Groundbreaking research project shows how brain health can traverse generations

Your father's exercise routine may have made you smarter according to EU-funded researchers studying how lifestyle choices affect brain function and memory. The findings could lead to new treatments for neurodegenerative conditions such as Alzheimer's disease.

The groundbreaking research in the DEPICODE project, supported by the European Research Council, is deepening our understanding of epigenetics: how external influences such as physical activity, mental stimulation, diet and stress influence how our cells read genetic information. While it is widely recognised that exercise is good for our brains –strengthening neural connections to sharpen thinking and enhance memory – the DEPICODE team’s findings suggest some of these benefits can even be passed on to our children.

This research has important implications not only for prospective parents but also for the identification of biological signatures, or biomarkers, of epigenetic changes that can forewarn of disease, and for the development of new treatments.

We have gained a better understanding of the epigenetic processes that control cognitive function. Our data will help to develop therapeutic strategies to treat cognitive diseases in two ways: first, by identifying novel drug targets, and secondly, by providing evidence that epigenetic markers could serve as suitable biomarkers to assess disease risk and initiate preventive therapies."

André Fischer, DEPICODE Principal Investigator, German Center for Neurodegenerative Diseases, Göttingen

The team’s work has already led to one ongoing phase 2a clinical trial in Germany to assess whether Vorinostat, a cancer drug that affects gene expression, could also be a safe and effective treatment for patients with mild Alzheimer’s disease.

‘The DEPICODE project is embedded within our overall research approach to find epigenetic therapies and biomarkers for neurodegenerative diseases such as Alzheimer’s, the most common form of dementia, which causes an enormous social and economic burden worldwide,’ Fischer says.

Brain-boosting microRNAs

In this context, circulating microRNAs are of particular importance. These tiny molecules circulate in the blood and are known to influence the inner workings of genes. A cluster of them, known as miRNAs 212/132, are linked to brain development and memory, and hence could serve as potential biomarkers of cognitive disease.

In laboratory studies with mice, levels of miRNAs 212/132 have been found to increase in the hippocampus region of the brain after exercise, potentially strengthening neural connections between brain cells involved in memory and learning. Energetic mice with higher miRNAs 212/132 levels tend to perform better on cognitive tests than their sedentary counterparts – and, it turns out, so too do their offspring.

The DEPICODE researchers found that these microRNAs are also present in sperm as well as blood, and can transmit epigenetic benefits to a father’s offspring even if the mothers are sedentary and even if the pups never get on a running wheel.

‘We analysed exercise as a protective mechanism in cognitive disease and could show for the first time that exercising parents transmit a cognitive benefit to the next generation. This is mediated via epigenetic processes, namely altered microRNA expression in sperm, which produce the beneficial transgenerational effect,’ Fischer says.

To date, the research has been conducted with mice, but it is possible that the same effects occur in humans – a theory that is set to be explored further by Fischer and his team.

While the discovery might encourage prospective fathers to visit the gym, the broader findings about the role of microRNAs and the new insights gained in DEPICODE into epigenetic processes could lead to novel therapies for a range of neurological conditions, potentially benefiting millions of people worldwide.

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