Prenatal MAM administration affects histone H3 methylation in postnatal life in the rat medial prefrontal cortex

Maćkowiak, Marzena; Bator, Ewelina; Latusz, Joachim; Mordalska, P.; Wędzony, K

doi:10.1016/j.euroneuro.2013.05.013

Cited by 45 publications

(36 citation statements)

References 48 publications

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“…For example, the GAD1(GAD67) GABA synthesis enzyme gene promoter shows in the SCZ cortex a shift from facilitative histone acetylation and H3K4 methylation toward repressive histone methylation markings [68,69]. Interestingly, such histone PTM changes have been reported in animals exposed to suboptimal postnatal care and parenting [70] or antimitotic drugs during prenatal development [71], which would be consistent with the neurodevelopmental hypothesis of schizophrenia. These findings may be relevant for future treatments of SCZ because, in the adult cerebral cortex, promoter-bound histone PTM at GAD1 and various other genes are altered after exposure to antipsychotic and mood-stabilizing drugs [69,[72][73][74].…”

Section: Histone Modificationssupporting

confidence: 66%

Epigenetic Dysregulation in the Schizophrenic Brain

Halene

Peter

Akbarian

2014

Curr Behav Neurosci Rep

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Schizophrenia (SCZ) is a severe psychiatric disorder, which lacks a unifying neuropathology. However, reproducible molecular alterations exist, including RNA expression changes affecting GABAergic and other neuronal signaling in cerebral cortex, myelination, and other cellular functions. Yet, for the large majority of RNAs altered in the SCZ brain, the underlying transcriptional and post-transcriptional diseaseassociated mechanisms remain unclear. Here, we provide an update on epigenetic regulators of gene expression that are potentially affected in some cases with SCZ, including DNA cytosine methylation, histone modifications and histone variants, and chromosomal loop formations facilitating longrange interactions of gene promoters with distal enhancer elements. Exploration of chromatin structure and function, in combination with transcriptome and genome sequencing, is likely to critically advance insight into the molecular mechanisms of disease in specific cases with SCZ.

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Section: Histone Modificationssupporting

confidence: 66%

Epigenetic Dysregulation in the Schizophrenic Brain

Halene

Peter

Akbarian

2014

Curr Behav Neurosci Rep

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“…Other studies have concluded that LSD1 may be primarily affecting H3K9 methylation, and not H3K4 methylation, in a developmentally regulated fashion in the prefrontal cortex (Maćkowiak et al, 2014). Our results seem to support this hypothesis in the amygdala, as H3K4me2 was not altered in AIE adult rats although Lsd1 mRNA and LSD1 protein were decreased.…”

Section: Discussionmentioning

confidence: 99%

Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood

et al. 2016

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Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during post-natal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1+8a (a neuron-specific splice variant) in specific amygdaloid structures compared to AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1+8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the Bdnf exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety.

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“…R. Soc. B 369: 20130514 [95]. Fifth, some drugs, including the atypical antipsychotic clozapine and the stimulant metamphetamine, alter H3K4 methylation signatures at specific gene promoters in cerebral cortex and striatum [12,96].…”

Section: Mouse Models For Genetic Disorders Associated With H3k4 Methmentioning

confidence: 99%

Regulation of histone H3K4 methylation in brain development and disease

Shen

Shulha

Weng

et al. 2014

Phil. Trans. R. Soc. B

122

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The growing list of mutations implicated in monogenic disorders of the developing brain includes at least seven genes ( ARX, CUL4B, KDM5A, KDM5C, KMT2A, KMT2C, KMT2D ) with loss-of-function mutations affecting proper regulation of histone H3 lysine 4 methylation, a chromatin mark which on a genome-wide scale is broadly associated with active gene expression, with its mono-, di- and trimethylated forms differentially enriched at promoter and enhancer and other regulatory sequences. In addition to these rare genetic syndromes, dysregulated H3K4 methylation could also play a role in the pathophysiology of some cases diagnosed with autism or schizophrenia, two conditions which on a genome-wide scale are associated with H3K4 methylation changes at hundreds of loci in a subject-specific manner. Importantly, the reported alterations for some of the diseased brain specimens included a widespread broadening of H3K4 methylation profiles at gene promoters, a process that could be regulated by the UpSET(KMT2E/MLL5)-histone deacetylase complex. Furthermore, preclinical studies identified maternal immune activation, parental care and monoaminergic drugs as environmental determinants for brain-specific H3K4 methylation. These novel insights into the epigenetic risk architectures of neurodevelopmental disease will be highly relevant for efforts aimed at improved prevention and treatment of autism and psychosis spectrum disorders.

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Prenatal MAM administration affects histone H3 methylation in postnatal life in the rat medial prefrontal cortex

Cited by 45 publications

References 48 publications

Epigenetic Dysregulation in the Schizophrenic Brain

Epigenetic Dysregulation in the Schizophrenic Brain

Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood

Regulation of histone H3K4 methylation in brain development and disease

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