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Antipsychotic response methylation

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https://www.readbyqxmd.com/read/27913254/quetiapine-treatment-reverses-depressive-like-behavior-and-reduces-dna-methyltransferase-activity-induced-by-maternal-deprivation
#1
Zuleide M Ignácio, Gislaine Z Réus, Helena M Abelaira, Amanda L Maciel, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Fernanda F Gava, Samira S Valvassori, André F Carvalho, João Quevedo
Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus...
November 29, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27793672/critical-involvement-of-the-orbitofrontal-cortex-in-hyperlocomotion-induced-by-nmda-receptor-blockade-in-mice
#2
Kaoru Seiriki, Atsushi Kasai, Takahiro Kuwaki, Takanobu Nakazawa, Shun Yamaguchi, Hitoshi Hashimoto
Glutamatergic N-methyl-d-aspartate (NMDA) receptors play critical roles in several neurological and psychiatric diseases. Blockade by noncompetitive NMDA receptor antagonist leads to psychotomimetic effects; however, the brain regions responsible for the effects are not well understood. Here, we determined the specific brain regions responsive to MK-801, a noncompetitive NMDA receptor antagonist, by mapping Arc expression as an indicator of neuronal activity using Arc::dVenus reporter mice. MK-801 increased dVenus expression predominantly in the orbitofrontal cortex (OFC) and, as expected, induced a marked hyperlocomotion...
October 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27577742/the-influence-of-the-cb1-receptor-ligands-on-the-schizophrenia-like-effects-in-mice-induced-by-mk-801
#3
Marta Kruk-Slomka, Barbara Budzynska, Tomasz Slomka, Izabela Banaszkiewicz, Grazyna Biala
A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders. For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms. The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia...
November 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27536115/cycloid-psychoses-in-the-psychosis-spectrum-evidence-for-biochemical-differences-with-schizophrenia
#4
Nora Wa van de Kerkhof, Durk Fekkes, Frank Mma van der Heijden, Witte Jg Hoogendijk, Gerald Stöber, Jos Im Egger, Willem Ma Verhoeven
Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27526039/progressive-supranuclear-palsy-and-corticobasal-degeneration-pathophysiology-and-treatment-options
#5
REVIEW
Ruth Lamb, Jonathan D Rohrer, Andrew J Lees, Huw R Morris
There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived...
September 2016: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/27471446/taurine-and-epidermal-growth-factor-belong-to-the-signature-of-first-episode-psychosis
#6
Kati Koido, Jürgen Innos, Liina Haring, Mihkel Zilmer, Aigar Ottas, Eero Vasar
This study evaluated the levels of two amino acid derivatives taurine and spermine in first-episode psychosis (FEP) patients and their response to antipsychotic treatment. The levels of taurine and spermine were significantly up-regulated in antipsychotic-naïve FEP patients compared to control subjects (CS). Treatment of FEP patients with antipsychotic drugs significantly reduced the positive symptoms of schizophrenia. This positive effect was accompanied by a significant reduction of taurine and spermine to the levels measured in CS...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27391101/persistent-gating-deficit-and-increased-sensitivity-to-nmda-receptor-antagonism-after-puberty-in-a-new-mouse-model-of-the-human-22q11-2-microdeletion-syndrome-a-study-in-male-mice
#7
Michael Didriksen, Kim Fejgin, Simon R O Nilsson, Michelle R Birknow, Hannah M Grayton, Peter H Larsen, Jes B Lauridsen, Vibeke Nielsen, Pau Celada, Noemi Santana, Pekka Kallunki, Kenneth V Christensen, Thomas M Werge, Tine B Stensbøl, Jan Egebjerg, Francois Gastambide, Francesc Artigas, Jesper F Bastlund, Jacob Nielsen
BACKGROUND: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. METHODS: We present a new mouse model (Df(h22q11)/+) of the deletion syndrome (22q11.2DS) and report on, to our knowledge, the most comprehensive study undertaken to date in 22q11.2DS models. The study was conducted in male mice...
July 7, 2016: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/27373856/neuropharmacological-efficacy-of-the-traditional-japanese-kampo-medicine-yokukansan-and-its-active-ingredients
#8
REVIEW
Yasushi Ikarashi, Kazushige Mizoguchi
Dementia is a progressive neurodegenerative disorder with cognitive dysfunction, and is often complicated by behavioral and psychological symptoms of dementia (BPSD) including excitement, aggression, and hallucinations. Typical and atypical antipsychotics are used for the treatment of BPSD, but induce adverse events. The traditional Japanese Kampo medicine yokukansan (YKS), which had been originated from the traditional Chinese medicine Yi-Gan-San, has been reported to improve BPSD without severe adverse effects...
October 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27296677/n-n-dimethylglycine-differentially-modulates-psychotomimetic-and-antidepressant-like-effects-of-ketamine-in-mice
#9
Jen-Cheng Lin, Ming-Huan Chan, Mei-Yi Lee, Yi-Chyan Chen, Hwei-Hsien Chen
Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/26876050/genetic-association-analysis-of-n-methyl-d-aspartate-receptor-subunit-gene-grin2b-and-clinical-response-to-clozapine
#10
Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Jo Knight, Gary Remington, Daniel J Müller, James L Kennedy
OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-d-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine...
March 2016: Human Psychopharmacology
https://www.readbyqxmd.com/read/26756904/behavioral-and-molecular-neuroepigenetic-alterations-in-prenatally-stressed-mice-relevance-for-the-study-of-chromatin-remodeling-properties-of-antipsychotic-drugs
#11
E Dong, P Tueting, F Matrisciano, D R Grayson, A Guidotti
We have recently reported that mice born from dams stressed during pregnancy (PRS mice), in adulthood, have behavioral deficits reminiscent of behaviors observed in schizophrenia (SZ) and bipolar (BP) disorder patients. Furthermore, we have shown that the frontal cortex (FC) and hippocampus of adult PRS mice, like that of postmortem chronic SZ patients, are characterized by increases in DNA-methyltransferase 1 (DNMT1), ten-eleven methylcytosine dioxygenase 1 (TET1) and exhibit an enrichment of 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) at neocortical GABAergic and glutamatergic gene promoters...
January 12, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/26558619/serotonin-5-ht-1a-receptor-agonism-and-5-ht7-receptor-antagonism-ameliorate-the-subchronic-phencyclidine-induced-deficit-in-executive-functioning-in-mice
#12
Lakshmi Rajagopal, Bill W Massey, Eric Michael, Herbert Y Meltzer
RATIONALE: Reversal learning (RL), a type of executive function, dependent on prefrontal cortical function, is impaired in rodents by subchronic (sc) treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), a widely studied model of cognitive impairment in schizophrenia (CIS). OBJECTIVE: The principal objective of this study was to determine the ability of serotonin (5-HT)1A partial agonism and 5-HT7 receptor antagonism to improve RL in scPCP-treated mice...
February 2016: Psychopharmacology
https://www.readbyqxmd.com/read/26232639/positive-allosteric-modulators-of-alpha-7-nicotinic-acetylcholine-receptors-reverse-ketamine-induced-schizophrenia-like-deficits-in-rats
#13
Agnieszka Nikiforuk, Tomasz Kos, Małgorzata Hołuj, Agnieszka Potasiewicz, Piotr Popik
Alpha 7 nicotinic acetylcholine receptors (α7-nAChRs) have generated great interest as targets of new pharmacological treatments for cognitive dysfunction in schizophrenia. One promising recent approach is based on the use of positive allosteric modulators (PAMs) of α7-nAChRs, which demonstrate several advantages over direct agonists. Nevertheless, the efficacy of these newly introduced α7-nAChR agents has not been extensively characterised in animal models of schizophrenia. The aim of the present study was to evaluate the efficacy of type I and II PAMs, N-(5-chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)urea (PNU-120596) and N-(4-chlorophenyl)-[[(4-chlorophenyl)amino]methylene]-3-methyl-5-isoxazoleacet-amide (CCMI), respectively, and galantamine, an acetylcholinesterase inhibitor (AChE) that also allosterically modulates nAChRs, against ketamine-induced cognitive deficits and social withdrawal in rats...
February 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26216995/action-potentials-and-amphetamine-release-antipsychotic-drug-from-dopamine-neuron-synaptic-vmat-vesicles
#14
Kristal R Tucker, Ethan R Block, Edwin S Levitan
Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients...
August 11, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26214776/olanzapine-inhibits-the-proliferation-and-induces-the-differentiation-of-glioma-stem-like-cells-through-modulating-the-wnt-signaling-pathway-in-vitro
#15
Q-H Guo, H-J Yang, S-D Wang
OBJECTIVE: Olanzapine, a D2/5-HT2 antagonist, is often used as an atypical antipsychotic drug in clinical. Previous research has found its new pharmacological influence on enhancing the differentiation of neural stem cells (NSCs) to oligodendrocyte-like cells (ODLCs). Glioblastomas are associated with poor prognoses owing to the glioma stem-like cells (GSLCs), which have a great many of similarities with adult NSCs. Hence, in this article, we aim to study the effects and associated mechanisms of olanzapine on GSLCs derived from human U87MG glioblastoma cell lines...
July 2015: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/26137221/insights-into-the-origin-of-dna-methylation-differences-between-monozygotic-twins-discordant-for-schizophrenia
#16
Melkaye G Melka, Christina A Castellani, Richard O'Reilly, Shiva M Singh
BACKGROUND: DNA methylation differences between monozygotic twins discordant for schizophrenia have been previously reported. However, the origin of methylation differences between monozygotic twins discordant for schizophrenia is not clear. The findings here argue that all DNA methylation differences may not necessarily represent the cause of the disease; rather some may result from the effect of antipsychotics. METHODS: Methylation differences in rat brain regions and also in two pairs of unrelated monozygotic twins discordant for schizophrenia have been studied using genome-wide DNA methylation arrays at Arraystar Inc...
2015: Journal of Molecular Psychiatry
https://www.readbyqxmd.com/read/26120009/epigenetic-signaling-in-schizophrenia
#17
REVIEW
Daisuke Ibi, Javier González-Maeso
Histone modifications and DNA methylation represent central dynamic and reversible processes that regulate gene expression and contribute to cellular phenotypes. These epigenetic marks have been shown to play fundamental roles in a diverse set of signaling and behavioral outcomes. Psychiatric disorders such as schizophrenia and depression are complex and heterogeneous diseases with multiple and independent factors that may contribute to their pathophysiology, making challenging to find a link between specific elements and the underlying mechanisms responsible for the disorder and its treatment...
October 2015: Cellular Signalling
https://www.readbyqxmd.com/read/26052791/attenuation-of-mk-801-induced-behavioral-perseveration-by-typical-and-atypical-antipsychotic-pretreatment-in-rats
#18
Erin W Tuplin, Marlaina R Stocco, Matthew R Holahan
The noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-10-imine maleate (MK-801) has been shown to increase the probability of operant responding during extinction and reduce infralimbic prefrontal cortical activation, possibly modeling the cognitive dysfunction symptomology, and underlying cause, in patients with schizophrenia. The present study sought to determine if typical and/or atypical antipsychotics would attenuate the MK-801-induced behavioral perseveration and whether this would be associated with concomitant changes in phosphorylated ERK1/2 (pERK1/2) labeling in the infralimbic cortex (IL)...
August 2015: Behavioral Neuroscience
https://www.readbyqxmd.com/read/26019538/whole-genome-methylation-analyses-of-schizophrenia-patients-before-and-after-treatment
#19
Blaga Rukova, Rada Staneva, Savina Hadjidekova, Georgi Stamenov, Vihra Milanova, Draga Toncheva
The aetiology of schizophrenia is still unknown but it involves both heritable and non-heritable factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. It takes part in the regulation of neurodevelopment and may be a contributing factor to the pathogenesis of brain diseases. It was found that many of the antipsychotic drugs may lead to epigenetic modifications. We have performed 42 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands...
May 4, 2014: Biotechnology, Biotechnological Equipment
https://www.readbyqxmd.com/read/25991655/a-methionine-induced-animal-model-of-schizophrenia-face-and-predictive-validity
#20
Lien Wang, Amal Alachkar, Nayna Sanathara, James D Belluzzi, Zhiwei Wang, Olivier Civelli
BACKGROUND: Modulating the methylation process induces broad biochemical changes, some of which may be involved in schizophrenia. Methylation is in particular central to epigenesis, which is also recognized as a factor in the etiology of schizophrenia. Because methionine administration to patients with schizophrenia has been reported to exacerbate their psychotic symptoms and because mice treated with methionine exhibited social deficits and prepulse inhibition impairment, we investigated whether methionine administration could lead to behavioral changes that reflect schizophrenic symptoms in mice...
November 2015: International Journal of Neuropsychopharmacology
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