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Brain synapse formation linked to proteins, Stanford study finds

dish form synapses. What wasn't clear is which proteins, exactly, are responsible for the new synapses and whether glia perform the same role in the developing brain. The Cell paper addressed these questions.

Barres and his team found that when they added various glial proteins to neurons grown in a lab dish without glia, only two proteins, called thrombospondins, encouraged new synapses to form. However, the synapses aren't completely normal. The synapse is made from two neurons-one that sends the message and one that receives the message. On the sending side, the synapse appears normal, but the receiving end isn't able to detect signals. Barres said other as yet unidentified signals from glia are necessary to form fully functional synapses.

When the group created mice that lacked the two thrombospondins they found 40 percent fewer synapses on average than the normal counterparts.

These thrombospondins' role of encouraging synapses to form makes sense, given when they are present in the brain: Barres and his group found them in the brains of developing mice during the time that the brain is actively making new synapses.

Interestingly, recent studies have found that one of the two thrombospondins is found at far higher levels in adult human brains than in adult monkey brains, possibly suggesting a key difference in the two animals' ability to form new synapses.

Barres said the thrombospondins they studied are just two of five related proteins. So far it hasn't been possible to eliminate all five thrombospondins in mice, but he suspects what few synapses the mice eked out were thanks to the remaining thrombospondins or perhaps other glial proteins. "Had we been able to knock out all five we might have seen even more synapse loss," Barres said.

Figuring out how and why new synapses form could be a boon for doctors treating people with brain damage. "If we deliver thrombospondins in the adult brain we co
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Contact: Amy Adams
amyadams@stanford.edu
650-723-3900
Stanford University Medical Center
10-Feb-2005


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