwayama, T Ishima, C Sellgren, C J Ekman, J Jakobsson, E Pålsson, K Kakumoto, Y Ohgi, T Yoshikawa, M Landén, K Hashimoto
Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls...
January 19, 2016: Molecular Psychiatry
M G Sharoar, Q Shi, Y Ge, W He, X Hu, G Perry, X Zhu, R Yan
Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains...
September 2016: Molecular Psychiatry
Deepmala, John Slattery, Nihit Kumar, Leanna Delhey, Michael Berk, Olivia Dean, Charles Spielholz, Richard Frye
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy...
August 2015: Neuroscience and Biobehavioral Reviews
D Arion, J P Corradi, S Tang, D Datta, F Boothe, A He, A M Cacace, R Zaczek, C F Albright, G Tseng, D A Lewis
Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3 and, to a lesser extent, in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell-type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression, specifically in DLPFC layer 3 or 5 pyramidal cells, would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness...
November 2015: Molecular Psychiatry
Hendrik Wesseling, Paul C Guest, Santiago G Lago, Sabine Bahn
Proteomic studies have increased our understanding of the molecular pathways affected in psychiatric disorders. Mass spectrometry and two-dimensional gel electrophoresis analyses of post-mortem brain samples from psychiatric patients have revealed effects on synaptic, cytoskeletal, antioxidant and mitochondrial protein networks. Multiplex immunoassay profiling studies have found alterations in hormones, growth factors, transport and inflammation-related proteins in serum and plasma from living first-onset patients...
August 2014: International Journal of Neuropsychopharmacology
Harold Andrew Sloas, Thomas C Ence, Donna R Mendez, Andrea T Cruz
Ornithine transcarbamylase (OTC) deficiency is a genetic disorder involving a mutation of the ornithine transcarbamylase gene, located on the short arm of the X chromosome (Xp21.1). This makes the expression of the gene most common in homozygous males, but heterozygous females can also be affected and may be more likely to suffer from serious morbidity. Most males present early in the neonatal period with more devastating outcomes than their female counterparts. Up to 34% will present in the first 30 days of life (J Pediatr 2001;138:S30)...
September 2013: American Journal of Emergency Medicine
Nagafumi Doi, Yoko Hoshi, Masanari Itokawa, Takeo Yoshikawa, Tomoe Ichikawa, Makoto Arai, Chie Usui, Hirokazu Tachikawa
BACKGROUND: Genetic research of schizophrenia (SCZ) based on the nuclear genome model (NGM) has been one of the most active areas in psychiatry for the past two decades. Although this effort is ongoing, the current situation of the molecular genetics of SCZ seems disappointing or rather perplexing. Furthermore, a prominent discrepancy between persistence of the disease at a relatively high prevalence and a low reproductive fitness of patients creates a paradox. Heterozygote advantage works to sustain the frequency of a putative susceptibility gene in the mitochondrial genome model (MGM) but not in the NGM...
2012: Behavioral and Brain Functions: BBF
Rebecca E Anglin, Sarah L Garside, Mark A Tarnopolsky, Michael F Mazurek, Patricia I Rosebush
OBJECTIVE: Mitochondrial disorders are caused by gene mutations in mitochondrial or nuclear DNA and affect energy-dependent organs such as the brain. Patients with psychiatric illness, particularly those with medical comorbidities, may have primary mitochondrial disorders. To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients. DATA SOURCES: This article describes a patient who presented with borderline personality disorder and treatment-resistant depression and was ultimately diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3271...
April 2012: Journal of Clinical Psychiatry
Valerie P Hans, David H Kaye, B Michael Dann, Erin J Farley, Stephanie Albertson
Questions about how jurors understand and apply scientific evidence were addressed in a mock jury study in which 480 jury pool members watched a videotaped mock trial that included expert testimony about mitochondrial DNA (mtDNA) evidence purportedly linking a defendant to a crime. Collectively, jurors showed moderately good comprehension of the mtDNA evidence, although some made definitional and inferential errors. Comprehension was better among jurors with higher educational attainment and more mathematics and science courses...
February 2011: Law and Human Behavior
J Rohayem, J-F Baylé, S Richa
INTRODUCTION: Since their first utilization in psychiatry as mood stabilizers in the 1940s, lithium salts have been widely studied in the medical literature. The considerable amount of data available to date, supports the use of lithium salts as first-line mood stabilizing agents, with acute antimanic and antidepressant properties and proven efficacy in the long term prevention of manic and depressive relapses. LITERATURE FINDINGS: Several predictors were reported by different authors in early articles and were confirmed later on by the medical literature...
September 2008: L'Encéphale
Brent P Forester, Chelsea T Finn, Yosef A Berlow, Megan Wardrop, Perry F Renshaw, Constance M Moore
OBJECTIVES: We investigated the relationship between brain lithium levels and the metabolites N-acetyl aspartate (NAA) and myo-inositol (myo-Ino) in the anterior cingulate cortex of a group of older adults with bipolar disorder (BD). METHODS: This cross-sectional assessment included nine subjects (six males and three females) with bipolar I disorder and currently treated with lithium, who were examined at McLean Hospital's Geriatric Psychiatry Research Program and Brain Imaging Center...
September 2008: Bipolar Disorders
Eniko Sáfrány, Veronika Csöngei, Luca Járomi, Anita Maász, Lili Magyari, Csilla Sipeky, Béla Melegh
The past two decades are considered as the golden age of the clinical research of mitochondrial DNA. The number of disease-associated pathologic variants is still expanding; the available knowledge about the entities caused by the abnormalities of the mitochondrial DNA is gradually increasing. The inheritance of the mitochondrial DNA exhibits maternal transmission; the properties are different from the nuclear genome in many respects. Albeit the establishment of correct diagnosis of several mitochondrial diseases still means diagnostic challenge, more and more entities can be identified due to the available molecular biology methods...
May 27, 2007: Orvosi Hetilap
Hikaru Aano
No abstract text is available yet for this article.
2006: Seishin Shinkeigaku Zasshi, Psychiatria et Neurologia Japonica
Anna Warchala, Krzysztof Kucia, Andrzej Małecki
Creatine kinase (CK) catalyzes the reversible transfer of the phosphoryl group from phosphocreatine to adenosine 5'-diphosphate (ADP), thus regenerating adenosine triphosphate (ATP). Creatine kinase genes are expressed in several tissues with high, fluctuating energy turnover, e.g. skeletal and cardiac muscle, brain and photoreceptor cells, and spermatozoa. Several isoenzymes of CK have been characterized: brain-type, muscle-type, and the hybrid isoenzymes, as well as the mitochondrial CK isoenzymes. Measurements of serum CK is a routine test in the diagnosis of acute myocardial infarction and various muscle disorders...
2006: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
W M Cowan, D H Harter, E R Kandel
One of the most significant developments in biology in the past half century was the emergence, in the late 1950s and early 1960s, of neuroscience as a distinct discipline. We review here factors that led to the convergence into a common discipline of the traditional fields of neurophysiology, neuroanatomy, neurochemistry, and behavior, and we emphasize the seminal roles played by David McKenzie Rioch, Francis O Schmitt, and especially Stephen W Kuffler in creating neuroscience as we now know it. The application of the techniques of molecular and cellular biology to the study of the nervous system has greatly accelerated our understanding of the mechanisms involved in neuronal signaling, neural development, and the function of the major sensory and motor systems of the brain...
2000: Annual Review of Neuroscience
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