Astrocytes modulate adenosine - thought to be important in controlling wake-to-sleep transitions and epileptic seizures

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.