Orly Lazarov, Ph.D.
Assistant Professor of Anatomy and Cell Biology, University of Illinois at Chicago (UIC), recipient of a 2007 New Investigator Research Grant
In her own words, investigator Dr. Orly Lazarov describes her research and what receiving Association funding has meant to her career.
The benefits of physical and mental fitness for prevention of age-related illnesses are unequivocal, and it is reasonable to assume that it would have comparable advantages for prevention of age-related neurodegeneration such as in Alzheimer's disease. While strategies for physical and mental fitness are common in hopes of preventing Alzheimer's, the mechanism underlying these strategies is poorly understood. Moreover, how do we ascertain the most effective tactics for preventing Alzheimer's disease?
Impact of Association funding
"Our research suggests that physical and mental stimulation can rescue critical aspects of brain function that are impaired in Alzheimer's disease and that methods that encourage brain plasticity may help prevent or treat Alzheimer's disease. … The Alzheimer's Association New Investigator Research Grant enabled us to successfully conduct this study and observe these exciting findings."
Environment and brain plasticity in animal models
Animal models can be very useful for identifying key variables by which one's environment and experience may affect the development and progression of disease. In our study, we proposed to let mice with the familial Alzheimer's disease (FAD)-linked mutant gene APPswe/PS1∆E9 experience a complex environment and examine its effect on the development of Alzheimer's-like changes in the brain and on critical aspects of brain plasticity (the brain's ability to change in response to a stimulus, such as learning). These aspects were the development of new neurons in the hippocampus, the seat of memory and learning in the brain, and long-term improvement in the communication between neurons in the brain, called long-term potentiation (LTP).
We showed that experience in a complex environment rescued mice's ability to generate new neurons in the hippocampus. This was accompanied by significantly reduced levels of hyperphosphorylated tau protein and the oligomeric forms of beta-amyloid, precursors of Alzheimer's disease, in the hippocampus and cortex of mice. In collaboration with Drs. Gustavo Pigino and Scott Brady at UIC, we observed that experience in a complex environment was linked to enhanced expression of neuronal anterograde motor kinesin-1, a protein that facilitates the transport of nutrients and subunits of the cell from the cell body to the synaptic terminals, the ends of axons where chemical messengers are released from one neuron, cross the synapse, and are taken up by the receiving neuron. In collaboration with Dr. John Larson at UIC, we found that environmental experience significantly enhanced LTP in the hippocampus.
Moving research forward
Our research suggests that physical and mental stimulation can rescue critical aspects of brain function that are impaired in Alzheimer's disease and that methods that encourage brain plasticity may help prevent or treat Alzheimer's disease. The Alzheimer's Association was instrumental in its support and contribution to this study.
The Alzheimer's Association New Investigator Research Grant enabled us to successfully conduct this study and observe these exciting findings.
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