In a new study conducted by the Sagol Department of Neurobiology at the University of Haifa and published recently in the Journal of Neuroscience, researchers report that they've found a way to improve memory by manipulating a specific molecule that is known to function poorly in old age and is closely linked to Alzheimer’s disease.
The researchers even succeeded, for the first time, in manipulating the molecule’s operations without creating any cognitive impairment.
“We know that in Alzheimer’s, this protein, known as PERK, doesn't function properly. Our success in manipulating its expression without causing any harm to the proper functioning of the brain paves the way for improving memory and perhaps even slowing the pathological development of diseases like Alzheimer’s,” said Prof. Kobi Rosenblum, who heads the lab in which the research was done.
Previous studies at the University of Haifa and other labs throughout the world had shown that the brain’s process of formulating memory is linked to the synthesis of proteins; high rates of protein production will lead to a strong memory that is retained over the long term, while a slow rate of protein production leads to weak memories that are less likely to be impressed on a person’s long-term memory and thus forgotten.
In the current study, the researchers, Dr. Hadile Ounallah-Saad and Dr. Vijendra Sharma, both of whom work in Prof. Rosenblum’s lab at the Sagol Department of Neurobiology, sought to examine the activity of a protein called elF2 alpha, a protein that’s known as the “spigot” or regulator that determines the pace of protein synthesis in the brain during memory formation.
From earlier studies the researchers knew that there are three main molecules that act on the protein and either make it work, or stop it from working. During the first stage they sought to determine the relative importance and the task of each one of the molecules that control the activity of efF2 alpha and as a result, the ability to create memories. After doing tests at the tissue and cell levels, the researchers discovered that the main molecule controlling the efF2 alpha’s activity was the PERK molecule.
“The fact that we identified the PERK as the primary controller had particular significance,” said Dr. Ounallah-Saad. “Firstly, of course, we had identified the dominant component. Secondly, from previous studies we already knew that in generative diseases like Alzheimer’s, PERK performs deficiently. Third, PERK acts on various cells, including neurons, as a monitor and controller of metabolic stress. In other words, we found a molecule that has a major impact on the process of creating and formulating memory, and which we know performs deficiently in people with Alzheimer’s disease.”
During the second stage of the study, the researchers sought to examine whether they could manipulate this molecule in rats in a way that would improve memory. To do this they used two accepted methods, one using a drug called a small-molecule inhibitor and the other making a genetic change to the brain cells using a type of virus also used in gene therapy.
After paralyzing PERK’s activity or reducing its expression through gene therapy (which was done with the help of Dr. Efrat Edry, of the University’s Center for Gene Manipulation in the Brain), the researchers measured a 30% increase in the memory of either positive or negative experiences. The rats also demonstrated improved long-term memory and enhanced behavioral plasticity, becoming better able to “forget” a bad experience. In other words, on a behavioral level it was clear that manipulating PERK by either of two methods improved memory and cognitive abilities.
When the researchers examined the tissues on a cell and molecular level, the discovered that the steps they’d taken had indeed stopped the expression of PERK, which allowed the “spigot” – the elF2 alpha protein – to perform better and increase the pace of protein synthesis. Even more, there was a clear correlation between memory function and the degree to which PERK was suppressed; the more efficiently PERK was suppressed, the better the memory function.
But the researchers faced another problem. Previous studies that had manipulated PERK in general in genetically engineered animals led to fixated behavior. “The brain operates in a most sophisticated fashion, with each action closely linked to many other actions,” said Dr. Ounallah-Saad. “In our study we succeeded in maintaining such control of the PERK that it didn't influence the retrieval of existing memories, or do anything other cognitive damage.”
“With this study we proved that we are capable of strengthening the process of protein synthesis in the brain and of creating stronger memories that last a long time,” said Prof. Rosenblum. “The moment we did this by manipulating a molecule that we know performs deficiently in people with Alzheimer’s and is linked to the aging process, we have paved the way for the possible development of drugs that can slow the progress of incurable diseases like degenerative brain conditions, Alzheimer’s chief among them.”
For further details:
Division of Communications and Media Relations | University of Haifa
Media Relations | University of Haifa
Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung
High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences