Genetically modified geniuses
An increase in the expression of a gene, the product of which plays a key role in the communication of nerve cells, leads to an improvement in the memory and mental abilities of experimental animals. This was reported by an international scientific group from the Medical College of Georgia (USA) and East China Normal University (China).
Researchers have named a new genetically modified (transgenic) line of rats "Hobby-Ji" (Hobbie-J) in honor of a smart rat – the heroine of a popular Chinese comic book. Transgenic rats were able to remember new objects (for example, toys they were given to play with) three times longer than Long Evans rats, which are considered the most intelligent of all animals of this species. It was the rats of the Long Evans line that became the object of genetic modification in the experiment. Also, Hobby-Gees coped much better with difficult tasks, for example, with memorizing the path in the maze where they had to find a piece of chocolate.
The results of this work were published ten years after the same group of researchers reported in the journal Nature about the breeding of a line of Doogie mice that had increased expression of the NR2B gene in the hippocampus – the center of memory and learning in the mammalian brain suffering from neurodegenerative diseases like Alzheimer's disease. Transgenic Hobby-Ji rats turned out to be very similar in their characteristics to the Doogie mouse line, and both of these lines retained remarkable memory not only at a young age, but also in the aging process.
A Hobbie-J line rat and a Doogie line mouse.
"This is another proof that the NR2B gene and its product are a universal link necessary for memory formation," says Dr. Joe Z. Joe Z. Tsien, one of the directors of the MCG Brain & Behavior Discovery Institute and the lead authors of the study.
The discovery also points to NR2B as a target for drugs designed to improve the memory of both healthy people and patients suffering from neurodegenerative diseases such as Alzheimer's disease and mild forms of dementia.
The NR2B protein belongs to the NMDA receptor family, which are tiny controlled pores in the outer membrane of a neuron through which charged ions pass, necessary for communication of nerve cells with each other. Dr. Tsien calls NR2B the "juvenile" form of the receptor, because, the scientist explains, in the process of growing up, the number of NR2B receptors on the membranes of nerve cells decreases, and they give way to another form of the receptor – NR2A.
Compared to NR2A, the pore formed by NR2B in the membrane remains in this state for about one hundred milliseconds longer when opened, allowing charged ions to move from the environment to the cell and back more actively. This is enough to significantly improve learning ability and memory. This, according to Dr. Tsien, is the reason that young people are much more capable in learning than the elderly. The configuration of the receptor determines the time during which "the door between neurons will remain open, and also limits the speed of information exchange."
Hobby-Ji rats outperformed normal Long Evans rats not only in relatively simple, but also in very complex tests requiring associative thinking from the animal. However, there were limits to the "super-rats". For example, in a test where animals were asked to choose a path to a piece of chocolate in a maze: animals of both lines coped with a repeated task if only one minute passed after completing the first one, after three minutes only Hobby-Ji rats remembered the correct path, and after five minutes the rats of both lines forgot the task. "We will never make mathematicians out of them. No matter what, they're just rats," says Dr. Tsien, noting that when it comes to really complex tasks, brain size matters.
This is one of the reasons why scientists want to continue research in this area: to see how the increased production of NR2B in more highly developed organisms, such as dogs and, possibly in the future, humans, affects thinking abilities. Also, Dr. Tsien and his colleagues are starting research aimed at finding out whether it is possible with the help of magnesium – a mineral component contained in nuts, beans and green vegetables such as spinach – to repeat the results obtained through the genetic modification of NR2B. Magnesium blocks NMDA receptors, as a result of which the cell begins to actively produce a more effective NR2B receptor to compensate for the loss of electrical impulses.
Hobby-Ji and Doogie lines, as the researchers have shown, can also be obtained using another genetic modification, enhancing the expression of CaMKII, a common NMDA receptor activator protein. In October 2008, a report appeared in the journal Neuron that with the help of CaMKII modifications, it is possible to both erase and return memories.
"We need to understand how universal this mechanism is," says Dr. Tsien, arguing about the connection between memory improvement and increased production of NR2B, "the results obtained on an isolated cell line or on animals cannot be so easily applied to other living systems until appropriate experiments are carried out." He adds that the failures of new drugs and other frustrations stem precisely from a lack of scientific evidence.
The results of the work are briefly described in the press release of the Medical College of Georgia: Smart rat "Hobbie-J" produced by over-expressing a gene that helps brain cells communicate.
Original article: Wang et al. Genetic Enhancement of Memory and Long-Term Potentiation but Not CA1 Long-Term Depression in NR2B Transgenic Rats. PLoS ONE, 2009; 4 (10).
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Remedium
22.10.2009