Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation provides $2 million for study of cellular events that precede Alzheimer’s

SAN ANTONIO (Feb. 4, 2015) — The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation is giving $2 million to further Alzheimer’s disease research at The University of Texas Health Science Center at San Antonio.

Martin Paukert, M.D., assistant professor of physiology in the School of Medicine, is the principal investigator of the five-year grant. Dr. Paukert and his team are studying activities in the brain that may take place long before Alzheimer’s disease symptoms are observed.

One of the earliest sites of noticeable neurodegeneration is a brain stem structure called the locus coeruleus. This structure has a major influence on the entire central nervous system because it delivers norepinephrine, a neurotransmitter associated with attention or arousal. Initial triggers of Alzheimer’s disease may include less norepinephrine release, and fewer norepinephrine-dependent calcium spikes in cells called astrocytes. While astrocytes are the major support cells for neurons, in Alzheimer’s this relationship appears to be somehow affected, causing the death of neurons.

Dr. Paukert’s team is measuring calcium signals from astrocytes in real time while mice walk on tiny treadmills. “The hope is that we can use these signals as a readout of how much pharmaceutical manipulation is necessary to normalize norepinephrine signaling, and to see whether this intervention slows the progression of Alzheimer’s disease,” Dr. Paukert said.

The team will develop mouse models in which genes can be altered to produce Alzheimer’s-like effects. “The mice would be halfway to Alzheimer’s when we stop the genetic manipulations,” Dr. Paukert said. “We want to know whether the brain, including its support cells, possesses the ability to evade further damage.”

An important contribution to the studies will be the expertise of Manzoor Bhat, Ph.D., professor and chairman of the Department of Physiology, in establishing mouse models, and the expertise of Veronica Galvan, Ph.D., assistant professor of physiology and investigator with the Barshop Institute for Longevity and Aging Studies, in relating cellular changes to effects on Alzheimer’s- like memory deficits. Dr. Bhat occupies the Zachry Foundation Distinguished Chair in Neurosciences at the Health Science Center.

Dr. Paukert joined the Health Science Center in December 2013 from the Johns Hopkins University School of Medicine in Baltimore. “He represents a new generation of neuroscientists, who not only use but develop state-of-the-art, cutting-edge technology to address fundamental questions that go to the heart of neurobiological diseases in a living animal,” Dr. Bhat said.

“The Paukert lab is in its early phases in San Antonio, and funding from The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation will have a major impact on how quickly they can get the animal models established to address the central questions related to the early onset and progression of Alzheimer’s disease in real time, and in the future this will allow exploration of new avenues for therapeutic intervention,” Dr. Bhat said.


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