Commonly, the drug Aricept (donepezil) is prescribed for patients with Alzheimer’s disease to help relieve some of the symptoms of dementia. Although it does not help everyone (and may even hurt some), many patients find their memories improve significantly while taking this medicine. Anecdotally, some patients have even reported a new ability to reclaim distant scenes from their childhood while on Aricept. But what if memory could be improved in a permanent way? Such a feat may be on the horizon: A team of scientists found that stimulation of a specific gene (in adult mice) prompted growth of new neurons in the hippocampus, and this led to faster learning and better memories.

"Memory loss is a major health problem, both in diseases like Alzheimer's, but also just associated with aging," said Dr. Yanhong Shi, lead author of the study and a neurosciences professor at City of Hope. Shi believes the effects of this gene — a nuclear receptor called TLX — offers insight for developing treatments that might improve cognitive performance in elderly patients or those who have suffered a neurological disease or brain injury.

What is the hippocampus?

The bulk of brain development happens before a person is even born. That said, it has long been known that there are periods in childhood and young adulthood when the brain experiences bursts of new growth. More recently, scientists have found evidence of neurogenesis in later adulthood; unexpectedly, these new brains cells grow mostly in the hippocampus, the region of the brain where information becomes consolidated. The hippocampus is located in the medial temporal lobe and is crucial for helping us form declarative memories, those that can be consciously recalled, such as birth dates and historical facts. Dr. Gyorgi Buzsaki likens this region to a search engine, allowing a fast and efficient search of memories, an activity which is essential for planning as well as generating new ideas.

For the new study, Shi and her colleagues investigated the TLX gene and what would happen if they found a way to over-express it. Shi and her colleagues had previously looked at what happens when TLX is under-expressed. The brains of TLX-null mice showed no obvious defects during the embryo stage, but when the mice matured, they suffered from inflammation of the eye, aggressiveness, severe defects in the limbic system of their brains, reduced copulation, and progressively violent behavior. "In our [new] study, we manipulated the expression of this receptor by introducing an additional copy of the gene — which obviously we cannot do outside the laboratory setting,” said Shi in a press release.

What did Shi and her research team discover? Over-expression of the gene was associated with a physically larger brain, as well as the ability to learn a task quickly. Furthermore, over-expression of the gene was linked with the ability to remember, over a longer period of time, whatever had been learned.

Understanding the link between this gene and neurogenesis, Shi believes, is an important step in developing therapies to address impaired learning and memory that goes hand in hand with neurodegenerative diseases and aging. “The next step is to find the drug that can target this same gene," Shi said.  

 

Source:  Murai K, Qu Q, Sun G, et al. Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model. Proceedings of the National Academy of Sciences. 2014.