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2011 Grants - Rosi
Restoring Synaptic Plasticity in a Transgenic Rat Model of Alzheimer's Disease
Susanna Rosi, Ph.D.
University of California - San Francisco
San Francisco, California
2011 Investigator-Initiated Research Grant
One of the unique features of nerve cells is their ability to send rapid signals to other nerve cells through synapses, structures specialized for this purpose. The properties of synaptic signals can change in response to previous activity or other signals, a property known as plasticity. Synaptic plasticity accounts for at least part of the brain's ability to learn and remember.
Memory loss is a primary symptom of Alzheimer's disease, occurring with dysfunction of synapses and synaptic plasticity. The causes of synaptic dysfunction are unknown, but leading suspects include the protein fragment beta-amyloid and inflammation in the brain.
Susanna Rosi, Ph.D. and colleagues have been studying inflammation in the brain, focusing on the role of a hormone-like molecule known as tumor necrosis factor-alpha (TNF-alpha). Increased levels of TNF-alpha in the brain have been implicated in the inflammation that occurs during the early stages of Alzheimer's disease. Dr. Rosi's team plans to use a strain of rats that have been genetically modified to exhibit essentially all the pathologic features of human Alzheimer's disease. They will treat these rats with a drug known to inhibit the activity of TNF-alpha and determine if the treatment prevents the progression of Alzheimer's-like pathology in the brain.
The researchers will also use molecular techniques to study the activity of genes associated with synaptic plasticity, to determine if drug treatment restores the ability of brain synapses to perform this function vital to memory. These studies will probe the role of a key cause of brain inflammation and may identify a specific target for future therapies to prevent memory dysfunction in Alzheimer's disease.