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2008 Grants - Marie
Does NGF Deprivation Lead to Glutamatergic/GABAergic Network Imbalance?
Helene Marie, Ph.D.
European Brain Research Institute
2008 New Investigator Research Grant
Cholinergic neurons are brain cells that participate in many learning and memory functions. They communicate with one another using receptors, or "docking sites," for chemical messengers. Previous research has shown that one of these docking sites, called alpha7 nicotinic acetylcholine receptor (alpha7 nAChR), has been linked to Alzheimer's disease. In people with Alzheimer's, the activities of alpha7 nAChR become inhibited. Damage to this receptor can lead to the overproduction of chemical messengers called glutamates. Such overproduction, in turn, may impair cell-to-cell communication in the brain and induce the cognitive decline characteristic of Alzheimer's.
Other research has found that reduced alpha7 nAChR activities—and the resulting cognitive decline—are caused by the inhibition of a protein called nerve growth factor. Nerve growth factor is a vital molecule in the production and maintenance of cholinergic neurons.
Helene Marie, Ph.D., and colleagues propose to test whether the lack of nerve growth factor leads to 1) the inhibition of alpha7 nAChR, 2) the overproduction of glutamate and 3) cognitive decline and other Alzheimer-related pathologies. For this effort, they will use mice genetically engineered to develop Alzheimer-like symptoms and to lack sufficient nerve growth factor. Dr. Marie's team will also assess whether artificially promoting alpha7 nAChR activity in the animals can alleviate Alzheimer symptoms.
The outcomes of this study could shed new light on the biological mechanisms underlying Alzheimer's disease. Such knowledge could lead to novel therapies for the disease.