Researchers find the adhesions that build the brain's networks

While the brain's neurons are often the focus of scientific attention, astrocytes, literally star-shaped cells, are becoming increasingly important in helping a brain become well organized. Particularly, astrocytes (which make up about half of the human brain's mass) seem to be able to direct the formation of synapses. These are the connections between neurons that are formed as we learn and recall. Researchers at UNC and Duke have discovered a key protein that is involved in communication and coordination among astrocytes during the building of synapses. This molecule, called hepaCAM is missing from astrocytes. They are less sticky than they should be and stick more to themselves than to form connections with other astrocytes. This discovery was made in experiments on mice that had the gene for hepaCAM removed from their astrocytes. It is an important clue to understanding brain disorders such as cognitive decline and epilepsy. This work is published in Neuron on June 24, 2009. Megalencephalic Leukoencephalopathy (MLC), a rare disorder, is also known to have been caused by a mutation of the hepaCAM genes. This work may provide clues as to what might be wrong. MLC is a progressive developmental disorder that causes macrocephaly (large head), swelling of brain's white matter, intellectual disabilities, epilepsy, and other complications. To see the effects of hepaCAM, we removed astrocytes selectively. Senior author Cagla Eroglu, an associate Professor of Cell Biology at Duke University School of Medicine, said that "we kind of made the cells introverts" by removing it from astrocytes. They were normally able to reach out to others, but they stopped using hepaCAM and started hugging themselves instead. Eroglu stated that astrocytes can make connections to their neighbors to create a network. A functional astrocytic network is necessary to create a functional brain. Researchers focused on hepaCAM through the identification of genes in astrocytes that are active and have been linked to brain dysfunction. They partnered with another research group at the University of Barcelona to study hepaCAM. That group was interested in the molecule's role in regulating the chloride signaling channels within astrocytes. The Duke team found that astrocytes containing hepaCAM were able to cause a synaptic network to become too excited and less dampened. Katie Baldwin, the first author of the study and assistant professor of cell biology at North Carolina's University of Chapel Hill, said that the strongest effect was on inhibitory synapses. "You are putting the inhibition down, and the excitation up. This could be a sign of epilepsy. Baldwin did this research as a postdoctoral researcher at Eroglu's laboratory. She plans to continue exploring these questions in her UNC lab. There, she will test whether hepaCAM deficient mice exhibit stress and anxiety, which are signs of autism spectrum disorders. To see if it has any effects, they may also try to reintroduce disease-mutated versions of the protein to mice who were not born with it. Baldwin stated that hepaCAM interacts with itself between two astrocytes but doesn't know the synapse with which it is interacting. We don't yet know if the protein could interact with hepaCAM, which is also found within neurons. This research was funded by the U.S. National Institutes of Health, Foerster-Bernstein Family and The Hartwell Foundation.

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