Where did I leave my car keys? Do I come in this room to get something? And what was the name of that person?
Aging often means getting a little forgetful. Now researchers working with mice believe they have found a new reason. They identified the molecular changes in the brain of mice that prevent aging learning genes and switching memory as they are in younger animals. If the results translate into humans, they could one day lead to drugs that stave off dementia or even the normal cognitive decline in old age. Indeed, a certain class of drugs already in development to treat cancer could fit the bill.
changesPrevious studies have found age-related gene expression in the hippocampus, an important memory center in the brain. Other work involved tiny histone spools of proteins that control gene expression by winding or unwinding DNA in learning and memory. Neuroscientist Andrew Fischer of the European Neuroscience Institute in Göttingen, Germany, and his colleagues wanted to probe the connection histone further. They hypothesized that aging can change the operation of the histones, which causes alterations in the expression of genes that contribute to memory impairment.
To test the idea, Fischer and colleagues compared young and old mice. old mice do not have the car keys to lose track, but they are struggling to remember a place where they once received an unpleasant surprise or hidden platform in a water basin disorder. The team found staggering differences in gene expression between young 3 month old mice and 16-month-old mice (equivalent to the average age at the end of man). An hour after being trained to associate a particular room with an imminent shock to the foot, nearly 2,000 genes in the hippocampus became more active in younger mice compared with only six genes in aged mice.
The reason seems to be that in younger mice association between the bedroom and the results of shock in a type of chemical modification, called acetylation, to a specific site on the protein histone H4K12. Histone acetylation causes to decelerate their DNA, thus allowing gene expression to proceed, if acetylation decrease generally reduced gene expression.
Indeed, when the researchers injected a drug into the hippocampus of aged restore acetylation mice, the gene expression profiles of these mice had look similar to those of their younger counterparts. Furthermore, this treatment has improved the old mice's ability to remember a foot shock, as evidenced by a fearful behavior "freeze" when they reviewed the room a day later, the team reports in number tomorrow Science .
"These studies bring us one step closer to understanding memory loss related to age and closer to developing a drug that might help boost memory in aging associated with memory loss' says David Sweatt, a neuroscientist at the University of Alabama, Birmingham. Sweatt notes that recent studies by his group and Ottavio Arancio and colleagues at Columbia University found that drugs that stimulate histone acetylation can improve memory in mouse models of Alzheimer's disease. Some of these drugs, called histone deacetylase inhibitors are already approved for the treatment of cancer, and more are in the pipeline, said Arancio. But he warns that it remains to be seen if they are precise enough to work as memory enhancers without causing serious side effects. Fischer suggests that drugs that specifically enhance H4K12 acetylation, if they can be developed, could do the trick.
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