A study reveals that the severity of learning disorders may depend not only on the child's environment but also on the mother's environment when she was young.

The researchers studied the brain function of pre-adolescent mice with a genetically-created defect in memory. When these young mice were enriched by exposure to a stimulating environment – including novel objects, opportunities for social interaction and voluntary exercise – for two weeks, the memory defect was reversed. The work showed that this enhancement was remarkably long-lasting because it was passed on to the offspring even though the offspring had the same genetic mutation and were never exposed to an enriched environment. 

Previous research has shown that environmental exposures during pregnancy can affect offspring. "A striking feature of this study is that enrichment took place during pre-adolescence, months before the mice were even fertile, yet the effect reached into the next generation," said Larry Feig, PhD, professor of biochemistry at Tufts University School of Medicine and member of the biochemistry and neuroscience programs at the Sackler School of Graduate Biomedical Sciences at Tufts University. 

"The offsprings' improved memory was not the result of better nurturing by mothers who were enriched when they were young. When the offspring were raised by non-enriched foster mothers, the offspring maintained the beneficial effect," said co-author Junko Arai, PhD, postdoctoral associate in Feig's laboratory. 

"The effect lasted until adolescence, when it waned, suggesting that this process is designed specifically to aid the young brain," continued Shaomin Li, PhD, MD, co-author, former postdoctoral associate in Feig's laboratory, now at Brigham and Women's Hospital. 

"This example of 'inheritance of acquired characters,' was first proposed by Lamarck in the early 1800s. However, it is incompatible with classical Mendelian genetics, which states that we inherit qualities from our parents through specific DNA sequences they inherited from their parents. We now refer to this type of inheritance as epigenetics, which involves environmentally-induced changes in the structure of DNA and the chromosomes in which DNA resides that are passed on to offspring," said Feig. 

Previous research by Feig and his team showed that a relatively brief exposure to an enriched environment in both normal and memory-deficient mice unlocks an otherwise latent biochemical control mechanism that enhances a cellular process in nerve cells called long-term potentiation (LTP), which is known to be involved in learning and memory. This enhancement was detected in pre-adolescent mice but not in adult mice, reflecting the brain's higher plasticity in the young. 

Feig concluded that the transgenerational inheritance of the effect of an enriched environment may be a mechanism that has evolved to protect one's offspring from deleterious effects of sensory deprivation, which may be particularly potent in the young and exacerbated in the learning disabled.

Junko Arai and Shaomin Li, first authors, contributed equally to the paper. Dean M. Hartley, PhD, of Rush University Medical Center is also an author. 

The work was supported by the National Cancer Institute of the National Institutes of Health because these findings were derived as an offshoot of the Feig lab's long-term experience working on Ras proteins that are involved in cancer. Fundamental principles of how Ras proteins function gained by studying its role in cancer expedited subsequent studies on Ras function in the brain. This work highlights how major breakthroughs can arise by allowing researches to follow new leads that cross disciplines. The work was also supported by the Tufts Center for Neuroscience Research. 

Article: Arai J, Li S, Hartley DM, and Feig LA. The Journal of Neuroscience. 2009. (February 4); 29(5): 1496-1502. "Transgenerational Rescue of a Genetic Defect in Long-Term Potentiation and Memory Formation by Juvenile Enrichment." Published online February 3, 2009, doi: 10.1523/JNEUROSCI.5057-08.2009