Paternal Exercise Epigenetically Enhances Expression and Inheritance of a Key Gene Involved in Learning and Memory

Man Running on Beach Epigenetics

It is widely known that a mother has substantial influence over her offspring during prenatal development. Her eating, exercising, and overall lifestyle can have lifelong effects for her children. But what about the father? It turns out that fathers are not off the hook when it comes to prenatal development, and his physical activity may have lasting effects on the epigenetic regulation of gene expression in an area of the brain important for learning and memory: the hippocampus. First, a summary of exercise and its effects on one gene important for learning and memory.

Have you ever crammed for an exam, knowing that you probably could have studied harder and longer to be better prepared? We can liken that experience to what’s called a “sub-threshold learning event”, which is an exposure to something new that does not lead to a long-term memory for it. A study published by researchers at the University of California, Irvine and the University of Vermont showed that exercising before exposure to a sub-threshold learning event can transform that event into a long-term memory by altering the expression of a gene found in the hippocampus called brain-derived neurotrophic factor (bdnf). This occurs through two important epigenetic mechanisms: DNA methylation and histone acetylation.

Think about DNA methylation and histone acetylation as having opposing effects: DNA methylation represses gene expression, while histone acetylation promotes gene expression. A class of enzymes called DNA methyltransferases (DNMTs) catalyzes methylation of DNA bases. This typically occurs on the base cytosine in cytosine-phosphate-guanosine (CpG) “islands” present in the human genome. This methylated DNA can repress gene expression by interfering with the binding of proteins called transcription factors at regulatory sites of DNA which would normally promote gene expression. Methylated DNA can also recruit other proteins to alter the DNA structure such that it is no longer accessible to transcriptional activators.

Histone acetylation, on the other hand, does the opposite. When a class of enzymes called histone acetyltransferases (HATs) bind to histones (special proteins with DNA wrapped around them), they change the DNA structure such that transcriptional activators are able to bind to and promote gene expression. Exercise, coupled with an increase in histone acetylation, increases bdnf expression and primes the brain for learning and memory. Check out this article for more information on paternal epigenetic inheritance of DNA methylation and histone acetylation.

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Since bdnf is such an important gene for learning and memory, its expression is tightly regulated. A review paper published by researchers at the University of California, Los Angeles and the Universidade Federal de São Paulo outlined studies showing the effects of exercise on methylation and acetylation of bdnf in the hippocampus. Several studies they cite point to a regulatory role of these epigenetic mechanisms in synaptic plasticity (the ability of your brain network to rewire itself) and learning and memory. The general trend is an increase in histone acetylation and a decrease in DNA methylation. Both lead to enhanced gene expression, in this case of bdnf, which may help explain why exercise enhances memory.

SEE ALSO:   The Epigenetics of Sleep: 3 Reasons to Catch More Zzz’s

So the next time you want to learn something quickly and remember it for longer, exercise a bit before looking it over! And if you want to do your future children a favor, it turns out that the effects of exercise on memory can also be passed down from generation to generation!

A closer look at the father’s physical condition and epigenetic inheritance

Through a process called “epigenetic inheritance”, epigenetic “tags” like methylation and acetylation can be passed from generation to generation. For example, taste preferences can be epigenetically inherited. A mother’s prenatal stress negatively affects the development of her offspring. What about the effects of exercise? Or the father’s lifestyle? It turns out that physical activity can epigenetically reprogram sperm, which can influence the development of offspring through epigenetic inheritance. This is true in both mice and humans. A study published in Cell Metabolism demonstrated that the methylation profile of sperm differs between obese men and lean men. Weight loss induces changes in DNA methylation specifically at genomic locations associated with appetite. In addition, three months of aerobic exercise on a treadmill is enough to alter DNA methylation in sperm. It turns out that one of the genes whose DNA methylation profile is altered is bdnf! Since exercise can significantly alter the epigenetic landscape of sperm, can that be passed down? A study published by researchers at the Tianjin Medical University showed that paternal aerobic exercise before mating increases bdnf expression in the hippocampus in male offspring. This also corresponded with an increase in learning and memory in the male offspring.

It turns out that a father’s sperm contribution contains blueprints for much more than his genes – his epigenetics, which are shaped by his life experiences, also influence the development of his offspring!         

References:

  1. Intlekofer et al., 2013. Exercise and Sodium Butyrate Transform a Subthreshold Learning Event into Long-Term Memory via a Brain-Derived Neurotrophic factor-Dependent Mechanism. Neuropsychopharmacology 38(10):2027-34.
  2. Fernandes et al., 2017. Physical exercise as an epigenetic modulator of brain plasticity and cognition. Neurosci Biobehav Rev 80:443-456.
  3. Donkin et al., 2016. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans. Cell Metab 23(2):369-78.
  4. Denham et al., 2015. Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics 7(5):717-31.
  5. Yin et al., 2013. Paternal treadmill exercise enhances spatial learning and memory related to hippocampus among male offspring. Behav Brain Res 15;253:297-304.

Disclaimer: The points made herein represent a speculative opinion of the author based on some related scholarly publications on animal studies and may not actually apply to humans.

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Matthew Mahavongtrakul
About Matthew Mahavongtrakul 1 Article
Matthew Mahavongtrakul graduated with a PhD in Biological Sciences from the University of California, Irvine. When he first learned of epigenetics as an undergraduate, he became fascinated by the topic and integrated it into his dissertation work focused on molecular mechanisms of Alzheimer's Disease. He currently teaches epigenetics in an undergraduate Molecular Biology course and is excited to continue contributing to the field.

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