Age-related memory loss -- RbAp48

All adults suffer from some form of memory loss as they age. Researchers seeking to understand the biological causation for age-related memory loss conducted the following experiments that focused on the hippocampus, the region in the brain that plays an important role in memory and information consolidation.

Experiment 1

Scientists analyzed two different regions of the hippocampus known as the dentate gyrus (DG) and the entorhinal cortex (EC) to see if the expression of proteins in those regions were the same in all adults regardless of age. One protein in particular stood out: RbAp48, a protein associated with histone acetylation and promoter regulation. The expression of RbAp48 in theses hippocampal regions versus age is shown in Figure 1.

Experiment 2

Researchers engineered mice that express an inactive form of RbAp48 known as dominant-negative mice (RbAp48-DN). These researchers compared the same youthful aged wild-type mice to youthful aged RbAp48-DN mice. The mice were tested for hippocampal-dependent dysfunction with an object recognition test. In this test, the mice were exposed to two objects and were given time to learn and explore them. In 24 hours the mice were returned to the objects but this time one of the original objects was replaced with a new novel object. In 48 hours the mice were returned again and exposed to the same original object that was there in the 24-hour test, but the second object was yet another novel object. The same object recognition test was also performed on young and old wild-type mice. The results of these tests are measured by a discrimination index defined by the following equation, where object A is the novel object in the 24- and 48-hour tests.

The results of the test are in Figure 2.