Epigenetics, microRNA, and addiction.
Authors: Kenny PJ Abstract Drug addiction is characterized by uncontrolled drug consumption and high rates of relapse to drug taking during periods of attempted abstinence. Addiction is now largely considered a disorder of experience-dependent neuroplasticity, driven by remodeling of synapses in reward and motivation relevant brain circuits in response to a history of prolonged drug intake. Alterations in gene expression play a central role in addiction-relevant neuroplasticity, but the mechanisms by which additive drugs remodel brain motivation circuits remains unclear. MicroRNAs (miRNAs) are a class of noncoding ...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

New approaches to manipulating the epigenome.
Authors: Day JJ Abstract Cellular processes that control transcription of genetic information are critical for cellular function, and are often implicated in psychiatric and neurological disease states. Among the most critical of these processes are epigenetic mechanisms, which serve to link the cellular environment with genomic material. Until recently our understanding of epigenetic mechanisms has been limited by the lack of tools that can selectively manipulate the epigenome with genetic, cellular, and temporal precision, which in turn diminishes the potential impact of epigenetic processes as therapeutic target...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

Role of DNA methylation and the DNA methyltransferases in learning and memory.
Authors: Morris MJ, Monteggia LM Abstract Dynamic regulation of chromatin structure in postmitotic neurons plays an important role in learning and memory. Methylation of cytosine nucleotides has historically been considered the strongest and least modifiable of epigenetic marks. Accumulating recent data suggest that rapid and dynamic methylation and demethylation of specific genes in the brain may play a fundamental role in learning, memory formation, and behavioral plasticity. The current review focuses on the emergence of data that support the role of DNA methylation and demethylation, and its molecular mediators...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

The epigenetic dimension of Alzheimer's disease: causal, consequence, or curiosity?
In conclusion, epigenetic mechanisms are broadly deregulated in AD mainly upstream, but also downstream, of key pathophysiological processes. While some epigenetic shifts oppose the evolution of AD, most appear to drive its progression. Epigenetic changes are of irrefutable importance for AD, but they await further elucidation from the perspectives of pathogenesis, biomarkers and potential treatment. PMID: 25364287 [PubMed - in process] (Source: Dialogues in Clinical Neuroscience)
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

Epigenetic alterations in depression and antidepressant treatment.
Authors: Menke A, Binder EB Abstract Epigenetic modifications control chromatin structure and function, and thus mediate changes in gene expression, ultimately influencing protein levels. Recent research indicates that environmental events can induce epigenetic changes and, by this, contribute to long-term changes in neural circuits and endocrine systems associated with altered risk for stress-related psychiatric disorders such as major depression. In this review, we describe recent approaches investigating epigenetic modifications associated with altered risk for major depression or response to antidepressant drug...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

Epigenetic mechanisms in schizophrenia.
Authors: Akbarian S Abstract Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DMA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clu...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

DNA methylation and demethylation as targets for antipsychotic therapy.
Authors: Guidotti A, Grayson DR Abstract Schizophrenia (SZ) and bipolar disorder (BPD) patients show a downregulation of GAD67, reelin (RELN), brain-derived neurotrophic factor (BDNF), and other genes expressed in telencephalic GABAergic and glutamatergic neurons. This downregulation is associated with the enrichment of 5-methylcytosine and 5-hydroxymethylcytosine proximally at gene regulatory domains at the respective genes. A pharmacological strategy to reduce promoter hypermethylation and to induce a more permissive chromatin conformation is to administer drugs, such as the histone deacetylase (HDAC) inhibitor v...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research

Increased DNA methylation in the suicide brain.
Authors: Haghighi F, Xin Y, Chanrion B, O'Donnell AH, Ge Y, Dwork AJ, Arango V, Mann JJ Abstract Clinical studies find that childhood adversity and stress-ful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides ...
Source: Dialogues in Clinical Neuroscience - November 12, 2014 Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research