Summary: New research in mice shows that both physical exercise and mental stimulation can influence the learning ability of their offspring through RNA-based, epigenetic mechanisms.
Source: DZNE
Physical activity and cognitive training not only benefit the individual brain, they can also produce measurable advantages in the next generation — at least in mice. These intergenerational effects are carried by specific RNA molecules that accumulate in the brain and in sperm after periods of exercise and mental stimulation.
Researchers led by Prof. André Fischer at the German Center for Neurodegenerative Diseases (DZNE) in Göttingen and Munich and the University Medical Center Göttingen (UMG) describe these findings in Cell Reports.
For decades, the prevailing view in genetics held that acquired skills or experiences could not change DNA sequence and therefore could not be inherited. However, accumulating evidence has shown that environmental factors such as diet, stress, and trauma can produce epigenetic changes that influence health across generations. Epigenetic inheritance refers to mechanisms that alter gene activity without changing the DNA code itself, and these mechanisms can sometimes be transmitted to offspring.
Inherited learning skills
Fischer and colleagues examined whether the cognitive benefits of physical and mental activity could be passed to offspring. It is well established that exercise combined with cognitive challenges strengthens synaptic plasticity and improves learning and memory, and it can reduce the risk of neurodegenerative disease. In a controlled mouse study, the team exposed adult male mice to an enriched environment that encouraged movement, exploration, and mental engagement. The offspring of these males performed better in behavioral tests that assess learning and memory than offspring of control males kept in standard conditions.
At the neural level, offspring of enriched males showed enhanced synaptic plasticity in the hippocampus, the brain region most closely associated with learning and memory. Synaptic plasticity reflects how effectively neurons change their connections and signaling in response to experience, and it is considered a cellular basis for learning.
Evidence for RNA-mediated transmission
To identify the molecular basis of this intergenerational effect, the researchers focused on paternal contributions via sperm. Sperm carry not only paternal DNA but also a diverse set of RNA molecules. The team isolated RNA from the sperm of males that had experienced environmental enrichment and injected these sperm RNA extracts into fertilized mouse eggs. Offspring that developed from those eggs also displayed improved hippocampal synaptic plasticity and superior performance on learning tasks, indicating that sperm RNA can transmit cognitive benefits from fathers to offspring.
Tracking down the responsible RNA
Further experiments narrowed the effect to specific small non-coding RNAs. Two microRNAs — miR-212 and miR-132 — were identified as key contributors to the inherited improvement in cognitive function. MicroRNAs are short RNA molecules that regulate gene expression by fine-tuning which genes are translated into proteins. The researchers found increased levels of miR-212 and miR-132 in both the brains and the sperm of mice after exposure to the enriched environment.
Previous work has linked miR-212 and miR-132 to synapse formation and neuronal connectivity, which provides a plausible mechanism: elevated levels of these microRNAs in sperm may subtly alter early brain development in offspring, promoting improved neuronal connections and giving the next generation a modest cognitive advantage. As Prof. Fischer notes, this study is one of the first to connect a defined epigenetic phenomenon directly to specific microRNAs.
Although direct studies of epigenetic inheritance in humans are challenging, these mouse data suggest testable hypotheses for human research. The researchers plan to investigate whether similar increases of miR-212 and miR-132 occur in human sperm following periods of structured physical and cognitive activity.
Source: Marcus Neitzert, DZNE (reporting on the work of André Fischer and colleagues)
Original research article: “RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after Environmental Enrichment” by Eva Benito, Cemil Kerimoglu, Binu Ramachandran, Tonatiuh Pena-Centeno, Gaurav Jain, Roman Manuel Stilling, Md Rezaul Islam, Vincenzo Capece, Qihui Zhou, Dieter Edbauer, Camin Dean, and André Fischer. Published in Cell Reports, April 10, 2018. DOI: 10.1016/j.celrep.2018.03.059
Abstract (concise)
Exposure of adult male mice to an enriched environment combining physical exercise and cognitive stimulation enhances synaptic plasticity and learning in those males and also produces measurable cognitive benefits in their offspring. The intergenerational effect is mediated by altered sperm RNA content, with microRNAs miR-212 and miR-132 playing a central role. These findings demonstrate RNA-dependent epigenetic inheritance of an acquired cognitive advantage and identify specific microRNAs as mechanistic candidates for this type of transmission.
- Male mice that experience physical and mental enrichment can confer cognitive benefits to their offspring.
- Sperm RNA mediates this intergenerational transmission.
- miR-212 and miR-132 are implicated as important molecular mediators linking paternal experience to offspring brain function.
These results highlight how lifestyle and environment can produce molecular changes with consequences beyond a single individual, adding to the growing evidence that epigenetic mechanisms — including small regulatory RNAs — can shape brain development and cognitive outcomes in subsequent generations.