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Variações epigenéticas transgeracionais
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Abstract(s)
Existe evidência que as experiências vividas e a ambiência podem alterar os perfis
psicológicos e comportamentais, de modo a que os seres vivos se adaptem às novas ambiências.
Um ponto importante que tem sido discutido é se estas alterações podem ser transmitidas ao
longo de várias gerações, através da transmissão epigenética. A epigenética é o conjunto de
modificações químicas no DNA, que não alteram a sua sequência, mas codificam informação
que, por sua vez, influencia a expressão génica. Nova evidência tem desvendado os mecanismos
responsáveis pelas marcas epigenéticas, tais como a metilação do DNA, as modificações das
histonas e os RNA não codificantes. Outra questão pertinente que tem sido levantada é como
conseguem estas marcas do DNA escapar à reprogramação epigenética que ocorre no feto e nas
células germinativas primordiais. A reprogramação epigenética é responsável por eliminar as
modificações epigenéticas nos mesmos, permitindo o desenvolvimento de células totipotentes
e pluripotentes. Vários estudos têm identificado falhas neste processo que permitem a passagem
da informação para a gerações futuras. Todos estes mecanismos mencionados anteriormente
podem alterar a regulação génica devido à plasticidade do DNA e dar origem a respostas
adaptativas e não-adaptativas que, por sua vez, irão ser transmitidas às próximas gerações
devido à acomodação genética.
O stress e as experiências traumáticas são responsáveis por modificações epigenéticas
no DNA, que podem aumentar a suscetibilidade para a síndroma do stress pós-traumático
(PTSD) e outras alterações no organismo. Nesta monografia são analisados vários estudos sobre
PTSD, que mostram a transmissão de alterações fisiológicas ou comportamentais, tais como o
aumento de suscetibilidade para a PTSD, durante várias gerações. Também é aqui mencionado
o potencial efeito das toxinas ambienciais, tais como o álcool, o tabaco e a morfina, na
transmissão de marcas epigenéticas. Por fim, este trabalho refere o conceito de environmental
enrichment, que consiste na estimulação do cérebro através do contexto social positivo e da
atividade física. Este environmental enrichment pode estimular marcas epigenéticas positivas
e, deste modo, reverter as modificações feitas pelo stress traumático, surgindo assim, como uma
possibilidade de tratamento para os indivíduos afetados.
It is known that experiences and the environment can change the physiological and behaviour traits, in order for living beings to adapt to new environments. The central point of discussion is whether these modifications can be passed across several generations, through epigenetic transmission. Epigenetics refers to chemical modifications in DNA, which do not alter the genetic code, but carry non-genetic information, which in turn will change the gene regulation. New evidence as uncovered the epigenetic mechanism responsible for marking DNA, such as DNA methylation, histone modifications and non-coding RNA. One other question that has been proposed is how these changes in the DNA sequence can escape the epigenetic reprogramming which occurs in the fetus and in the primordial germ cells. This epigenetic reset is responsible for eliminating all the epigenetic marks in the fetus and in the primordial germ cells, in order to clean the epigenetic landscape and generate both totipotent and pluripotent cells. Several researchers have identified gaps in this process, leading to the transmission of non-genetic information to future generations. Together, these mechanisms can alter the gene regulation due to the DNA plasticity, and lead to adaptive and maladaptive changes in humans, that will be transmitted to next generations thought genetic accommodation. Stress and traumatic experiences are accountable for epigenetic modifications, that can lead to a higher susceptibility to PTSD and other changes in the organism. In this monography reviews several studies about PTSD, which enhanced the transmission of behaviours and physiological changes, such as an increased susceptibility to PTSD, across generations. The potential effects of environmental toxins, such as alcohol, tobacco, and morphine, in epigenetic inheritance are also discussed here. Lastly, this work presents the concept of environmental enrichment, which consists on the stimulation of the brain, through social surrounding, and physical activity. Environmental enrichment can trigger ‘positive epigenetic marks’ and revert the modifications made by traumatic stress, thus emerging as a treatment possibility for the affect individuals.
It is known that experiences and the environment can change the physiological and behaviour traits, in order for living beings to adapt to new environments. The central point of discussion is whether these modifications can be passed across several generations, through epigenetic transmission. Epigenetics refers to chemical modifications in DNA, which do not alter the genetic code, but carry non-genetic information, which in turn will change the gene regulation. New evidence as uncovered the epigenetic mechanism responsible for marking DNA, such as DNA methylation, histone modifications and non-coding RNA. One other question that has been proposed is how these changes in the DNA sequence can escape the epigenetic reprogramming which occurs in the fetus and in the primordial germ cells. This epigenetic reset is responsible for eliminating all the epigenetic marks in the fetus and in the primordial germ cells, in order to clean the epigenetic landscape and generate both totipotent and pluripotent cells. Several researchers have identified gaps in this process, leading to the transmission of non-genetic information to future generations. Together, these mechanisms can alter the gene regulation due to the DNA plasticity, and lead to adaptive and maladaptive changes in humans, that will be transmitted to next generations thought genetic accommodation. Stress and traumatic experiences are accountable for epigenetic modifications, that can lead to a higher susceptibility to PTSD and other changes in the organism. In this monography reviews several studies about PTSD, which enhanced the transmission of behaviours and physiological changes, such as an increased susceptibility to PTSD, across generations. The potential effects of environmental toxins, such as alcohol, tobacco, and morphine, in epigenetic inheritance are also discussed here. Lastly, this work presents the concept of environmental enrichment, which consists on the stimulation of the brain, through social surrounding, and physical activity. Environmental enrichment can trigger ‘positive epigenetic marks’ and revert the modifications made by traumatic stress, thus emerging as a treatment possibility for the affect individuals.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Epigenetic Epigenetic mechanism DNA methylation Transgenerational epigenetic inheritance PTSD Mestrado integrado - 2021