The Effects of Intrahippocampal Estradiol Administration on Spatial Memory and Protein Expression in Rats Fed a High Fat Diet

Estradiol acts throughout the body; one key target that expresses large numbers of estradiol receptors is the brain, and specifically the hippocampus. Estradiol can exhibit neuroprotective effects in the brain. However, the set of pathways through which this occurs is not well understood. In vitro work has shown that administration of estradiol to hippocampal neurons inactivates caspase 3, a protease involved in apoptosis and the cleavage of tau. Cleavage of tau results in the formation of neurofibrillary tangles. Together with formation of amyloid-beta plaques, this is one of the hallmarks of Alzheimer’s disease. We tested the hypothesis that administration of estradiol to rats might attenuate the cognitive impairment caused by the ingestion of a high fat, diabetogenic diet whose long-term consumption causes insulin resistance and Alzheimer’s disease pathologies. Administration of estradiol unexpectedly did not ameliorate the impairment seen on a spatial working memory task or a novel object recognition task. In addition to behavioral measures, post-mortem analyses of hippocampal tissue measured molecular markers associated with estradiol signaling and memory formation. Ultimately, this study aims to elucidate mechanisms involved in a possible neuroprotective role for estradiol in individuals prone to cognitive dysfunction brought about by metabolic disease.