Memory-boosting chemical found in mice

Researchers claim to have discovered a new memory-boosting chemical in mice, a finding that could pave way for drug targets to improve memory in humans.
In one memory test, normal mice were able to relocate a submerged platform about three times faster after receiving injections of the potent chemical than mice that received sham injections, researchers said.
The mice that received the chemical also better remembered cues associated with unpleasant stimuli - the sort of fear conditioning that could help a mouse avoid being preyed upon.
"It appears that the process of evolution has not optimised memory consolidation, otherwise I don't think we could have improved upon it the way we did in our study with normal, healthy mice," senior study author, Peter Walter from the University of California, San Francisco (UCSF) said.

The memory-boosting chemical was singled out from among 100,000 chemicals screened for their potential to perturb a protective biochemical pathway within cells that is activated when cells are unable to keep up with the need to fold proteins into their working forms.
Researcher Carmela Sidrauski discovered that the chemical acts within the cell beyond the biochemical pathway that activates this unfolded protein response, to more broadly impact what's known as the integrated stress response.

In this response, several biochemical pathways converge on a single molecular lynchpin, a protein called eIF2 alpha.
"Among other things, the inactivation of eIF2 alpha is a brake on memory consolidation," Walter said, perhaps an evolutionary consequence of a cell or organism becoming better able to adapt in other ways.

Turning off eIF2 alpha dials down production of most proteins, some of which may be needed for memory formation, Walter said. Its inactivation also ramps up production of a few key proteins that help cells cope with stress.
Study co-author Nahum Sonenberg, of McGill University previously linked memory and eIF2 alpha in genetic studies of mice.
The chemical integrated stress response inhibitor (ISRIB) counters the effects of eIF2 alpha inactivation inside cells, the researchers found.
"ISRIB shows good pharmacokinetic properties (how a drug is absorbed, distributed and eliminated), readily crosses the blood-brain barrier, and exhibits no overt toxicity in mice, which makes it very useful for studies in mice," Walter said.

These properties also indicate that ISRIB might serve as a good starting point for human drug development, said Walter.
The study was published in the journal eLife.