Western-Style Diet Alters Neuronal Morphology in the Hippocampus and Entorhinal Cortex of Ovariectomized Female Rats With and Without Estradiol

Rates of obesity and dementia are rising around the world. Research suggests an association between diet-induced obesity and cognitive impairments; however, past studies have primarily examined male subjects. Due to estrogens’ effects on behavior and neuronal structure, it is crucial to explore the effect of obesogenic diets in the presence and absence of estrogens. This is of particular interest because high-fat, high-sugar diets have been shown to halt reproductive cycling and disrupt reproductive hormone levels. Additionally, all women will enter menopause, which has been associated with an increased risk of developing Alzheimer’s disease. While previous studies have utilized gonadally intact females, the present study compares the effect of a Western-style Diet (WSD) on memory task performance and neuronal morphology in female Sprague-Dawley rats (n = 38) with and without administration of a constant low-dose estradiol pellet. This more closely replicates the menopausal and perimenopausal states. All females were ovariectomized (OVX) and half were implanted with a slow-release 17 β-estradiol pellet (OVX+E). After ten weeks of diet exposure, spatial and episodic memory were assessed using the Morris Water Maze (MWM) and Novel-Object Recognition (NOR) tasks, respectively. Brains were removed at termination and tissue was stained using the Golgi-Cox method. Neurons in the hippocampus and entorhinal cortex (EC) were imaged and digitally reconstructed. Results demonstrated higher body adiposity and TNF-α levels in WSD-fed animals, and lower cholesterol levels in females with estradiol. WSD OVX+E females showed reduced dendritic arborization in a Sholl analysis of the entorhinal cortex, raising questions about estradiol’s neuroprotective actions. WSD OVX females demonstrated reduced dendritic complexity in the CA1 hippocampus, suggesting a neuroprotective role of estradiol in the hippocampus, but not in the entorhinal cortex, as well as differential susceptibility to diets. These results demonstrate the importance of further investigating the role of estrogens in obesity-related impairments. This work was supported by the SRS student research fund and the Lenfest endowment. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.