U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
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National Institute on Drug Abuse (NIDA) http://www.nida.nih.gov/
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Thursday, February 10, 2005
12:00 p.m. ET
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RESEARCH IDENTIFIES PROTEINS CRUCIAL TO CONSTRUCTION OF BRAIN'S
INFORMATION SUPERHIGHWAY
Communication in the brain travels from one nerve cell to another
through critical connections called synapses. These neuron-to-neuron
junctions form early in brain development, and their construction was
thought to be guided by the nerve cells themselves. Now, investigators
supported by the National Institute on Drug Abuse (NIDA), National
Institutes of Health, have discovered that cells called glia, known to
provide support for neurons in the mature brain, also play a crucial
role in formation of synapses during the surge of development following
birth. This key insight into the process of normal synapse development
may lead to improved treatment of conditions such as drug addiction and
epilepsy, which are characterized in part by too many synapses. The
research, led by Dr. Ben Barres of Stanford University School of
Medicine in Stanford, California, is reported in the February 11, 2005
issue of the journal "Cell".
"Synapses are the key connections between cells in the brain. We know
that drugs alter these connections, and that the developing brain is
vulnerable to addictive drugs' disruption of normal communication," says
NIDA Director Dr. Nora D. Volkow. "Compounds that direct synapse
formation may offer a therapeutic option for people fighting drug
addiction or other neurologic conditions."
Glia account for 90 percent of the cells in a mammalian brain, but until
recently scientists focused mainly on the supportive role that glial
cells play in helping mature neurons survive. Dr. Barres, along with
Stanford postdoctoral fellows Dr. Karen Christopherson and Dr. Erik
Ullian, developed a method for growing neurons in a laboratory without
glial cells. Then they isolated proteins produced by glial cells and
observed the effect when they added the proteins to a culture of
neurons. Two of the proteins, thrombospondin 1 and 2, led to the
development of synapses -- albeit functionally incomplete ones.
The synapses that developed in Dr. Barres' laboratory dish in the
presence of thrombospondin were able to transmit signals but were unable
to receive them. In other words, the neuron transmitting the signal is
able to secrete a chemical messenger called a neurotransmitter but the
neighboring neuron receiving the signal is unable to detect the presence
of the neurotransmitter. Because completely functional synapses occur in
the presence of glia, "we know that glia produce at least one other
protein, which we have not yet identified, that is necessary to produce
a fully functional synapse," Dr. Barres says. This yet unidentified
protein enables the receiving neuron to detect the neurotransmitter sent
from the neuron transmitting signal when synapses form.
To help confirm the role of the thrombospondins in synapse development,
the scientists next developed a strain of mice that lacked the ability
to produce thrombospondins 1 and 2; the brains of these mice had 40
percent fewer synapses than normal mice. Interestingly, glia only
secrete these thrombospondins early in brain development, concurrent
with the normal formation of synapses. These new findings raise the
possibility that the relatively poor ability of the adult brain to form
new synapses may be due to the low levels of the glial thrombospondins.
"Fully understanding the contribution made by glial thrombospondins
could make possible the development of thrombospondin-based therapies to
stimulate and direct synapse formation," notes Dr. Volkow.
The National Institute on Drug Abuse is a component of the National
Institutes of Health, U.S. Department of Health and Human Services. NIDA
supports more than 85 percent of the world's research on the health
aspects of drug abuse and addiction. The Institute carries out a large
variety of programs to ensure the rapid dissemination of research
information and its implementation in policy and practice. Fact sheets
on the health effects of drugs of abuse and information on NIDA research
and other activities can be found on the NIDA home page at
http://www.drugabuse.gov.
##
This NIH News Release is available online at:
http://www.nih.gov/news/pr/feb2005/nida-10.htm.
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