The Effect of Menopause and Metabolic Disease on Neurogenesis in an AD Mouse Model
Aaron Paul1, Charly Abi Ghanem3, Riane Richard1, Kristen Zuloaga2
1Albany Medical College, 2Department of Neuroscience and Experimental Therapeutics, Albany Medical College, 3Psychology, State University of New York at Binghamton
Objective:
We hypothesize that menopause and metabolic disease will disrupt adult hippocampal neurogenesis (AHN) in Alzheimer’s mice. AHN drops sharply during early stages of AD via mechanisms that still remain unknown.
Background:
Alzheimer’s Disease (AD) is an age-related neurodegenerative disorder. AD pathology can begin more than twenty years before symptoms appear, with factors such as genetics, sex, and age increasing the risk for disease. Nearly two-thirds of individuals with AD are women, most of whom are post-menopausal. Metabolic disease is also a known risk factor for AD.
Design/Methods:
Four groups of female AppNL-F knock-in mice were utilized to model AD. To induce menopause, i.p. injections of 4-vinylcyclohexene diepoxide were administered, with the control mice injected with sesame oil. To model metabolic disease, mice were put on a high fat (HF, 60% fat) or low fat (LF, control) diet. Mice were randomized in cohorts, with 4 groups created to account for all combinations of diet and menopause (n=5-8 mice/group). At 9 months, 40 days before the endpoint, mice were injected with 5-ethynl-2’-deoxyuridine (EdU) for three consecutive days. Coronal brain slices were then immunolabeled for EdU (newly born cells), DCX (doublecortin, immature neuroblasts), and NeuN (mature neurons) to determine changes in neurogenesis due to these factors.
Results:
Quantification of EdU+ cells, DCX+ cells and NeuN+ cells revealed that menopause impacts hippocampal neurogenesis in a diet dependent manner. Individually, menopause or HF diet decreased neural proliferation (p<0.05). Concurrently, menopause and HF diet increased the percentage of new neurons that may be arrested in an immature intermediate phase (p<0.05).
Conclusions:
Menopause and metabolic disease can accelerate AD-associated risk factors. This can be potentially through alteration in hippocampal neurogenesis, with HF diet and menopause independently contributing to decline in neural proliferation. The results highlight the importance of further examining the interplay between menopause and diet in the context of AD.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.