Is the cause of senile dementia epigenetic changes?

Researchers at the European Institute of Neurobiology (Göttingen, Germany), working under the leadership of Andre Fischer, have identified significant differences in the epigenetic profiles of a specific region of one of the histones (proteins that provide dense DNA packaging) in young and old mice. This causes differences in the level of expression of a number of genes in these two groups of animals. Moreover, it turned out that such epigenetic changes are the cause of impaired ability of old mice to learn.

The researchers believe that they have managed to identify an important epigenetic mechanism, the disruption of which can be used as a biomarker of senile dementia. The results of their work were published in the journal Science on May 7 in the article "Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice".Earlier studies have shown that changes in the expression of certain genes can trigger the aging process.

Considering that histone acetylation changes the shape of chromatin and, accordingly, changes gene expression (and also, as the results of a recent study showed, participates in the formation of long-term memory), the authors decided to study the possible role of changes in the nature of histone acetylation in the deterioration of cognitive function.

They exposed the young (3 months) and the old (16 months) mice were given a set of training tests, after which gene expression was analyzed in the cells of the hippocampus of animals – a region of the brain that was one of the first to suffer from dementia.

Upon completion of the learning process, an increase in the level of acetylation of the 12th lysine residue of histone H4 (H4K12) was observed in the hippocampal cells of young mice, which was not observed in the hippocampus of old animals. As a result, the expression of a number of genes changed in young mice, most of which are associated with the process of memorization. Accordingly, no such changes were observed in old mice.

To test the hypothesis that specific changes in the histone acetylation profile may be the cause of impaired learning ability, researchers injected old animals with a drug that inhibits the enzyme histone deacetylase and, accordingly, stimulates histone acetylation. As a result, after performing the tests, the level of H4K12 acetylation increased in animals, which, apparently, made it easier to memorize and complete tasks.

According to Fischer, his group intends to study the mechanisms underlying cognitive impairment in Alzheimer's disease. They suggest that stimulating histone acetylation with histone deacetylase inhibitors may prove to be an effective approach to the treatment of senile dementia.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Epigenetic change ups dementia?

12.05.2010