PA) - Researchers at the University of Pennsylvania School
of Medicine have demonstrated that star-shaped glial cells
in the brain called astrocytes are directly involved in regulating
communication between neurons. A central finding of the study is
that astrocytes modulate the level of a signaling molecule called
adenosine, which is thought to be important in controlling wake-to-sleep
transitions and epileptic seizures.
“This finding may cause neuroscientists to radically alter
their view of the role of astrocytes as merely supportive to one
of actively communicating with and instructing neurons,” states
senior author Philip G. Haydon, PhD, Professor
of Neuroscience. “Astrocytes are not just the ‘kitchen
cells’ of the brain, providing nutritional support, but instead
also help the neurons talk to each other.” Haydon and colleagues
published their results in last week’s issue of Science.
The central nervous system, which includes the brain and spinal
cord, is composed of specialized cells called neurons that send
out and receive chemical signals called neurotransmitters across
a space called the synapse. This process results in transmission
of a nerve impulse. Historically, the glial cell or astrocyte was
considered to be a support cell and to play no active role in regulating
nerve impulse transmission. However, recent research by Haydon and
other investigators has indicated that glial cells do produce chemical
transmitters called gliotransmitters and that these chemical signals
are recognized by the neurons. The studies that have shown capability
were conducted on isolated nerve cells or on slices of brain tissue.
In this most recent study, the researchers made genetic manipulations
to glial cells in live mice, thus directly demonstrating how astrocytes
function in the brain. The mice were engineered to produce a protein
called SNARE in their astrocytes. When the SNARE protein was produced,
the amount of adenosine decreased.
When adenosine accumulated, nerve impulses were suppressed and could
not be transmitted across the synapse. This helps explain why high
adenosine levels can suppress epileptic seizures.
In contrast, low levels of adenosine increased the transmission
of nerve impulses. The modulation of neuronal activity through the
regulation of the level of adenosine in the synapse may explain
the nature of wake-to-sleep transitions during periods of drowsiness.
“The next step is to study the behavior of these mice during
manipulation of adenosine levels in the brain,” says Haydon.
The study was a collaboration between Haydon and Stephen Moss at
Penn and Ken McCarthy, University of North Carolina, Chapel Hill.
The lead author was Olivier Pascual, a post-doctoral fellow in Penn’s
Department of Neuroscience. Co-authors are Kristi Casper, Cathryn
Kubera, Jing Zhang, Raquel Revilla-Sanchez, Jai-Yoon Sul and HajimeTakano.
This study was funded by the National Institute of Neurological
Disorders and Stroke and the National Institute of Mental Health.
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