Epigenetic Modifications Help Unlock the Molecular Mystery of Memory

Epigenetic Modifications and Memory

Memory is perhaps one of the most fascinating processes, one that guides us through life and helps make us who we are. Many believe memory is linked to synaptic plasticity, the ability to strengthen existing neuronal connections and form new ones. Although the creation of memories is not fully understood, new research uncovers evidence that offers a glimpse into the molecular mechanisms underlying this complex process. The molecular mechanisms that store experiences and alter brain cell connections to improve plasticity are thought to be crucial for both memory and learning. Now, scientists provide evidence lending support to the hypothesis that chemical tags on DNA assist in encoding memories. Researchers from the German Center for Neurodegenerative Diseases (DZNE) in Göttingen teamed up with coworkers at the DZNE Munich branch and investigated the epigenetic modifications associated with memory using a mouse model.

Previous research suggested that when memories are formed, a change in particular gene activity occurs. The researchers confirmed this in their study, published in Nature Neuroscience, and also found that epigenetic chemical tags may contribute substantially to the process of long-term memory. In a recent blog on What is Epigenetics?, an HDAC inhibitor drug was shown to epigenetically sharpen memory as well as treat cancer. By increasing the plasticity of neurons, this HDAC inhibitor could enhance memory in rats.

In this study, the research team, headed by Dr. Stefan Bonn and Professor André Fischer, trained mice to recognize a certain test environment in order to stimulate their long-term memory. Then they used brain tissue samples to determine the changes in gene activity triggered as a result of this learning task, known as contextual learning. The research focused on epigenetic modifications known as DNA methylation and histone modifications.

Epigenetic modifications are chemical tags on DNA that have the power to adjust gene expression without changing the underlying genetic sequence. DNA methylation, or the addition of a methyl group to DNA, is one of the most popular mechanisms. Histone modifications, which occur to the histone proteins around which DNA is wound, can also impact gene expression. Previous research has implicated chromatin modification by histone deacetylases (HDACs), which typically reduces transcription, in the formation of memory. The current study, on the other hand, indicated that DNA methylation changes that occurred to plasticity genes accompany the formation and maintenance of memory.

Dr. Magali Hennion from Stefan Bonn’s research group explained, “Research on epigenetic changes that are related to memory processes is still at an early stage. We look at such features, not only for the purpose of a better understanding of how memory works. We also look for potential targets for drugs that may counteract memory decline. Ultimately, our research is about therapies against Alzheimer’s and similar brain diseases.”

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The researchers discovered that histone modifications did occur, but didn’t have much effect on the genes related to neuroplasticity. They reported that “histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression.” Bonn, along with his team, detected epigenetic modifications in non-neuronal cells in the brain in addition to the modifications they found in nerve cells. Specifically, “long-lasting changes were almost exclusive to neurons,” but “learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning.”

“The relevance of non-neuronal cells for memory, is an interesting topic that we will continue to pursue,” said André Fischer, a representative for DZNE in Göttingen who is also a professor at the University Medical Center Göttingen (UMG). “Furthermore, our observations suggest that neuroplasticity is to a large extent regulated by DNA methylation. Although this is not a new hypothesis, our study provides an unprecedented amount of supporting evidence for this. Thus, methylation may indeed be an important molecular constituent of long-term memory. In such a case, methylation could be a sort of code for memory content and a potential target for therapies against Alzheimer’s disease. This is an aspect that we specifically want to focus on, in further studies.”

 

Source: Halder, R. et al. (2015). DNA methylation changes in plasticity genes accompany the formation and maintenance of memory. Nature Neuroscience, advance online publication.

Reference: German Center for Neurodegenerative Diseases (DZNE). New insights into the molecular basis of memory. 17 Dec 2015. Web.

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Bailey Kirkpatrick
About Bailey Kirkpatrick 149 Articles
Bailey Kirkpatrick is a science writer with a background in epigenetics and psychology and a passion for conveying scientific concepts to the wider community. She enjoys speculating about the implications of epigenetics and how it might impact our perception of wellbeing and the development of novel preventative strategies. When she’s not combing through research articles, she also enjoys discovering new foods, taking nighttime strolls, and discussing current events over a barrel-aged sour beer or cold-brewed coffee.
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