Now, keep up to date
with daily feeds of newly posted stories
about America's Seniors...click on the box
to the left
This
is Your Brain on Fatty Acids
Newswise — Saturated fats have a deservedly
bad reputation, but Johns Hopkins scientists
have discovered that a sticky lipid
occurring naturally at high levels in the
brain may help us memorize grandma’s recipe
for cinnamon buns, as well as recall how,
decades ago, she served them up steaming
from the oven.
The Hopkins team, reporting Oct. 29 in
Neuron, reveals how palmitate, a fatty acid,
marks certain brain proteins – NMDA
receptors – that need to be activated for
long-term memory and learning to take place.
The fatty substance directs the receptors to
specific locations in the outer membrane of
brain cells, which continually strengthen
and weaken their connections with each
other, sculpting and resculpting new memory
circuits.
Moreover, the researchers report, this fatty
modification is a reversible process, with
some sort of on-off switch, offering
possibilities for manipulating it to enhance
or even, perhaps, erase memory.
“Before now, no one knew that NMDA receptors
change in response to the addition of
palmitate,” says Richard Huganir, Ph.D.,
professor and director of the Solomon H.
Snyder Department of Neuroscience at Johns
Hopkins.
Scientists have known that a brain signaling
chemical called glutamate normally activates
NMDA receptors, allowing two neurons to
communicate with one another. However, they
were less certain what allowed this receptor
to assemble properly, or what caused it to
make its way to the synapse, the specialized
part of nerve cells where communication
takes place.
The discovery emerged from work with live
neurons in a dish, to which the scientists
first fed radioactive palmitate, then
separated out the NMDA receptors. By
tracking radioactivity on X-ray film, they
were able to determine that the fat had
attached to the NMDA receptors.
Next, the scientists put both normal and
altered NMDA receptors into non-brain cells
that don’t normally manufacture their own
NMDA receptors. By tracking the radioactive
fat, they were able to determine where on
the NMDA receptor the fat had attached.
Results showed that the NMDA receptor
undergoes “dual palmitoylation,” in two
different regions, each of which plays a
distinct role in controlling the fate of the
receptor in neurons. When the fat attaches
to the first region, it stabilizes the
receptor on the surface of neurons. When the
fat attaches to the second region, the
receptors accumulate inside neurons, perhaps
awaiting a signal to send them to synapses.
The researchers suspect that this could be
part of a quality control measure, assuring
that all the Lego-like protein subunits of
the receptor are put together properly.
“It is rapidly becoming clear that palmitate
regulates not only NMDA receptors, but also
other brain proteins at work during
signaling across synapses,” says Gareth
Thomas, Ph.D., a Howard Hughes Medical
Institute postdoctoral fellow at Hopkins.
The researchers suspect that if
palmitoylation fails, the result would be
learning and memory impairment because if
NMDA receptors don’t make their way to the
synapses – the specialized contact points
between cells across which chemical messages
flow – then communication between neurons is
compromised.
“This new modification of the NMDA receptor
deepens our molecular understanding of how
synapses are regulated and how memories
might be formed. It also reveals new
potential drug targets, such as the enzymes
that add or remove the palmitate,” Huganir
says. “If we could shift the balance of the
palmitoylation, then perhaps we could affect
and enhance learning and memory.”
This study was supported by research grants
from the National Institute of Mental Health
and the Howard Hughes Medical Institute.
Authors on the paper are Takashi Hayashi,
Gareth Thomas and Richard Huganir of Johns
Hopkins.
... ..
...
...