Valproic acid (VPA) reduces sensorimotor gating deficits and HDAC2 overexpression in the MAM animal model of schizophrenia

Bator, Ewelina; Latusz, Joachim; Radaszkiewicz, Aleksandra; Wędzony, K; Mackowiak, M.

doi:10.1016/j.pharep.2015.04.004

Cited by 19 publications

(14 citation statements)

References 31 publications

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“…Thirty-eight articles met all the inclusion criteria; studies retrieved for the review were organized in a flow diagram ( Figure 2). Twenty-one described studies of rodent samples (Tremolizzo et al, 2002;Dong et al, 2005;Tremolizzo et al, 2005;Kim et al, 2008;Dong et al, 2010;Hobara et al, 2010;Perisic et al, 2010;Matrisciano et al, 2011;Wang et al, 2012;Zimmermann et al, 2012;Calabrese et al, 2013;Leng et al, 2013;Ookubo et al, 2013;Liu et al, 2014;Mackowiak et al, 2014;Balasubramanian et al, 2015;Bator et al, 2015;Dwivedi and Zhang, 2015;Lee et al, 2015;Leng et al, 2016;Bahna and Niles, 2017). Seven articles studied human cell lines (Asai et al, 2013;Kao et al, 2013;Dyrvig et al, 2017;Zong et al, 2017;Billingsley et al, 2018;Dyrvig et al, 2019;Manca et al, 2019) and eight focused on blood samples of subjects diagnosed with either of the selected psychiatric disorders (Gavin et al, 2009;D'Addario et al, 2012;Dell'Osso et al, 2014;Huzayyin et al, 2014;Burghardt et al, 2015;Burghardt et al, 2016;Houtepen et al, 2016;Bengesser et al, 2018).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…In primary glia VPA dose-dependently increased FGF21 mRNA levels. (Bator et al, 2015) Explore the effect of VPA on histone acetylation in a neurodevelopmental animal model of schizophrenia.…”

Section: Fgf21mentioning

confidence: 99%

“…Both VPA and antipsychotics have shown a potential reversibility effect of symptoms and epigenetic markers on MET or MAM treated rodents (Tremolizzo et al, 2002;Lodge, 2013;Wang et al, 2015). Five papers examined the impact of mood stabilizers on genes involved in the regulation of histone activity (Kim et al, 2008;Hobara et al, 2010;Ookubo et al, 2013;Mackowiak et al, 2014;Bator et al, 2015). Kim et al (Kim et al, 2008) exposed rat C6 glioma cells to prolonged treatment with low clinically relevant doses of VPA (0.5 mM or 1 mM), reporting significant increases in HDAC-1, -2, and -3 mRNA expression (class I HDAC isoforms), as well as increases in methyl-CpG binding protein 2 (MeCP2) and Metallothionein-1M (MT 1 ) mRNA expression.…”

Section: Mouse Frontal Cortexmentioning

confidence: 99%

“…Use of VPA in early adolescence prevented disturbances in ASH2L and H3K4me3 but did not affect the levels of JARID1c, a key protein in the demethylase activity on H3K4me3 (Mackowiak et al, 2014;Rondinelli et al, 2015). The same group reported that VPA prevented an increase in HDAC-2 levels evoked by MAM but not H3K9 acetylation levels (Bator et al, 2015). An additional paper studied the impact of CBZ and VPA on DNMT1 activity in primary astrocytes from rat cortex, reporting that neither of the agents altered the expression levels of DNMT (Zimmermann et al, 2012).…”

Section: Mouse Frontal Cortexmentioning

confidence: 99%

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Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review

et al. 2020

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Background: Epimutations secondary to gene-environment interactions have a key role in the pathophysiology of major psychiatric disorders. In vivo and in vitro evidence suggest that mood stabilizers can potentially reverse epigenetic deregulations found in patients with schizophrenia or mood disorders through mechanisms that are not yet fully understood. However, their activity on epigenetic processes has made them a research target for therapeutic approaches. Methods:We conducted a comprehensive literature search of PubMed and EMBASE for studies investigating the specific epigenetic changes induced by non-antipsychotic mood stabilizers (valproate, lithium, lamotrigine, and carbamazepine) in animal models, human cell lines, or patients with schizophrenia, bipolar disorder, or major depressive disorder. Each paper was reviewed for the nature of research, the species and tissue examined, sample size, mood stabilizer, targeted gene, epigenetic changes found, and associated psychiatric disorder. Every article was appraised for quality using a modified published process and those who met a quality score of moderate or high were included.Results: A total of 2,429 records were identified; 1,956 records remained after duplicates were removed and were screened via title, abstract and keywords; 129 records were selected for full-text screening and a remaining of 38 articles were included in the qualitative synthesis. Valproate and lithium were found to induce broader epigenetic changes through different mechanisms, mainly DNA demethylation and histones acetylation. There was less literature and hence smaller effects attributable to lamotrigine and carbamazepine could be associated overall with the small number of studies on these agents. Findings were congruent across sample types.Conclusions: An advanced understanding of the specific epigenetic changes induced by classic mood stabilizers in patients with major psychiatric disorders will facilitate Frontiers in Pharmacology | www.frontiersin.org

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Section: Study Selection and Characteristicsmentioning

confidence: 99%

Section: Fgf21mentioning

confidence: 99%

Section: Mouse Frontal Cortexmentioning

confidence: 99%

Section: Mouse Frontal Cortexmentioning

confidence: 99%

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Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review

et al. 2020

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“…VPA may also be beneficial in the treatment of schizophrenia [Johannessen, 2000;Benes and Berretta, 2001;Guidotti et al, 2005;Bator et al, 2015;Pang et al, 2016]. One mechanism for the action of VPA is increasing GABAergic neurotransmission by inhibiting GABA transaminase, which is responsible for synthesis and degradation of GABA [Johannessen, 2000].…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Epigenetic Mechanisms in Psychiatric Diseases and Epigenetic Therapy

Karslı-Çeppioğlu

2016

Drug Development Research

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Preclinical Research Epigenetic mechanisms refer covalent modification of DNA and histone proteins that control transcriptional regulation of gene expression. Epigenetic regulation is involved in the development of the nervous system and plays an important role in the pathophysiology of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Epigenetic drugs, including histone deacetylation and DNA methylation inhibitors have received increased attention for the management of psychiatric diseases. The purpose of this review is to discuss the potential of epigenetic drugs to treat these disorders and to clarify the mechanisms by which they regulate the dysfunctional genes in the brain. Drug Dev Res 77 : 407-413, 2016. © 2016 Wiley Periodicals, Inc.

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Adolescent Social Isolation Affects Schizophrenia-Like Behavior in the MAM-E17 Model of Schizophrenia

et al. 2018

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Social isolation (SI) during adolescence may induce schizophrenia-like behavior. In the present study, we investigated whether adolescent SI might affect the development of schizophrenia-like behavior in the MAM-E17 neurodevelopmental model of schizophrenia. Rats were socially isolated for 10 days during adolescence (postnatal days (P) 30-40), followed by resocialization until late adolescence (P45-P48) or early adulthood (P70-P75); behavioral and neurochemical studies were performed at these ages. The behavioral studies analyzed locomotor activity, social interaction, recognition memory, and sensorimotor gating; GAD65 and GAD67 protein levels were measured in the prefrontal cortex. The results showed that SI did not affect locomotor activity, but it prevented the social interaction deficits induced by MAM administration at both of the analyzed age points. However, SI induced a deficit in recognition memory in the MAM group during adolescence, which was not observed in the MAM-treated, socially housed rats at this age. In adulthood, impairments in recognition memory were detected in both MAM groups. In contrast, SI did not accelerate the appearance of sensorimotor gating deficits in MAM animals during adolescence, and sensorimotor gating impairments were observed in both MAM groups during adulthood. Adolescent SI rearing did not affect any examined behavioral responses in the VEH-treated groups. SI altered the levels of GAD65 and GAD67 proteins during adolescence in both groups; however, the decrease in the level of GAD65 protein was observed only in the adult MAM-SI group. Thus, SI rearing during a defined period of adolescence might have specific effects on the emergence of schizophrenia-like abnormalities in MAM-treated animals.

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Valproic acid (VPA) reduces sensorimotor gating deficits and HDAC2 overexpression in the MAM animal model of schizophrenia

Cited by 19 publications

References 31 publications

Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review

Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review

Epigenetic Mechanisms in Psychiatric Diseases and Epigenetic Therapy

Adolescent Social Isolation Affects Schizophrenia-Like Behavior in the MAM-E17 Model of Schizophrenia

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