Estrogens, Memory and the Brain - A New Animal Model

Schlinger, Barnett

Abstract

Estrogens are critical for optimal growth and then function of the brain. Indeed, age-induced estrogen loss may underlie some deficits in memory function and may contribute to the symptoms of neurodegenerative diseases such as Alzheimer s. While our knowledge of the effects of estrogens on brain regions associated with cognitive function are expanding, the linkage between estrogen's actions on brain and memory function remain incomplete. Using a songbird animal model, we have initiated experiments to test the idea that estrogens influence hippocampal (HF) structure and memory function. Our early results are exciting and indicate that inhibition of the estrogen synthetic enzyme aromatase in the zebra finch impairs performance on a spatial memory task and significantly reduces the volume of the HF and the number and intensity of HF neurons expressing the calcium-binding protein calbindin D28K. This study stemmed from earlier research showing that a) songbirds have exceptional memory capabilities; b) they show substantive plasticity of neural circuits, including those in HF; c) and memory functions can change seasonally, presumably because a changing hormonal environment promotes the neural changes associated with increased and decreased memory function. We discovered that songbirds express aromatase in very high amounts in HF, suggested that the hormonal substrate underlying changes in songbird memory function may indeed be estrogen. This current line of research investigating estrogen effects on behavior of HF structure in these birds involves collaboration between an avian neuroendocrinologist (Schlinger) and a behavioral neurobiologist (Clayton). Although our early data are exciting, we need to perform additional critical experiments to confirm the estrogen- dependence of these findings. We propose studies here to allow for continued growth of this collaboration in tacking this potentially unique system to understand more about the role of estrogens in cognitive function and the effect of a changing estrogen environment on hippocampal structure and function.