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      Epigenetic and transgenerational reprogramming of brain development.

      Author(s): 1
      Publication date (Electronic):
      Journal: Nature reviews. Neuroscience

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          Abstract

          Neurodevelopmental programming - the implementation of the genetic and epigenetic blueprints that guide and coordinate normal brain development - requires tight regulation of transcriptional processes. During prenatal and postnatal time periods, epigenetic processes fine-tune neurodevelopment towards an end product that determines how an organism interacts with and responds to exposures and experiences throughout life. Epigenetic processes also have the ability to reprogramme the epigenome in response to environmental challenges, such as maternal stress, making the organism more or less adaptive depending on the future challenges presented. Epigenetic marks generated within germ cells as a result of environmental influences throughout life can also shape future generations long before conception occurs.

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          Most cited references175

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          Epigenetic programming by maternal behavior.

          Ian Weaver, Nadia Cervoni, Frances Champagne … (2004)
          Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.
          Article 0 comments Cited 1322 times – based on 0 reviews     Review now
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            Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.

            John F. Cryan, Timothy Dinan (2012)
            Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS--possibly through neural, endocrine and immune pathways--and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
            Article 0 comments Cited 870 times – based on 0 reviews     Review now
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              Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.

              D. Liu, J Diorio, B Tannenbaum … (1997)
              Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.
              Article 0 comments Cited 423 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Nat. Rev. Neurosci.
                Title: Nature reviews. Neuroscience
                ISSN (Electronic): 1471-0048
                ISSN (Print): 1471-003X
                Publication date (Electronic): Jun 2015
                Volume: 16
                Issue: 6
                Affiliations
                [1 ] Department of Biomedical Sciences, School of Veterinary Medicine and Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
                Article
                Publisher Item ID: nrn3818
                DOI: 10.1038/nrn3818
                PubMed ID: 25921815
                SO-VID: 09f06231-94c7-4e6a-a93d-03a7890a7646
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