The mice had unusually low levels of estrogen because their ovaries were removed at an early age. However, scientists were still able to rescue learning ability by delivering the correct gene to produce estrogen receptor-alpha directly to the hippocampus.
Mice that lacked the estrogen receptor showed poor ability to locate a platform hidden in a small swimming tank over a training period of several days. After receiving the gene, the mice learned to locate the platform in two days of training.
"This research shows that when the estrogen receptor-alpha is restored to adult mice that have been missing it their entire lives, it is still possible to enhance memory and learning," said John H. Morrison, Ph.D., dean of basic sciences and the Graduate School of Biological Sciences at Mount Sinai School of Medicine, who did not participate in the research. "This is good news for moving forward to develop clinical interventions and therapeutics because it appears critical damage was not done to brain circuitry during early development. There has also been debate about which of at least two estrogen receptors is key to synaptic health. Clearly estrogen receptor-alpha plays a critically important role in hippocampal organization and function."
Recordings made from the brain tissue of treated mice showed signals were strongly communicated across the gaps, or synapses, between hippocampal cells, similar to what would happen with estrogen replacement.
"Investigating the impact of genetically replacing the estrogen receptor at the cellular, synaptic and behavioral levels is a scientific tour de force which provides a strong
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University of Florida