Tuesday, October 25, 2011

MIT researchers grow nerve connections; may lead to brain disease treatments

By Lori Valigra, Mass High Tech correspondent

MIT scientists have devised a technique to grow nerve connections in a lab dish with the hope that one day the discovery could lead to new drugs to treat neurological disorders including autism and Alzheimer’s disease, according to information provided by MIT.

The idea behind the technique is to strengthen the synapses, or connections between the brain’s nerve cells or neurons, to treat brain diseases and the age-related decline of brain function. Each of the brain’s 100 billion neurons forms thousands of synapses with other neurons to rapidly share information, coordinate activities and achieve learning and memory. Breakdowns in the connections have been linked to neurological disorders and cognitive declines during normal aging.

The MIT research team devised a technique to grow synapses between cells in a lab dish under controlled conditions. They said that this may enable rapid, large-scale screens for potential new drugs. They have already identified several compounds that can strengthen synapses. They described their findings in the Oct. 25 online edition of Nature Communications. Such drugs could help compensate for the cognitive decline seen in Alzheimer’s, said Mehmet Fatih Yanik, associate professor of electrical engineering at MIT and leader of the research team that published the paper.

The lead author of the study was MIT postdoc Peng Shi. Other authors are MIT graduate students Mark Scott and Zachary Wissner-Gross; Stephen Haggarty, Balaram Ghosh and Dongpeng Wan of Harvard University; and Ralph Mazitschek of Massachusetts General Hospital, who developed and analyzed the potential drug compounds screened in the study.

At a synapse, a neuron sends signals to one or more cells by releasing chemicals called neurotransmitters, which in turn influence the recipient cell’s activity. To date, scientists have been able to induce neurons grown in a lab dish to form synapses, but this usually produces a jumble of connections that is difficult to study.

In the new MIT technique, presynaptic neurons that send messages across a synapse were grown in individual lab dish compartments. The compartments have one opening into a tiny channel that leads to another compartment. The presynaptic neuron sends its long axon (a part of the neuron that transmits impulses away from the cell’s body) through the channel into the other compartment, where it can form synaptic connections with a grid of cells. “That way we can induce synapses in very well-defined positions,” Yanik said in a statement.

The researchers can create hundreds of thousands of synapses in one lab dish and then use them to test potential drug compounds. The technique can detect changes in synaptic strength with 10 times more sensitivity than existing methods, the researchers claimed.

In their study, the researchers created and tested variants of an enzyme known as an HDAC (histone deacetylase) inhibitor that control how tightly DNA is wound inside the cell nucleus. That, in turn, determines which genes can be copied and expressed. HDAC inhibitors loosen DNA coils and reveal genes that had been turned off. They are now being pursued as potential treatments for Alzheimer’s and other neurodegenerative diseases.

The MIT researchers’ goal was to find HDAC inhibitors to turn on genes that enhance synaptic connections. To determine which of them had the strongest effects, they measured the amount of synapsin, a protein in the presynaptic neurons. They found several HDAC inhibitors that strengthened synapses, with the best one improving synapse strength by 300 percent, according to MIT.

In the future, this technique could be used to examine the connections between specific types of neurons from different regions in the brain, such as those thought to be impaired in people with autism. Yanik plans to make the technology available to other research groups interested in doing such studies, according to MIT.