Female TgF344‐AD hippocampal plasticity after estrogen deprivation

Abstract

AbstractBackgroundAlzheimer’s Disease (AD) is the seventh leading cause of death worldwide, disproportionately affecting women, with two‐thirds of individuals with AD being female. A decrease in circulating ovarian estrogen during menopause is believed to be a contributing factor to this discrepancy in disease prevalence. AD pathology is known to impact synaptic transmission in the hippocampus, resulting in memory deficits, a hallmark symptom of AD. This study investigates the effect of estrogen deprivation in the dentate gyrus (DG) and CA1 region, areas affected early on in the disease and crucial for memory. As the disease progresses, deficits are seen in the dentate gyrus prior to CA1 region supporting the anatomical spread of the pathology.MethodSynaptic signaling was assessed in DG and CA1 hippocampal subregions of 9 month old TgF344‐AD female rats who underwent long‐term (from ages 3 to 9 months) ovarian hormone deprivation. Extracellular dendritic field potential recordings were conducted in the DG by stimulating the medial perforant path onto dentate granule cells, and in the CA1 region by stimulating Schaffer collateral axons. Input/output relationship, paired pulse ratio, and long term potentiation were assessed, analyzed, and statistically compared between TgF344‐AD rats and non‐transgenic hormone deprived littermates.ResultIt was found that AD females were able to maintain synaptic transmission as there were no significant differences found in the input/output relationship, paired pulse ratio, or long term potentiation between AD animals and their controls.ConclusionThese results show that at this early stage in the disease, ovarian estrogen deprivation does not accelerate synaptic impairment. These results also suggest the possibility that a compensatory mechanism exists at these synapses to maintain function.