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People suffering from dementia – and other problems with deteriorating memories
– could eventually benefit from a new understanding of a brain enzyme named
protein kinase M zeta (PKMzeta).
The Weizmann Institute of Science and
New York’s SUNY Downstate Medical Center have successfully manipulated the
enzyme in rats to improve memory.
The work was chronicled by Downstate,
where Prof. Toss Sacktor, a grantte of the US National Institute of
Health’s National Institute of Mental Health, conducts research. The results
generated great interest after it was published over the weekend in the journal
By manipulating the enzyme, the team found they could erase
long-term memories, and perform the opposite feat: enhance memories that had
been erased long ago.
“Our study is the first to demonstrate that, in the
context of a functioning brain in a behaving animal, a single molecule, PKMzeta,
is both necessary and sufficient for maintaining longterm memory,” Sacktor
Unlike other recently discovered approaches to memory enhancement,
the PKMzeta mechanism appears to work any time.
It is not dependent on
exploiting time-limited windows, when a memory becomes temporarily fragile and
changeable – like just after learning and upon retrieval – which may expire as a
memory grows older, said Sacktor.
“This pivotal mechanism could become a
target for treatments to help manage debilitating emotional memories in anxiety
disorders, and for enhancing faltering memories in disorders of aging,” said
NIMH Director Dr. Thomas Insel.
In studies going back five years, Dudai
and Sacktor showed that even weeks after rats learned to associate a nauseating
sensation with saccharin – and shunned the sweet taste – their sweet tooth
returned within a couple of hours after receiving a chemical that blocked the
enzyme PKMzeta in the brain’s outer mantle, where long-term memories are
In the new study, they paired genetic engineering with the same
aversive learning model to both confirm the earlier studies, and demonstrate
that by increasing PKMzeta, the opposite effect transpired.
harnessed a virus to infect the neocortex with the PKMzeta gene, resulting in
overexpression of the enzyme and memory enhancement.
introducing a mutant inactive form of the enzyme, that replaced the naturally
occurring one, erased the memory – much as the chemical blocker
These effects applied generally to multiple memories stored in the
targeted brain area – raising questions about how specific memories might be
targeted in future therapeutic applications.
Indeed, the researchers
turned up a clue that may hold the beginning of an answer.
explanation of the memory enhancement is that PKMzeta might go to some synapses,
or connections between brain cells, and not others,” Sacktor said.
“Overexpressed PKMzeta may be selectively captured by molecular tags that mark
just those brain connections where it’s needed – likely synapses that were
holding the memory from the training.”