Saturday, January 29, 2011

Researchers Identify Potential Therapeutic Target For Improving Long-Term Memory

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Researchers from Mount Sinai School of Medicine have identified a therapy that may enhance memory and prevent the loss of long-term memory. The research is published in the January 27th issue of Nature.

Led by Cristina Alberini, PhD, Professor of Neuroscience at Mount Sinai, the research team evaluated how a protein called insulin-like growth factor II (IGF-II), a gene expressed during brain development that declines with aging, impacts memory formation and retention.

IGF-II is enriched in the adult brain in several areas, including the hippocampus and cortex, which are known to be important for memory formation. Researchers injected the hippocampus of rats with the protein and found that IGF-II significantly improved long-term memory. The team also found that IGF-II levels increased after learning, and that when that increase was blocked long-lasting memories could not form.

"The implications of these data are far-reaching and give us new clues about how to investigate memory loss and forgetfulness in people with cognitive impairment, like those with Alzheimer's disease, stroke, or dementia," said Dr. Alberini.

Prior to this study, very little, if anything, was known about IGF-II in adult brain functions. The researchers tested the impact of injecting IGF-II into rats after "inhibitory avoidance learning," in which the rats learn to avoid an unpleasant experience. They found that compared to control groups, the rats injected with IGF-II had a much stronger memory retention. In addition, the rats maintained an elevated memory for several weeks, while the control group showed diminished memory over the same period of time.

In collaboration with Robert Blitzer, PhD, Associate Professor of Pharmacology and Systems Therapeutics and Psychiatry at Mount Sinai, the research team also evaluated the impact of IGF-II at the cellular level. They found that IGF-II had an impact on long-term potentiation (LTP). LTP is a type of synaptic plasticity, or the change in strength of the points of contact between nerve cells, that is believed to be critical for long-term memory formation. Dr. Blitzer and his team found that IGF-II promoted stable LTP, strengthening signal transmission between nerve cells and maintaining it for a longer period of time.

"This study is the first step to understanding the benefits of IGF-II," said Dr. Alberini. "We have identified some of the mechanisms associated with this effect and look forward to further studying them and exploring the clinical relevance of IGF-II."

This study is supported by a grant from the National Institute of Mental Health. In addition to Drs. Alberini and Blitzer, co-authors from Mount Sinai's Department of Neuroscience include Dillon Chen, MD/PhD candidate; Sarah Stern, graduate student, and Dhananjay Bambah-Mukku, MD/PhD candidate, and Gabriella Pollonini, a Senior Scientist all with Dr. Alberini in the department of Neuroscience, and Bernadette Saunier-Rebori, PhD, a postdoctoral fellow in the department of Pharmacology and Systems Therapeutics, is also a co-author.

Mount Sinai Medical Center
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