A Comeback for Lamarckian Evolution?

The effects of an animal's environment during adolescence can be passed down to future offspring, according to two new studies. If applicable to humans, the research, done on rodents, suggests that the impact of both childhood education and early abuse could span generations. The findings provide support for a 200-year-old theory of evolution that has been largely dismissed: Lamarckian evolution, which states that acquired characteristics can be passed on to offspring.

"The results are extremely surprising and unexpected," says Li-Huei Tsai, a neuroscientist at MIT who was not involved in the research. Indeed, one of the studies found that a boost in the brain's ability to rewire itself and a corresponding improvement in memory could be passed on. "This study is probably the first study to show there are transgenerational effects not only on behavior but on brain plasticity."

In recent years, scientists have discovered that epigenetic changes--heritable changes that do not alter the sequence of DNA itself--play a major role in development, allowing genetically identical cells to develop different characteristics; epigenetic changes also play a role in cancer and other diseases. (The definition of epigenetics is somewhat variable, with some scientists limiting the term to refer to specific molecular mechanisms that alter gene expression.) Most epigenetic studies have been limited to a cellular context or have looked at the epigenetic effects of drugs or diet in utero. These two new studies are unique in that the environmental change that triggers the effect--enrichment or early abuse--occurs before pregnancy. "Give mothers chemicals, and it can affect offspring and the next generation," says Larry Feig, a neuroscientist at Tufts University School of Medicine, in Boston, who oversaw part of the research. "In this case, [the environmental change] happened way before the mice were even fertile."

In Feig's study, mice genetically engineered to have memory problems were raised in an enriched environment--given toys, exercise, and social interaction--for two weeks during adolescence. The animals' memory improved--an unsurprising finding, given that enrichment has been previously shown to boost brain function. The mice were then returned to normal conditions, where they grew up and had offspring. This next generation of mice also had better memory, despite having the genetic defect and never having been exposed to the enriched environment.

The researchers also looked at a molecular correlate of memory called long-term potentiation, or LTP, a mechanism that strengthens connections between neurons. Environmental enrichment fixed faulty LTP in mice with the genetic defect; the fixed LTP was then passed on to their offspring. The findings held true even when pups were raised by memory-deficient mice that had never had the benefits of toys and social interaction. "When you look at offspring, they still have the defect in the protein, but they also have normal LTP," says Feig. The findings were published today in the Journal of Neuroscience.

"If the findings can be conveyed to human, it means that girls' education is important not just to their generation but to the next one," says Moshe Szyf of McGill University, in Montreal, who was not involved in the research.

In a second study, researchers found that rats raised by stressed mothers that neglected and physically abused their offspring showed specific epigenetic modifications to their DNA. The abused mice grew up to be poor mothers, and appeared to pass down these changes to their offspring.

The Journal of Neuroscience, February 4, 2009, 29(5):1496-1502; doi:10.1523/JNEUROSCI.5057-08.2009 Abstract;

The idea that qualities acquired from experience can be transmitted to future offspring has long been considered incompatible with current understanding of genetics. However, the recent documentation of non-Mendelian transgenerational inheritance makes such a "Lamarckian"-like phenomenon more plausible. Here, we demonstrate that exposure of 15-d-old mice to 2 weeks of an enriched environment (EE), that includes exposure to novel objects, elevated social interactions and voluntary exercise, enhances long-term potentiation (LTP) not only in these enriched mice but also in their future offspring through early adolescence, even if the offspring never experience EE. In both generations, LTP induction is augmented by a newly appearing cAMP/p38 MAP kinase-dependent signaling cascade. Strikingly, defective LTP and contextual fear conditioning memory normally associated with ras-grf masked in the offspring of enriched mutant parents. The transgenerational transmission of this effect occurs from the enriched mother to her offspring during embryogenesis. If a similar phenomenon occurs in humans, the effectiveness of one's memory during adolescence, particularly in those with defective cell signaling mechanisms that control memory, can be influenced by environmental stimulation experienced by one's mother during her youth.

Source: MIT Technology Review
Source: The Journal of Neuroscience