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Protein stimulates key link between nerve cells, suggesting possible target for mental retardation and nerve regeneration therapies

be mastered and walking to be relearned following a stroke. But without the synapses that allow the chemical signal's transmission from one nerve cell to the next, glutamate has no more luck in communicating its messages than a train has luck in reaching its destination without tracks to follow.

During synaptic transmission, nerve cells release thousands of neurotransmitters from their nerve terminals at once. The messengers diffuse across a synaptic cleft to corresponding receptors on a target cell, and prompt a response in that cell that is then transmitted to another cell and yet another, ultimately causing a wave of reaction in the brain.

Some neurotransmitters, such as GABA, carry inhibitory signals, reducing excitation and anxiety in the brain, and others, such as dopamine and serotonin, modulate the activity of neural circuits to influence mood and sleep. The millisecond relay of glutamate to thousands of nerve cells sparks the brain into high activity.

Mental retardation is associated with a loss of the dendritic spines on post-synaptic neurons that play a role in receiving glutamate messages. As the study shows that PSD-95 increases the number and size of these spines, gene therapy could prove effective in stimulating the growth of the spines and thus treating the disease. Likewise, using PSD-95 gene therapy to stimulate the maturation of glutamate receptors could be used to regenerate nerves following stroke or spinal cord injury.

On the flip side, when nerve cell receptors that receive glutamate become overactive and thus receive too much glutamate - as occurs following stroke and in such neurodegenerative diseases as Alzheimer's disease -- brain damage occurs.

Much research is aimed at treating this so-called excito-toxicity by blocking the glutamate receptor. But identifying a way to disrupt the synapses that allow communication of glutamate from one nerve cell to another could provide an alt
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
16-Nov-2000


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