Alzheimer's, Dementia & Mental Health
Memory Cocktail Envisioned as Way to Improve Memory,
Discovery of mechanism that stores memories in the
brain may open door to Holy Grail of memory neuroscience – a "smart
March 5, 2013 – Researchers are now envisioning a
“memory cocktail” with a combination of small molecules to improve
different aspects of memory formation to efficiently treat cognitive
disorders. They have discovered a mechanism – mTORC2 - by which memories
are stored in the brain.
Introductions at a party seemingly go in one ear
and out the other. However, if you meet someone two or three times
during the party, you are more likely to remember his or her name. Your
brain has taken a short-term memory - the introduction - and converted
it into a long-term one.
The molecular key to this activity is mTORC2
(mammalian target of rapamycin complex 2), according to researchers at
Baylor College of Medicine in an article that appeared online in the
"Memory consolidation is a fundamental process,"
said Dr. Mauro Costa-Mattioli, assistant professor of neuroscience at
BCM and corresponding author of the report.
"Memories are at the center of our identity. They
allow us to remember people, places and events for a long time, even a
lifetime. Understanding the precise mechanism by which memories are
stored in the brain will lead to the development of new treatments for
conditions associated with memory loss".
For the last five decades, neuroscientists have
known that making long-lasting memories is dependent on the ability of
brain cells (neurons) to synthesize new proteins. In their studies,
Costa-Mattioli and his colleagues found this new mechanism by which
memories are stored in the brain. The newly discovered mTORC2 regulates
memory formation by modulating actin fibers, an important component of
the architectural structure of the neuron.
"These actin fibers allow long-lasting changes in
synaptic strength and ultimately long-term memories," said Wei Huang, a
BCM graduate student and first author in the study.
Using genetically-engineered mice, the researchers
found that turning off mTORC2 in the hippocampus (a crucial region
required for memory formation) and surrounding areas allowed the animals
to have a normal short-term memory, but prevented them from forming
long-term memories. Similar to human patients with injury in the
hippocampus, these mutant mice were no longer able to form new
According to Costa-Mattioli's findings, mTORC2's
role is evolutionarily conserved and likely relevant to humans. Like
mTORC2-deficient mice, fruit flies lacking TORC2 show defective
long-term memory storage.
"Given that flies and mice last shared a common
ancestor 500 million years ago, it is quite remarkable and telling that
the function of mTORC2 in the regulation of memory is indeed
Dr. Gregg Roman, director
of the Biology of Behavior Institute at the
University of Houston,
who contributed to the fly experiments.
Form long-term memories
The Holy Grail of memory neuroscience and to a
certain extent, of industry efforts to produce a "smart drug," has been
the identification of molecules that promote the formation of long-term
memory, said Costa-Mattioli. "We therefore wondered whether by turning
on mTORC2 or even actin polymerization itself, we could form long-term
memories more easily," said Dr. Ping Jun Zhu, assistant professor of
neuroscience at BCM, co-first author and senior scientist in Costa-Mattioli's
The team has identified a small molecule (a drug)
that by activating mTORC2 and consequently actin polymerization enhances
not only the synaptic strength between nerve cells but also long-term
memory formation. In addition, the authors found that by directly
promoting actin polymerization, with a second drug, long-term memory is
generated more easily.
Costa-Mattioli's team has identified two
memory-enhancing drugs, but can they enhance memory in people? It is
perhaps too early to say.
Huang said, "mTORC2, as far as we know, is really a
new potential target for therapeutic treatments of human disorders. In
the next few years, I predict we will see a lot of studies focusing on
mTORC2 as a target."
Costa-Mattioli's short-term goals are to identify
human cognitive disorders in which mTORC2 activity is dysfunctional and
to see whether its restoration can return to normal impaired memory
function in aging or even Alzheimer's disease. But a small molecule
alone might not do the job. Similar to the treatments for HIV or cancer,
he believes that a combination of small molecules improving different
aspects of memory formation will be required to efficiently treat
"We should start thinking about an efficient
'memory cocktail' rather than a single 'memory pill.' One molecule alone
might not be enough. We may be years away from a decisive treatment, but
I believe we are definitely on the right path," he said.
Others who took part in this work include Hongyi
Zhou, Loredana Stoica and Mauricio Galiano, all of BCM, Krešimir
Krnjević of McGill University in Montreal, Canada; and Shixing Zhang of
the University of Houston.
Funding for this work came from the National
Institute of Mental Health (Grant MH 096816), the National Institute of
Neurological Disorders and Stroke (Grant NS 076708), The Searle Award
(Grant 09-SSP-211P), a Whitehall Award, The George and Cynthia Mitchell
Foundation, the National Institutes of Health (Grant MH091305) and a
Texas Norman Hackerman Advanced Research Program Award.
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