Boosting SIRT1 in mice does not improve memory, but if gene is missing memory suffers

Tampa, FL (Aug. 9, 2010) – SIRT1, a protein expressed by neurons in the brain’s hippocampus region, is critical for learning and memory, yet presents a paradox, reports an international team of researchers from the University of South Florida, the University of Southern California, Harvard University Medical School, the National Institute on Aging at the National Institutes of Health, the Institutos Nacionales de Salud of Mexico, and the University of Ottawa.

The researchers found boosting natural levels of SIRT 1 in laboratory mice did not improve the animals’ memory and learning skills. However, mice lacking the SIRT 1 protein exhibited impaired learning and memory and also had neurological defects. A combination of behavioral, morphological, and electrophysiological models were used to analyze the effects of both SIRT1 deficiency and over expression.

Their findings are published in the current issue of the Journal of Neuroscience.

“Understanding how changes in the brain’s microcircuitry are related to alterations in the network of brain cell communication may lend significant new insight into how the absence of the SIRT1 gene can impact learning and memory in the test mice,” said study co-author Dr. Ronald Mervis, associate professor in the Department of Neurosurgery and Brain Repair at the University of South Florida.

Their test results also suggest that the case for supplementing a normal diet with sirtuin activators, a family of compounds targeted to activate SIRT1, may be weak.

“Research into the physiological functions of sirtuins in humans, particularly in aging, has been ongoing and intense,” said Dr. Mervis.

For example, many studies have shown that resveratol, a proposed ”anti-aging” sirtuin activator in red wine, does benefit some aspects of health, but has not prolonged the lives of normal laboratory mice. Resveratol has, however, been shown to improve the health and life span of mice fed a high-fat diet. Other studies have shown that the absence of SIRT1 protects neurons. The researchers concluded that there might be a “trade-off” between SIRT1 protection and toxicity that is essential for learning and memory.

“Our findings that the Sirt1 knockout mice exhibit a reduction of dendritic branching of an important class of neurons in the hippocampus – a critical component in memory circuits – would contribute to the loss of normal communication between neurons and could also help explain the memory deficits seen in these mice,” said Dr. Mervis. “Mice with normal and high levels of SIRT 1 expression exhibited regular synaptic plasticity and memory. We concluded that SIRT 1 is indispensible for normal learning, memory and synaptic plasticity in mice.”

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Funding for the research was provided by the National Institutes of Health; the Canadian Institutes of Health Research; the Ellison Medical Foundation, the intramural research program of the National Institute on Aging; and the Paul F. Glenn Foundation for Medical Research.

– About the Center of Excellence for Aging and Brain Repair –

The mission of the University of South Florida Center of Excellence for Aging and Brain Repair is to develop new therapeutic strategies to promote repair and regeneration of aging and diseased brain. Building on a foundation of excellence in basic and clinical research, the Center focuses on translating innovative ideas into industrial partnerships, educational and clinical services to address key needs of the community and those suffering from brain injury and disease.