Methylation, active in adult brains

Mar 15, 2007 08:50 GMT  ·  By

Memory is important: from not mixing your lovers' name to the learning processes...

Neurons must intervene in the activity of the genes to form long lasting memories, usually by employing proteins that inhibit or exhibit the expression of specific DNA patches correlated to specific genes.

But now a research team discovered a new neuronal way of controlling gene activity: by chemically modifying the genes themselves (the DNA portions). While growing, the brain employs "epigenetic" paths to make long-term changes in gene expression. For instance, enzymes that determine histones (proteins that keep DNA tightly packaged) structure give or impede the access to certain genes.

Another method is DNA methylation, when a methyl group added to a DNA patch silences a gene.

But until now, epigenetic was regarded as a phenomenon occurring only during the brain development, but not in the fully developed mature nervous system.

Neurobiologists Courtney Miller and David Sweatt of the University of Alabama, Birmingham experimented on rats, injecting them with a drug that stopped DNA methylation soon after the rats had received three mild electrical shocks. Rats remember such an unpleasant experience and next time, after 24 hours, when put back in the same enclosure, they experienced panic.

But not in the case of the injected rats. They displayed about one-fourth of the panic behavior of uninjected rats, thus they experienced a much weaker memory. The team focused for specific memory-related genes which were impaired by DNA methylation after the shock-box experiment and discovered that weak memory was linked to increased methylation of a gene called PP1, previously linked to learning and memory.

At the same time, they observed decreased methylation and increased expression of a memory-promoting gene called reelin. "The methylation changes in both genes favor learning and memory. Along with recent studies on histone modifications in the adult nervous system, the new work adds to growing evidence that epigenetic mechanisms may contribute to learning and memory," said Sweatt.

"Classically, DNA methylation has been viewed as one of the most permanent ways to modify DNA and alter gene expression. But in the new study, methylation levels of PP1 and reelin changed within an hour of learning and returned to normal 24 hours later. That suggests that DNA methylation can be a far more dynamic process than many researchers assumed," said Lisa Monteggia, a neurobiologist at the University of Texas Southwestern Medical Center in Dallas.