“…Although several components of the diet can mediate this effect, an association between vitamin B12 and folic acid supplementation in the mother’s diet during pregnancy and defects on the myelination in the nervous system of offspring has been described [23]. In a similar manner, the negative effect of fetal exposure to factors such as tobacco, alcohol consumption, stress or infections had also been investigated in the context of risk to neurological disorders in the offspring [24–26]. How epigenetics modulate changes in brain development and functions even across generations (the named “transgenerational inheritance”) will be the subject of future research in the field and surely will contribute to improve strategies supporting healthy development.Fig.…”
Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation. The reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets. Rather than providing a broad description of the pathways epigenetically deregulated in human neurological disorders, in this review, we have focused on the potential use of epigenetic enzymes as druggable targets to ameliorate neural decline during normal ageing and especially in neurological disorders. We will firstly discuss recent progress that supports a key role of epigenetic regulation during healthy ageing with an emphasis on the role of epigenetic regulation in adult neurogenesis. Then, we will focus on epigenetic alterations associated with ageing-related human disorders of the central nervous system. We will discuss examples in the context of psychiatric disorders, including schizophrenia and posttraumatic stress disorders, and also dementia or Alzheimer’s disease as the most frequent neurodegenerative disease. Finally, methodological limitations and future perspectives are discussed.
“…Although several components of the diet can mediate this effect, an association between vitamin B12 and folic acid supplementation in the mother’s diet during pregnancy and defects on the myelination in the nervous system of offspring has been described [23]. In a similar manner, the negative effect of fetal exposure to factors such as tobacco, alcohol consumption, stress or infections had also been investigated in the context of risk to neurological disorders in the offspring [24–26]. How epigenetics modulate changes in brain development and functions even across generations (the named “transgenerational inheritance”) will be the subject of future research in the field and surely will contribute to improve strategies supporting healthy development.Fig.…”
Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation. The reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets. Rather than providing a broad description of the pathways epigenetically deregulated in human neurological disorders, in this review, we have focused on the potential use of epigenetic enzymes as druggable targets to ameliorate neural decline during normal ageing and especially in neurological disorders. We will firstly discuss recent progress that supports a key role of epigenetic regulation during healthy ageing with an emphasis on the role of epigenetic regulation in adult neurogenesis. Then, we will focus on epigenetic alterations associated with ageing-related human disorders of the central nervous system. We will discuss examples in the context of psychiatric disorders, including schizophrenia and posttraumatic stress disorders, and also dementia or Alzheimer’s disease as the most frequent neurodegenerative disease. Finally, methodological limitations and future perspectives are discussed.
“…Epigenetic changes take place during brain development and are also the result of drug exposure, including alcohol (Krishnan, Sakharkar, Teppen, Berkel, & Pandey, ; Renthal & Nestler, ). Recent experimental studies have indicated that alcohol consumption induces epigenetic inheritance through the male germ line (Rachdaoui & Sarkar, ). Indeed, different studies support the contribution of epigenetic modifications (e.g., histone acetylation/deacetylation) in the long‐lasting changes induced by ethanol abuse in adolescence (Montesinos, Pascual, Rodriguez‐Arias, et al, ; Sakharkar et al, ).…”
Section: Animal Studies and Mechanisms Of Ethanol Action In The Adolementioning
confidence: 99%
“…Epigenetic changes take place during brain development and are also the result of drug exposure, including alcohol (Krishnan, Sakharkar, Teppen, Berkel, & Pandey, 2014;Renthal & Nestler, 2008). Recent experimental studies have indicated that alcohol consumption induces epigenetic inheritance through the male germ line (Rachdaoui & Sarkar, 2014). Indeed, different studies support the PASCUAL ET AL.…”
Section: A N I M Al S Tu D I Es a Nd M Ec Ha N I S M S Of E Th An Omentioning
Adolescence is a critical stage of brain maturation in which important plastic and dynamic processes take place in different brain regions, leading to development of the adult brain. Ethanol drinking in adolescence disrupts brain plasticity and causes structural and functional changes in immature brain areas (prefrontal cortex, limbic system) that result in cognitive and behavioral deficits. These changes, along with secretion of sexual and stress-related hormones in adolescence, may impact self-control, decision making, and risk-taking behaviors that contribute to anxiety and initiation of alcohol consumption. New data support the participation of the neuroimmune system in the effects of ethanol on the developing and adult brain. This article reviews the potential pathological bases that underlie the effects of alcohol on the adolescent brain, such as the contribution of genetic background, the perturbation of epigenetic programming, and the influence of the neuroimmune response. Special emphasis is given to the actions of ethanol in the innate immune receptor toll-like receptor 4 (TLR4), since recent studies have demonstrated that by activating the inflammatory TLR4/NFκB signaling response in glial cells, binge drinking of ethanol triggers the release of cytokines/chemokines and free radicals, which exacerbate the immune response that causes neuroinflammation/neural damage as well as short- and long-term neurophysiological, cognitive, and behavioral dysfunction. Finally, potential treatments that target the neuroimmune response to treat the neuropathological and behavioral consequences of adolescent alcohol abuse are discussed.
“…For example, low maternal licking and grooming of pups during the early postnatal period led to somatic epigenetic modifications that were associated with stress intolerance and were maintained in the adult female offspring ( F 1 mother) which in turn perpetuated the phenotype of low licking and grooming to the next generation of mothers ( F 2). Adapted from Rachdaoui & Sarkar ()…”
Alcohol exposure during fetal and early postnatal development can lead to an increased incidence of later life adult-onset diseases. Examples include central nervous system dysfunction, depression, anxiety, hyperactivity, and an inability to deal with stressful situations, increased infection and cancer. Direct effects of alcohol leading to developmental abnormalities often involve epigenetic modifications of genes that regulate cellular functions. Epigenetic marks carried over from the parents are known to undergo molecular programming events that happen early in embryonic development by a wave of DNA demethylation, which leaves the embryo with a fresh genomic composition. The proopiomelanocortin (Pomc) gene controls neuroendocrine-immune functions and is imprinted by fetal alcohol exposure. Recently, this gene has been shown to be hypermethylated through three generations. Additionally, the alcohol epigenetic marks on the Pomc gene are maintained in the male but not in the female germline during this transgenerational transmission. These data suggest that the male-specific chromosome might be involved in transmitting alcohol epigenetic marks through multiple generations.
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