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Adenosine deaminase schizophrenia

Yuji Odagaki, Masakazu Kinoshita, Toshio Ota, J Javier Meana, Luis F Callado, Isao Matsuoka, Jesús A García-Sevilla
Adenosine signaling plays a complex role in multiple physiological processes in the brain, and its dysfunction has been implicated in pathophysiology of neuropsychiatric diseases such as schizophrenia and affective disorders. In the present study, the coupling between adenosine A1 receptor and G-protein was assessed by means of two [35 S]GTPγS binding assays, i.e., conventional filtration method and [35 S]GTPγS binding/immunoprecipitation in rat and human brain membranes. The latter method provides information about adenosine A1 receptor-mediated Gαi-3 activation in rat as well as human brain membranes...
June 2018: Purinergic Signalling
Sinead Marie O'Donovan, Courtney Sullivan, Rachael Koene, Emily Devine, Kathryn Hasselfeld, Cassidy Lynn Moody, Robert Erne McCullumsmith
Prior work in animal models implicates abnormalities of adenosine metabolism in astrocytes as a possible pathophysiological mechanism underlying the symptoms of schizophrenia. In the present study, we sought to reverse-translate these findings back to the human brain in schizophrenia, focusing on the following questions: (1) Which components of the adenosine system are dysregulated in schizophrenia, and (2) are these changes limited to astrocytes? To address these questions, we captured enriched populations of DLPFC pyramidal neurons and astrocytes from schizophrenia and control subjects using laser capture microdissection and assessed expression of adenosine system components using qPCR...
February 26, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Arun Sasidharan, Sunil Kumar, John P John, Mariamma Philip, Sarada Subramanian, Sanjeev Jain, Bindu M Kutty
The present study examined serum levels of adenosine deaminase (ADA), an adenosine metabolizing enzyme, in neuroleptic-naive patients with recent-onset schizophrenia and age-matched healthy comparison subjects. ADA levels were found to be higher among patients, and revealed a possible link between evening rise and severity of auditory hallucinations as well as morning rise and severity of avolition-apathy in patients with schizophrenia. These findings suggest the potential utility of serum ADA as a peripheral biomarker of schizophrenia...
October 2017: Asian Journal of Psychiatry
Kelly Juliana Seibt, Renata da Luz Oliveira, Mauricio Reis Bogo, Mario Roberto Senger, Carla Denise Bonan
Antipsychotic agents are used for the treatment of psychotic symptoms in patients with several brain disorders, such as schizophrenia. Atypical and typical antipsychotics differ regarding their clinical and side-effects profile. Haloperidol is a representative typical antipsychotic drug and has potent dopamine receptor antagonistic functions; however, atypical antipsychotics have been developed and characterized an important advance in the treatment of schizophrenia and other psychotic disorders. Purine nucleotides and nucleosides, such as ATP and adenosine, constitute a ubiquitous class of extracellular signaling molecules crucial for normal functioning of the nervous system...
December 2015: Fish Physiology and Biochemistry
Kadir Demirci, Ramazan Özçankaya, H Ramazan Yilmaz, Ayşe Yiğit, Abdülhadi Cihangir Uğuz, Kadir Karakuş, Arif Demirdaş, Abdullah Akpınar
OBJECTIVE: The treatment of schizophrenia is multifactorial, with antipsychotic medications comprising a major part of treatment. Paliperidone is a newly commercialized antipsychotic whose formulation includes the principal active metabolite risperidone, 9-hydroxyrisperidone. Ever since the relationship between schizophrenia and oxidative stress was first demonstrated, many studies have been conducted in order to probe the potential protective effects of antipsychotic drugs on the oxidant-antioxidant system and lipid peroxidation...
July 2015: Redox Report: Communications in Free Radical Research
Mie Kubota-Sakashita, Kazuya Iwamoto, Miki Bundo, Tadafumi Kato
BACKGROUND: Pre-mRNAs of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)-propanoic acid (AMPA)/kainate glutamate receptors undergo post-transcriptional modification known as RNA editing that is mediated by adenosine deaminase acting on RNA type 2 (ADAR2). This modification alters the amino acid sequence and function of the receptor. Glutamatergic signaling has been suggested to have a role in mood disorders and schizophrenia, but it is unknown whether altered RNA editing of AMPA/kainate receptors has pathophysiological significance in these mental disorders...
2014: Molecular Brain
Wojciech Garncarz, Aamira Tariq, Cornelia Handl, Oliver Pusch, Michael F Jantsch
Adenosine to inosine deamination of RNA is widespread in metazoa. Inosines are recognized as guanosines and, therefore, this RNA-editing can influence the coding potential, localization and stability of RNAs. Therefore, RNA editing contributes to the diversification of the transcriptome in a flexible manner. The editing reaction is performed by adenosine deaminases that act on RNA (ADARs), which are essential for normal life and development in many organisms. Changes in editing levels are observed during development but also in neurological pathologies like schizophrenia, depression or tumors...
February 2013: RNA Biology
Gilad Silberberg, Daniel Lundin, Ruth Navon, Marie Öhman
Schizophrenia and bipolar disorder (BPD) are common neurodevelopmental disorders, characterized by various life-crippling symptoms and high suicide rates. Multiple studies support a strong genetic involvement in the etiology of these disorders, although patterns of inheritance are variable and complex. Adenosine-to-inosine RNA editing is a cellular mechanism, which has been implicated in mental disorders and suicide. To examine the involvement of altered RNA editing in these disorders, we: (i) quantified the mRNA levels of the adenosine deaminase acting on RNA (ADAR) editing enzymes by real-time quantitative polymerase chain reaction, and (ii) measured the editing levels in transcripts of several neuroreceptors using 454 high-throughput sequencing, in dorsolateral-prefrontal cortices of schizophrenics, BPD patients and controls...
January 15, 2012: Human Molecular Genetics
Ali Ghaleiha, Navid Honarbakhsh, Mohammad-Ali Boroumand, Morteza Jafarinia, Mina Tabrizi, Farzin Rezaei, Maedeh Raznahan, Shahin Akhondzadeh
OBJECTIVE: It has been proposed that a deficit of adenosinergic activity could contribute to the pathophysiology of schizophrenia. The authors undertook this study to further evaluate the level of adenosine deaminase (ADA) in patients with chronic schizophrenia treated with monotherapy of haloperidol, risperidone or clozapine and correlation between the ADA level with response to treatment. METHODS: The trial was a prospective, 8-week, double blind study of parallel groups of patients with chronic schizophrenia...
March 2011: Human Psychopharmacology
Micah Simmons, James H Meador-Woodruff, Monsheel S Sodhi
RNA editing is a posttranscriptional process which critically modulates the function of several neurotransmitter receptors regulating mood, anxiety, learning, and memory. Data from several postmortem studies have shown increased 5-hydroxytryptamine-2C receptor RNA editing in mood disorders and suicide, and therefore the 5-hydroxytryptamine-2C receptor might be expected to have reduced signal transduction in these patients. In this study, we have tested the hypothesis that the expression levels of the enzymes which catalyze RNA editing, adenosine deaminase acting on RNA 1 (ADAR1) and ADAR2, are also abnormal in suicide...
October 27, 2010: Neuroreport
Gustavo Pimentel Dutra, Gustavo L Ottoni, Diogo R Lara, Maurício Reis Bogo
OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype...
September 2010: Revista Brasileira de Psiquiatria
Kazuya Iwamoto, Miki Bundo, Tadafumi Kato
Serotonin receptor 2C (HTR2C) is one of the attractive candidate genes for studying pathophysiology of mental disorders. Here we overviewed the genetic, expression and RNA editing studies suggesting the close relationship between HTR2C and major mental disorders including schizophrenia, bipolar disorder and major depression. We especially focused on the human studies as well as with reference to relevant cellular and animal models. Possible significance of genetic variations affecting expression and RNA editing and appropriate animal models that mimic human mental disorders were discussed...
July 2009: RNA Biology
Kazuya Iwamoto, Tadafumi Kato
A-to-I RNA editing has mainly been found in various receptors and ion channels in the central nervous system, including the serotonin 2C receptor, glutamate receptor, GABA receptor, and potassium channel. Interestingly, most of them are suggested to be involved in the pathophysiology of major mental disorders such as schizophrenia, bipolar disorder, and major depression. Here we review studies examining the relationship between the serotonin 2C receptor and major mental disorders.
April 2008: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Alessandro Barbon, Fabio Fumagalli, Luca La Via, Luca Caracciolo, Giorgio Racagni, Marco Andrea Riva, Sergio Barlati
Phencyclidine (PCP) induces a form of psychosis that mimics naturally occurring schizophrenia in the most relevant domains of the psychopathology. In this report, we investigated the effect of chronic treatment with PCP on expression and RNA editing of alpha-amino-propionic acid (AMPA) and kainate (KA) glutamate receptor (GluR), in the rat prefrontal cortex and the hippocampus. We found that chronic, but not acute, PCP treatment decreased GluRs expression in the rat prefrontal cortex but not in the hippocampus...
November 2007: Experimental Neurology
Birsen Ozyurt, Huseyin Ozyurt, Nusret Akpolat, Hasan Erdogan, Mustafa Sarsilmaz
MK-801 was shown to be one of the most neurotoxic non-competitive NMDA receptor antagonists. It is known that repeated injection of MK-801 was proposed in an animal model in psychosis. The aims of this study are to investigate the contributing effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Furthermore, there is evidence that oxygen free radicals play an important role in the pathophysiology of schizophrenia. In this study, Wistar Albino rats were divided into three groups: 1st group: Control, 2nd group: MK-801, 3rd group: MK-801+CAPE (Caffeic acid phenethyl ester) group...
May 9, 2007: Progress in Neuro-psychopharmacology & Biological Psychiatry
M G Brunstein, E M Silveira, L S Chaves, H Machado, O Schenkel, P Belmonte-de-Abreu, D O Souza, D R Lara
Adenosine is an important modulator of the nervous system that has been implicated in the pathophysiology of schizophrenia. We studied peripheral adenosine metabolism by determining the activity of serum adenosine deaminase, which converts adenosine into inosine, and 5'-nucleotidase, which converts AMP into adenosine, in 26 DSM-IV male schizophrenic patients under antipsychotic monotherapy and 26 healthy volunteers balanced for age and race. Schizophrenic patients treated either with typical antipsychotics or clozapine showed increased serum adenosine deaminase activity compared to controls (controls=18...
February 27, 2007: Neuroscience Letters
Mariela I Veggetti, Silvana De Lorenzo, Julieta J Cassone, Adriana S Losavio, Salomón Muchnik
OBJECTIVE: The diagnosis of bipolar disease frequently requires a long time since the age of onset, especially because the disease is misdiagnosed with schizophrenia. The aim of the present work was to investigate whether sera from bipolar patients have an active substance that allows making a fast identification of the disease. METHODS: Sera from healthy volunteers, euthymic and non-stabilized bipolar patients, and schizophrenic patients were passively transferred into CF1 mice and after 2 day injections, MEPP frequency from diaphragm muscles was recorded...
December 2006: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Birsen Ozyurt, Mustafa Sarsilmaz, Nusret Akpolat, Huseyin Ozyurt, Omer Akyol, Hasan Herken, Ilter Kus
The aims of this study are to investigate the contribution effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Because oxidative damage has been suggested in the neuropathophysiology of schizophrenia, the possible protecting agents against lipid peroxidation are potential target for the studies in this field. For this purpose, Wistar Albino rats were divided into three groups: the first group was used as control, MK-801 was given to the rats in the second group and MK-801+omega-3 essential fatty acids (EFA) was given to the third group...
January 2007: Neurochemistry International
Albert H C Wong, Barbara K Lipska, Olga Likhodi, Ernie Boffa, Daniel R Weinberger, James L Kennedy, Hubert H M Van Tol
Schizophrenia is a chronic, debilitating psychotic illness of unknown etiology that has been the subject of many genetic studies. We studied the neonatal ventral-hippocampal lesioned rat as an animal model of schizophrenia in order to identify novel candidate genes for schizophrenia. Temporal and frontal cortices were assessed using cDNA microarrays for differences in mRNA expression associated with the lesion, haloperidol treatment and in two rat strains with differential sensitivity to the behavioural effects of the lesion...
September 15, 2005: Schizophrenia Research
S D Detera-Wadleigh, C de Miguel, W H Berrettini, L E DeLisi, L R Goldin, E S Gershon
The restriction fragment length polymorphisms (RFLPs) associated with neuropeptide Y (NPY) and somatostatin loci were used to assess the possibility of linkage to a locus for affective disorder (AD). When somatostatin haplotypes were assigned to members of 2 AD pedigrees under either rare dominant or recessive transmission, the LOD scores obtained at 0% recombination were inconsistent with linkage. Similar results were obtained with NPY under rare dominant inheritance. Comparison of the frequency of the genotypes deduced from the polymorphic alleles of gastrin-releasing peptide, NPY, somatostatin and substance P in normals vs patients with either AD or schizophrenia suggests the absence of association...
1987: Journal of Psychiatric Research
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