Abstract
According to World Health Organization (WHO), in 2020, around 300 million children suffered from physical and/or psychological violence and 264 million people suffer from depression. Albeit constant advances made towards the development of new therapies, stress related disorders are still leading causes of burden of disease worldwide affecting over 350 million of people (WHO), highlighting the need for novel and innovative therapeutics and a deeper understanding of the mechanisms underlying these events.
My PhD project (MetCOEPs) aimed to study and understand the mechanisms linking early life stress (ELS), in the form of maternal separation, and the consequences it brings in adulthood. This early period is already known to have a great impact in the development of diseases such as depression, anxiety, diabetes and cardiovascular diseases. Particularly, maternal separation is widely associated with neurodevelopment impairment, with brain regions such as the cortex, amygdala and hippocampus being highly susceptible. Although some studies also associate ELS and poor immune system functionality, little is known about the mechanisms underlying such events. The first part of my PhD aimed at assessing the immune phenotype of animals that were maternal separated in the first days of life. Particularly, I studied how the immune system would behave when facing exposure to external stressors, and if the response would be similar in rodents and humans.
In a second phase, I also studied the impact on ELA on the brain development. Through magnetic resonance imaging, I was able to determine the different impacted regions and follow those changes through RNA analysis. Genes involved in such changes were identified and associated with pathways that can be manipulated in the future, in order to prevent further damages.
Finally, in the last year of my PhD I investigated the role of DNA methylation in neurodevelopment. 5-methylcytosine was already described to have a great impact on this important period of life but not so much was known about 6-methyladenine. In a collaboration project, I was able to identify this modification and set a base-calling software to be able to read targeted sequencing results from specific brain regions.
My PhD project (MetCOEPs) aimed to study and understand the mechanisms linking early life stress (ELS), in the form of maternal separation, and the consequences it brings in adulthood. This early period is already known to have a great impact in the development of diseases such as depression, anxiety, diabetes and cardiovascular diseases. Particularly, maternal separation is widely associated with neurodevelopment impairment, with brain regions such as the cortex, amygdala and hippocampus being highly susceptible. Although some studies also associate ELS and poor immune system functionality, little is known about the mechanisms underlying such events. The first part of my PhD aimed at assessing the immune phenotype of animals that were maternal separated in the first days of life. Particularly, I studied how the immune system would behave when facing exposure to external stressors, and if the response would be similar in rodents and humans.
In a second phase, I also studied the impact on ELA on the brain development. Through magnetic resonance imaging, I was able to determine the different impacted regions and follow those changes through RNA analysis. Genes involved in such changes were identified and associated with pathways that can be manipulated in the future, in order to prevent further damages.
Finally, in the last year of my PhD I investigated the role of DNA methylation in neurodevelopment. 5-methylcytosine was already described to have a great impact on this important period of life but not so much was known about 6-methyladenine. In a collaboration project, I was able to identify this modification and set a base-calling software to be able to read targeted sequencing results from specific brain regions.
| Original language | English |
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| Publication status | Published - 4 Jun 2021 |