Tuesday, 5 March 2013

Maternal stress induces epigenetic signatures of neurological diseases in the offspring

#MSBlog: Who knows what epigenetics is? It is relevant to MS!


Epub: Zucchi et al. Maternal stress induces epigenetic signatures of psychiatric and neurological diseases in the offspring. PLoS One. 2013;8(2):e56967. doi: 10.1371/journal.pone.0056967.

Background: The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through microRNA (miRNA) regulation, responds to prenatal stress in association with epigenetic signatures of psychiatric and neurological diseases. 


Methods: Pregnant Long-Evans rats were assigned to stress from gestational days 12 to 18 while others served as handled controls. 

Results: Gestational stress in the dam disrupted parturient maternal behaviour and was accompanied by characteristic brain miRNA profiles in the mother and her offspring, and altered transcriptomic brain profiles in the offspring. In the offspring brains, prenatal stress upregulated miR-103, which is involved in brain pathologies, and downregulated its potential gene target . Prenatal stress downregulated miR-145, a marker of multiple sclerosis in humans. Prenatal stress also upregulated miR-323 and miR-98, which may alter inflammatory responses in the brain. Furthermore, prenatal stress upregulated miR-219, which targets the gene . Both miR-219 and are putative markers of schizophrenia and bipolar affective disorder in humans. Offspring transcriptomic changes included genes related to development, axonal guidance and neuropathology. 

Conclusion: These findings indicate that prenatal stress modifies epigenetic signatures linked to disease during critical periods of fetal brain development. These observations provide a new mechanistic association between environmental and genetic risk factors in psychiatric and neurological disease.

"This study is quite complex. In a nutshell stress during pregnancy, particularly during critical periods of brain development, affects how the brain functions and potentially predispose it to develop disease in the future, for example MS."
"This is done via epigenetics; a big word for how the environment, in this case a stressful environment imprints and programs the cells of the brain to behave and react in the future. The field of epigentics is well developed and is emerging as a major factor in population health. The best know example is in utero stress due to starvation. Severe calorie restriction in the womb predisposes you to develop obesity, diabetes and hypertension as an adult and to pass this trait onto the next generation. Wow! How does this happen? It happens by imprinting or altering  the structure of your DNA; enzymes stick molecules (methyl and acetyl groups) onto your DNA or DNA-binding proteins that then affect how the DNA is read and handled in the future."

"What evidence is there that epigenetics is playing a role in MS? Firstly, if you mother had MS your are more than twice as likely to get the MS compared to if your father had MS. Non-identical twins are more likely to be concordant for MS   (~6.5%) , i.e. both have the disease, compared to straight siblings (~2.5%); this is clearly not due to simple genetics as genetic sharing in these two situations are the same. The increased risk can only be explained by sharing the womb or early environment together. Finally, there is the month of birth effect; your chances of getting MS are higher if your mother was pregnant through winter compared to if she was pregnant in summer. This all tells us  that something must be acting via a pathway that affects how your genome functions and is not due to actual DNA code or sequence. What is interesting is that epigenetic signatures can be passed on from one generation to the next generation. And you thought biology was easy!" 


A microRNA (abbr. miRNA) is a small non-coding RNA molecule (ca. 22 nucleotides) found in plants and animals, which functions in transcriptional and post-transcriptional regulation of gene expression.  miRNAs function via base-pairing with complementary sequences within mRNA molecules, usually resulting in gene silencing via translational repression or target degradation.The human genome may encode over 1000 miRNAs which may target about 60% of mammalian genes. 

Other posts of interest on the blog in relation to epigenetics:

04 Jan 2013
Research: Epigenetics influence visual function. Deimination restores inner retinal visual function in murine demyelinating disease. Enriquez-Algeciras M, Ding D, Mastronardi FG, Marc RE, Porciatti V, Bhattacharya SK.
15 Aug 2010
Furthermore, a relatively new field of genetics, called epigenetics, which refers to modifications of DNA that regulate the function of the genome, has also been shown to differ between MZ twins. MZ twins discordant for a ...
22 Jun 2011
This could be due to epigenetics, i.e. the imprinting on the genome that is known to occur (see previous post), or the possible vertical transmission of a virus from mother to child. Vertical transmission is well described with ...
29 Apr 2011
There is now convincing evidence for an epigenetic component to MS, with maternal parent-of-origin, transgenerational (grandparental) and early life (month of birth) effects, as well as the increasing sex ratio of the disease.

1 comment:

  1. Hope you don't mind me sharing my passion for free online courses (MOOCs) here, but there's an interesting-looking course coming up this summer in epigenetics in Coursera. I took a genetics course this way last summer, and it was fantastic. Maybe Prof. G will think about teaching one of these courses someday ....

    https://www.coursera.org/course/epigenetics

    ReplyDelete

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