$1.5 million in NIH funding awarded to UNR Med researcher to advance understanding of brain-degenerative diseases

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A photo of Robert Renden, Ph.D., assistant professor in the department of physiology and cell biology at UNR Med, in his lab.

Robert Renden, Ph.D., assistant professor in the department of physiology and cell biology at UNR Med is exploring how mitochondria support synaptic function in the healthy brain, in order to advance new approaches in the study of some diseases. Photo by Brin Reynolds/UNR Med.

Robert Renden, Ph.D., assistant professor in the department of physiology and cell biology at the University of Nevada, Reno School of Medicine (UNR Med) was recently awarded a competitive, three-year, $1.5 million grant from the National Institutes of Health (NIH) to identify pharmacological approaches for restoring brain energy production, in order to treat brain-degenerative diseases associated with aging.

Renden and Ruben Dagda, Ph.D., associate professor of cellular and molecular pharmacology and physiology, are working together to better understand how calcium waves and mitochondria support synaptic function in the healthy brain, and how these mechanisms change with age.

"We have a surprisingly poor understanding of how the brain maintains energy, especially at sites of neuronal communication, called synapses," says Renden. Synapses, communication points between brain cells, play a critical role in all cognitive processes, including learning and memory. Synapse dysfunction also play a crucial role in many brain disorders, including Alzheimer's disease.

"Neurons use a lot of energy, on demand," says Dagda. "Loss of energy flow results in disastrous consequences to brain function. Common examples are lack of oxygen supply causing unconsciousness within minutes, and low blood sugar (hypoglycemia), which alters behavior."

The grant funding will further Renden and Dagda's collaborative research into testing the effects of obstructing mitochondrial calcium uptake. Mitochondrial calcium is a key regulator of cellular energy production.

"There is evidence that many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are caused by alterations in calcium levels inside neurons and by dysfunction in mitochondria, one of the main sources for cellular energy," said Renden.

Dagda expanded that "as a consequence of mitochondrial dysfunction and calcium signaling, neurons do not produce the necessary energy from normal sources such as glucose, lipids and amino acids, to maintain healthy activity. They compensate by using alternative pathways of energy production. Over time, altered energy production in neurons causes a high level of stress in the brain and leads to a severe loss of neuronal circuits, a pathological process termed "brain atrophy."

"If we can find therapeutic ways to prevent neurons from undergoing an energetic crisis in the brain, we can prevent neurodegeneration in brain-degenerative diseases in patients before the onset of clinical symptoms," said Renden.

"We're very proud that the unique scientific approach spearheaded by one of our talented assistant professors, Dr. Robert Renden, is being recognized as having transformative potential by the NIH, as well as the National Science Foundation," said UNR Med Dean Thomas L. Schwenk, M.D. "The research is poised to make important contributions in how we think about the brain's function in both health and disease."

"The research led by Dr. Renden has significance for understanding how we can keep our brain healthy during normal aging and how to minimize cognitive changes that affect many older individuals," said Lucia Notterpek, Ph.D., associate dean for biomedical research at UNR Med.

The NIH is the largest public funder of biomedical research in the world, expanding the biomedical knowledge base by funding cutting-edge research and cultivating the biomedical workforce of today and tomorrow.

The University of Nevada, Reno School of Medicine's biomedical scientists are internationally recognized in the fields of neuroscience, infectious diseases, reproductive endocrinology, muscular dystrophy, cardiovascular physiology and gastrointestinal diseases, among other fields. UNR Med researchers have generated nearly $240 million in research funding over the past decade, supporting research that is changing science and enhancing the quality of life for many.

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The University of Nevada, Reno School of Medicine, Nevada's first public medical school, is a community-based, research-intensive medical school with a statewide vision for a healthy Nevada. Established in 1969, UNR Med is improving the health and well-being of all Nevadans and their communities through excellence in student education, postgraduate training and clinical care, research with local, national and global impact and a culture of diversity and inclusion.

Released: Tuesday October 13, 2020 @ 6:00 AM