Neuroepigenetics

What sets someone on a life trajectory? This question is at the heart of studies of 21st-century neurosciences that build on scientific models developed over the last 150 years that attempt to link psychopathology risk and human development. Historically, this research has documented persistent effects of singular, negative life experiences on people's subsequent development. More recently, studies have documented neuromolecular effects of early life adversity on life trajectories, resulting in models that frame lives as disproportionately affected by early negative experiences...

Vertebrate and invertebrate models of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, have been paramount to our understanding of the pathophysiology of these conditions; however, the brain epigenetic landscape is less well established in these disease models. DNA methylation, histone modifications, and microRNAs are among commonly studied mechanisms of epigenetic regulation. Genome-wide studies and candidate studies of specific methylation marks, histone marks, and microRNAs have demonstrated the dysregulation of these mechanisms in models of neurodegenerative diseases; however, the studies to date are scarce and inconclusive and the implications of many of these changes are still not fully understood...

For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life...

Brain functions are influenced by the presence, activity, and metabolism of the gut microbiota through the gut-microbiota-brain (GMB) axis. The consumption of a fiber-rich diet increases the content of short-chain fatty acids (SCFAs) from bacterial fermentation in the colon. Among SCFAs, butyrate stands out because of its wide array of biological functions, such as ability to influence brain functions. Pharmacologically, sodium butyrate (NaB) regulates gene expression in the brain, where it has several beneficial effects ranging from neurodegenerative diseases to behavioral disorders through inhibitors of histone deacetylases (HDACis)...

BACKGROUND: DNA methylation changes have known to downregulate several regulatory proteins epigenetically during various neurodegenerative disorders. Our study aims to understand the effect of this global DNA methylation on the cerebral complications of type 2 diabetes mice, and its notable effect on maintaining the synaptic fidelity. METHODS AND RESULTS: Chronic high fat diet and streptozotocin-induced diabetic mice were studied for the neurobehavioral and neuroanatomic parameters pertaining to prefrontal cortex, subsequently elucidating the associated changes in DNA methylation within these diabetic brains...

Chronic diabetic conditions have been associated with certain cerebral complications, that include neurobehavioral dysfunctional patterns and morphological alterations of neurons, especially the hippocampus. Neuroanatomical studies done by the authors have shown decreased total dendritic length, intersections, dendritic length per branch order and nodes in the CA1 hippocampal region of the diabetic brain as compared to its normal control group, indicating reduced dendritic arborization of the hippocampal CA1 neurons...

Anxiety is one of the most common psychiatric disorders diagnosed in the USA today. Like all mental illnesses, anxiety pathology includes genetic, molecular, somatic, and behavioral characteristics. Specific brain regions implicated in anxiety include the prefrontal cortex, amygdala, hippocampus, and hypothalamus. Together, these regions regulate fear-related learning and memory processes, and are innervated by neuronal projections that utilize glutamate and gamma-aminobutyric acid (GABA) as neurotransmitters...

The burgeoning field of neuroepigenetics has introduced chromatin modification as an important interface between experience and brain function. For example, epigenetic mechanisms like histone acetylation and DNA methylation operate throughout a lifetime to powerfully regulate gene expression in the brain that is required for experiences to be transformed into long-term memories. This Review highlights emerging evidence from sensory models of memory that converge on the premise that epigenetic regulation of activity-dependent transcription in the sensory brain facilitates highly precise memory recall...

Chromatin is organized into multiscale three-dimensional structures, including chromosome territories, A/B compartments, topologically associating domains, and chromatin loops. This hierarchically organized genomic architecture regulates gene transcription, which, in turn, is essential for various biological processes during brain development and adult plasticity. Here, we review different aspects of spatial genome organization and their functions in regulating gene expression in the nervous system, as well as their dysregulation in brain disorders...

Stress-induced neuroepigenetic programming gains growing more and more interest in the studies of the etiology of posttraumatic stress disorder (PTSD). However, seldom attention is focused on DNA demethylation in fear memory generalization, which is the core characteristic of PTSD. Here, we show that ten-eleven translocation protein 3 (TET3), the most abundant DNA demethylation enzyme of the TET family in neurons, senses environmental stress and bridges neuroplasticity with behavioral adaptation during fear generalization...

The growth arrest and DNA damage-inducible (Gadd) 45 proteins have been associated with numerous cellular mechanisms including cell cycle control, DNA damage sensation and repair, genotoxic stress, neoplasia, and molecular epigenetics. The genes were originally identified in in vitro screens of irradiation- and interleukin-induced transcription and have since been implicated in a host of normal and aberrant central nervous system processes. These include early and postnatal development, injury, cancer, memory, aging, and neurodegenerative and psychiatric disease states...

Epigenetic regulation of gene expression is necessary for maintaining higher-order cognitive functions (learning and memory). The current understanding of the role of epigenetics in the mechanism of Alzheimer's disease (AD) is focused on DNA methylation, chromatin remodeling, histone modifications, and regulation of non-coding RNAs. The pathogenetic links of this disease are the misfolding and aggregation of tau protein and amyloid peptides, mitochondrial dysfunction, oxidative stress, impaired energy metabolism, destruction of the blood-brain barrier, and neuroinflammation, all of which lead to impaired synaptic plasticity and memory loss...

No abstract text is available yet for this article.

Mutations in the PHIP/BRWD2 chromatin regulator cause the human neurodevelopmental disorder Chung-Jansen syndrome, while alterations in PHIP expression are linked to cancer. Precisely how PHIP functions in these contexts is not fully understood. Here we demonstrate that PHIP is a chromatin-associated CRL4 ubiquitin ligase substrate receptor and is required for CRL4 recruitment to chromatin. PHIP binds to chromatin through a trivalent reader domain consisting of a H3K4-methyl binding Tudor domain and two bromodomains (BD1 and BD2)...

Adolescence is a critical developmental period characterized by ongoing brain maturation processes including myelination and synaptic pruning. Adolescents experience heightened reward sensitivity, sensation seeking, impulsivity, and diminished inhibitory self-control, which contribute to increased participation in risky behaviors, including the initiation of alcohol use. Ethanol exposure in adolescence alters memory and cognition, anxiety-like behavior, and ethanol sensitivity as well as brain myelination and dendritic spine morphology, with effects lasting into adulthood...

The circadian rhythm of the human brain is attuned to sleep-wake cycles that entail global alterations in neuronal excitability. This periodicity involves a highly coordinated regulation of gene expression. A growing number of studies are documenting a fascinating connection between primate-specific retrotransposons (Alu elements) and key epigenetic regulatory processes in the primate brain. Collectively, these studies indicate that Alu elements embedded in the human neuronal genome mediate post-transcriptional processes that unite human-specific neuroepigenetic landscapes and circadian rhythm...

A key question in the rising field of neuroepigenetics is how behavioral plasticity is established and maintained in the developing CNS of multicellular organisms. Behavior is controlled through systemic changes in hormonal signaling, cell-specific regulation of gene expression, and changes in neuronal connections in the nervous system, however the link between these pathways is unclear. In the ant Camponotus floridanus, the epigenetic corepressor CoREST is a central player in experimentally-induced reprogramming of caste-specific behavior, from soldier (Major worker) to forager (Minor worker)...

The central dogma of molecular genetics is defined as encoded genetic information within DNA, transcribed into messenger RNA, which contain the instructions for protein synthesis, thus imparting cellular functionality and ultimately life. This molecular genetic theory has given birth to the field of neuroepigenetics, and it is now well established that epigenetic regulation of gene transcription is critical to the learning and memory process. In this review, we address a potential role for a relatively new player in the field of epigenetic crosstalk - long non-coding RNAs (lncRNAs)...

Neuroepigenetics, a new branch of epigenetics, plays an important role in the regulation of gene expression. Neuroepigenetics is associated with holistic neuronal function and helps in formation and maintenance of memory and learning processes. This includes neurodevelopment and neurodegenerative defects in which histone modification enzymes appear to play a crucial role. These modifications, carried out by acetyltransferases and deacetylases, regulate biologic and cellular processes such as apoptosis and autophagy, inflammatory response, mitochondrial dysfunction, cell-cycle progression and oxidative stress...

The circadian system interacts with the mesocorticolimbic reward system to modulate reward and memory in a time-of-day dependent manner. The circadian discrimination of reward, however, remains difficult to address between natural reinforcers and drugs of abuse. Circadian rhythms control cocaine sensitization and conversely cocaine causes long-term alteration in circadian periodicity in part through the serotonergic neurotransmission. Since neural circuits activated by cocaine and natural reinforcers do not completely overlap, we compared the effect of cocaine with that of sucrose, a strong reinforcer in rodents, by using passive chronic administration...