Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder

Veldić, Marin; Kadriu, Bashkim; Maloku, Ekrem; Agís‐Balboa, Roberto Carlos; Guidotti, Alessandro; Davis, John M.; Costa, E.

doi:10.1016/j.schres.2006.11.029

Cited by 137 publications

(121 citation statements)

References 58 publications

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“…The gene encoding REELIN a protein involved in neuronal development and synaptogenesis, which is implicated in long-term memory was found to be methylated in brains of schizophrenia patients. The methylation of REELIN was correlated with its reduced expression and increased DNMT1 expression in GABAergic neurons in the prefrontal cortex Costa et al, 2002Costa et al, , 2003Grayson et al, 2005;Veldic et al, 2007].…”

Section: Epigenetic Plasticity and Late Onset Pathologymentioning

confidence: 98%

The social environment and the epigenome

Szyf

McGowan

Meaney

2007

Environ and Mol Mutagen

454

222

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The genome is programmed by the epigenome. Two of the fundamental components of the epigenome are chromatin structure and covalent modification of the DNA molecule itself by methylation. DNA methylation patterns are sculpted during development and it has been a long held belief that they remain stable after birth in somatic tissues. Recent data suggest that DNA methylation is dynamic later in life in postmitotic cells such as neurons and thus potentially responsive to different environmental stimuli throughout life. We hypothesize a mechanism linking the social environment early in life and long-term epigenetic programming of behavior and responsiveness to stress and health status later in life. We will also discuss the prospect that the epigenetic equilibrium remains responsive throughout life and that therefore environmental triggers could play a role in generating interindividual differences in human behavior later in life. We speculate that exposures to different environmental toxins alters long-established epigenetic programs in the brain as well as other tissues leading to lateonset disease. Environ. Mol. Mutagen. 49:46-60, 2008. V V C 2007 Wiley-Liss, Inc.

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Section: Epigenetic Plasticity and Late Onset Pathologymentioning

confidence: 98%

The social environment and the epigenome

Szyf

McGowan

Meaney

2007

Environ and Mol Mutagen

454

222

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“…RELN is expressed in Cajal-Retzius cells during early development and from many GABAergic cells in multiple cortical layers shortly after birth (Alcantara et al, 2006). Brain tissue from schizophrenic patients also consistently report decreased expression of the RELN gene Fatemi et al, 2000Fatemi et al, , 2001Folsom and Fatemi, 2013;Guidotti et al, 2000a;Habl et al, 2012;Impagnatiello et al, 1998;Maloku et al, 2010;Ruzicka et al, 2007), which is likely the result of altered genetic and/ or epigenetic regulation (Costa et al, 2003;Grayson et al, 2005Grayson et al, , 2006Tochigi et al, 2008;Veldic et al, 2004Veldic et al, , 2007. While the RELN deficiency observed in post-mortem tissue clearly does not impact cortical architecture to the same degree as total RELN loss during cortical development, it is likely that even a small reduction of RELN would affect synaptic integration during development and/or synaptic stability and plasticity in adulthood (Frotscher, 2010).…”

Section: Gene Effects Converge Onto Gaba System Developmentmentioning

confidence: 99%

“…In addition to being a necessary component of cortical development, RELN also has a role in stabilizing neurons and synapses throughout life (Abraham and Meyer, 2003;Frotscher, 2010;Guidotti et al, 2000b). It is expressed by GABAergic interneurons and the expression of the GAD1 and RELN genes is tightly coordinated by a common epigenetic mechanism (Costa et al, 2004;Grayson et al, 2005Grayson et al, , 2006Guidotti et al, 2000a;Impagnatiello et al, 1998;Kundakovic et al, 2009;Maloku et al, 2010;Noh et al, 2005;Pesold et al, 1999;Rodriguez et al, 2002;Ruzicka et al, 2007;Tochigi et al, 2008;Veldic et al, 2004Veldic et al, , 2007. In addition, rodent models show that RELN deficiency alone can result in downstream reductions of both GAD1 (Kutiyanawalla et al, 2012;Nullmeier et al, 2011;Pascual et al, 2004;Takayama, 1994) and BDNF (Pillai and Mahadik, 2008).…”

Section: Gene Effects Converge Onto Gaba System Developmentmentioning

confidence: 99%

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Schmidt

Mirnics

2014

Neuropsychopharmacol

189

130

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The origins of schizophrenia have eluded clinicians and researchers since Kraepelin and Bleuler began documenting their findings. However, large clinical research efforts in recent decades have identified numerous genetic and environmental risk factors for schizophrenia. The combined data strongly support the neurodevelopmental hypothesis of schizophrenia and underscore the importance of the common converging effects of diverse insults. In this review, we discuss the evidence that genetic and environmental risk factors that predispose to schizophrenia disrupt the development and normal functioning of the GABAergic system.

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“…One of the leading mechanisms for such enduring gene-environment interactions is that of epigenetic change, a series of biochemical mechanisms that can regulate gene expression by way of the opening and closing of chromatin structure. In some model systems, it seems that environmental conditions, in the form of chemical toxins or extreme physiological stress are sufficient to engage signal transduction cascades that induce either methylation of cytosine residues and/or the acetylation/de-acetylation of histone proteins in MSNs (Song et al, 2010;Veldic et al, 2007). Along chromosomal stretches in which DNA is highly methylated, it generally is less accessible for transcription and hence gene expression is reduced.…”

Section: Genes and Environmentmentioning

confidence: 99%

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Frank

Fossella

2010

Neuropsychopharmacol

171

167

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Many of the individual differences in cognition, motivation, and learningFand the disruption of these processes in neurological conditionsFare influenced by genetic factors. We provide an integrative synthesis across human and animal studies, focusing on a recent spate of evidence implicating a role for genes controlling dopaminergic function in frontostriatal circuitry, including COMT, DARPP-32, DAT1, DRD2, and DRD4. These genetic effects are interpreted within theoretical frameworks developed in the context of the broader cognitive and computational neuroscience literature, constrained by data from pharmacological, neuroimaging, electrophysiological, and patient studies. In this framework, genes modulate the efficacy of particular neural computations, and effects of genetic variation are revealed by assays designed to be maximally sensitive to these computations. We discuss the merits and caveats of this approach and outline a number of novel candidate genes of interest for future study.

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Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder

Cited by 137 publications

References 58 publications

The social environment and the epigenome

The social environment and the epigenome

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

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