Fat Molecules Make Bigger Brains, Say Scripps Research Scientists
By Jason Socrates
A team of scientists at The Scripps Research Institute is
publishing a study in an upcoming issue of the journal Nature
Neuroscience that describes the effects of a particular
phospholipid molecule on the development of mammalian brains.
Phospholipids, molecules of fat with a charged head on one
end, are commonly found in biological organisms and are generally
regarded as essential structural components of cells. Bilayers
of phospholipids are the primary component of cellular membranes,
for instance, those essential barriers that define the boundaries
of cells and keep the molecules inside a cell separated from
those outside a cell.
But lipids apparently do more than just form barriers.
In their study, the Scripps Research scientists examined
the effect of molecules of a phospholipid called lysophosphatidic
acid (LPA) on developing brains in murine models. They found
that LPA can act as a signal that induces neurogenesisthe
formation of new neurons. Previously scientists believed that
growth factors and other proteins largely controlled neural
development and neurogenesis.
"Fat [molecules] have new roles that we are only beginning
to understand," says Scripps Research Professor Jerold Chun,
who is a member of The Helen L. Dorris Institute for the Study
of Neurological and Psychiatric Disorders of Children and
Adolescents at Scripps Research. "They potentially have profound
effects on brain development."
The work is significant because neural generation in early
development predestines an organism for what happens later
in life. The work may help clinicians and scientists understand
some of the many diseases that arise from developmental defects
that may be related to LPA signaling. Several childhood mental
disorders and certain types of schizophrenia, for instance,
are believed to be developmental in origin. The work may also
help clinicians understand how to control stem cell differentiationan
important step for stem cell therapy.
A Wrinkle in Mind
Chun and his colleagues have been looking at what controls
the formation of the cerebral cortex, the part of the brain
that is believed to be involved in higher functions, like
memory, cognition, and the interpretation of sensory input.
The vast majority of these cerebral cortex neurons are generated
before birth, and Chun and his colleagues, postdoctoral fellows
Marcy Kingsbury and Stevens Rehen, along with graduate students
James Contos and Christine Higgins, wanted to know what signals
controlled this process in early development.
A few years ago, their study of LPA led them to identify
the first cellular receptor to which it binds. Chun and his
colleagues discovered that when LPA binds to this receptor
in the embryonic brain, the result is a brain that shows a
vastly increased number of neurons in the cerebral cortex.
Remarkably, LPA induces folds in the brain. When developing
brains are exposed to LPA, the brains spontaneously form the
gyrated structures that are characteristic of higher mammals,
like humans. These gyrations increase the surface area of
the cerebral cortex that is believed to be essential to higher
functions like intelligence and reasoning, which are characteristic
of humans and other primates. Such gyrations are not normally
seen in the brains of lower mammals, like mice.
Interestingly, this neuronal increase works not by causing
neuronal progenitor cells in the brain to proliferate and
then become neurons, as one might expect, but by a new mechanism
whereby the neuronal progenitor cells that normally would
die are prevented from dying and other neuronal progenitor
cells are forced to divide prematurely.
The article, "Enhanced Cerebral Cortical Growth and Folding
by Non-Proliferative Effects Of Lysophosphatidic Acid" was
authored by M. A. Kingsbury, S. K. Rehen, J. J. A. Contos,
C. M. Higgins, and J. Chun and appears in the Advance Online
Publication edition of the journal Nature Neuroscience
on November 16, 2003. See: http://dx.doi.org/10.1038/Nn1157.
The article will appear in print later this year.
The work was supported by the Helen L. Dorris Institute
for the Study of Neurological and Psychiatric Disorders of
Children and Adolescents at Scripps Research and by grants
from the National Institutes of Mental Health.