Author: Ayotenu Dosumu
Artist: Luli Fukukawa
Editor: Atufa Shabnum
There’s long been debate on whether a person owes their identity to their genetic makeup or their life experiences–the classic “Nature versus Nurture” argument. However, the emerging field of neuroepigenetics adds more nuance and complexity to this debate, suggesting that traumas experienced by our ancestors may be inherited by us and explain our own behaviour.
Basic Principles
Neuroepigenetics is the intersection between neuroscience and epigenetics. The discipline studies heritable changes in gene expression without modification to the genetic code, examining how this affects the cells of the central nervous system (CNS) and the subsequent implications for behaviour and brain function. The mechanisms for changes in gene expression involve DNA methylation and changes in chromatin structure via histone modification. When methyl groups are added to CpG islands of promoter regions, it prevents the binding of transcriptional factors to DNA leading to suppressed gene expression. Histone modifications can lead to chromatin being packaged densely so the gene is physically inaccessible to transcription factors, once again leading to suppression or for chromatin to be loose and easily accessible leading to upregulation of a gene. It’s thought a traumatic event can trigger these mechanisms, affecting specific combinations of an organism’s genes, resulting in a behavioural change.
Past – Present Interaction
Traumatic events aren’t only confined to war experiences but can be physical, sexual, and verbal violence, abuse, neglect, and humiliation – experiences that can affect any person. Trauma’s effects vary depending on the age it was experienced and the duration. Researchers, including Isabelle Mansuy, studied these effects in mice exposed to chronic and unpredictable maternal separation from postnatal day 1 to 14. They found the mice exhibited depressive-like behaviours and changes in response to aversion environments in adulthood. The offspring of males subjected to maternal separation also expressed these behavioural changes. Furthermore, there was a change in the profile of DNA methylation in promoter regions of genes in the sperm cells of separated males with changes in DNA methylation in the brains of the offspring.
So, what does this mean? The ‘trauma’ experienced by the mice in early childhood, caused a behavioural change potentially linked to epigenetic changes in gene expression. These changes were passed onto the offspring of separated male mice, leading to similar behaviour being exhibited by their offspring despite not experiencing maternal separation themselves.
This highlights another important aspect of transgenerational epigenetic transmission; Epigenetic changes affecting the reproductive cells may be responsible for the manifestation of symptoms in offspring.
The Future
Large-scale genome-wide associated studies have identified over 100 loci associated with different neuropsychiatric and neurodegenerative disorders. Epigenetic changes stemming from traumatic events are believed to affect these regions and therefore play a role in these disorders. Considering this, various epigenome targeting drugs are in clinical trials with hopes of reversing environmentally induced epigenetic changes to the CNS. However, epidrugs aren’t yet ready for widespread clinical use due to the susceptibility of the CNS to their “genotoxicity, low stability, multi-targeted and multi-cellular effects.” Moreover, with the still limited understanding of neuroepigenetics and its implications, a linking of observations from multiple brain regions and large populations of people to cell-type-specific analysis is required. Ultimately, neuroepigenetic research may not only be the key to understanding who we are and our behaviour, but also provide hope for more effective treatment of neuropsychiatric and neurodegenerative disorders.
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