With Father’s Day just around the corner, it’s the time of year we think about how we can “enrich” Dad’s life with power tools, gift cards, and hand-made crafts. But maybe we should be looking into enriching Dad’s cognitive environment because it turns out that he can pass those benefits on. In mice, the environmental enrichment (EE) paradigm is achieved by a combination of physical exercise and cognitive training. It has been shown to improve hippocampal synaptic plasticity, changes in synaptic strength that contribute to learning and memory. These effects have also been observed in the offspring of EE mice raised normally. The mechanism of these effects remains unknown; however, the determinantal cognitive effects of paternal early-life and chronic stress as well as the effects of paternal diet are transmitted intergenerationally via sperm miRNAs. Whether this same miRNA phenomena is responsible for passing positive effects has remained unknown.
To identify the specific miRNAs involved in sperm transmission of environmental exposures, the lab of André Fischer at The German Center for Neurodegenerative Diseases sought to examine the mechanisms behind the known EE effects in adult mice. They exposed 10-week-old mice to EE training for 10 weeks, then mated them to home-cage (HC) controls raised in a standard, non-enriched environment. The EE protocol consisted of large cages running wheels, tunnels, and toys that were changed frequently. They then used qPCR to assess specific miRNA candidates. Here’s what they found:
- Consistent with previous work, EE male mice and their offspring have increased hippocampal synaptic plasticity and cognitive measures
- Male and female F1 offspring of EE males with HC control females have increased hippocampal LTP at 12 weeks of age compared to HC x HC offspring
- The LTP effect is not present in the F2 generation and therefore not transmitted by transgenerational epigenetic inheritance
- Six miR212/132 cluster miRNAs were selected for analysis via qPCR based on a literature search for miRNAs expressed in sperm & brain, with a role in memory & brain development
- miR132 and miR212 are upregulated both in hippocampus of EE mice after just two weeks, and in sperm after 10 weeks of EE
- Offspring born to oocytes injected with RNA from EE mouse sperm exhibit enhanced LTP and improved cognitive score
- The effects are reversed to HC levels if miR212/132 LNA antisense inhibitors are co-administered
The mechanisms by which sperm miRNA levels are affected by EE and how these changes affect offspring brain development are unknown. The fact that hippocampal miR132 and miR212 were upregulated after just 2 weeks, may indicate a transmission of this change from the brain to the sperm, perhaps via circulating exosomes. Much more research is needed to understand this complex phenomenon. So, while you already inherited your sperm RNAs, this Father’s Day lets think about how we can enrich things for all Dads. We just may be enhancing the synaptic plasticity of two generations.
Enrich yourself with all the details over at Cell Reports, April 2018