Poster Session 06 Program Schedule
02/15/2024
04:00 pm - 05:15 pm
Room: Shubert Complex (Posters 1-60)
Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2
Final Abstract #4
Poster Symposium: Current Directions in Women's Neuropsychology Research — Abstract 3
In vivo calcium imaging reveals sex differences in ventral hippocampal activity in Alzheimer’s disease mice
Kameron Kaplan, Rosalind Franklin University of Medicine and Science, North Chicago, United States
Naina Beishembieva, Rosalind Franklin University of Medicine and Science, North Chicago, United States
Lainey Toennies, Rosalind Franklin University of Medicine and Science, North Chicago, United States
Holly Hunsberger, Rosalind Franklin University of Medicine and Science, North Chicago, United States
Category: Dementia (Alzheimer's Disease)
Keyword 1: dementia - Alzheimer's disease
Keyword 2: anxiety
Objective:
Neuropsychiatric symptoms (NPS), such as depression and anxiety, are observed in 90% of Alzheimer’s disease (AD) patients, two-thirds of whom are women. NPS usually manifest long before AD onset creating a therapeutic opportunity. Our laboratory examines the impact of anxiety on AD progression and the underlying brain-wide neuronal mechanisms. We’ve shown that anxiety is strong predictor of dementia transition using the Alzheimer’s disease neuroimaging initiative (ADNI) dataset and that female subjects positive for anxiety and amyloid transitioned more quickly to dementia than male subjects. In rodents, we’ve confirmed anxiety-like behavior and cognitive decline occur earlier in female mice and brain-wide analysis revealed changes in regional correlations and overall network connectivity in AD mice. From these data we aim to understand the dynamic changes occurring across ages and to better understand the neural circuitry controlling this anxiety-like behavior.
Participants and Methods:
We obtained a snapshot of brain activity in previous studies. How neural activity changes throughout AD progression in male and female mice and throughout different memory and anxiety tasks is unclear. Because the vCA1 is implicated in anxiety-like behavior and greater activation resulted in decreased memory, we will target the vCA1. Male and female 2-month-old APP/PS1 (AD) and 129S6 control mice will be injected with pGP-AAV1-syn-jGCaMP8f-WPRE virus and implanted with a GRIN lens into the vCA1. Mice will recover for four weeks. All mice will be administered an elevated plus maze (EPM) protocol (anxiety) and contextual fear conditioning (CFC) protocol (memory). Using the nVoke miniature microscopes, we will image neural activity in freely moving mice while they encode and retrieve individual experiences. Calcium transients, behavior-specific cells, and how cell firing changes with age will be measured.
Results:
Using our activity dependent-tagging mouse line which allows us to tag cells active during encoding and retrieval of an experience, we’ve discovered that female AD mice exhibit a decrease in overall network activity at 6 months while male AD mice show an increase indicating a difference in disease progression. Therefore, we hypothesize that female AD mice will exhibit increased calcium transient activity at 2-4 months of age compared to males, but that males will experience this increase at 6-8 months of age. At 6 months of age AD female mice will begin to exhibit a decrease in calcium transient activity due to loss of neurons.
Conclusions:
While future studies are needed to understand whether anxiety is a predictor, a neuropsychiatric biomarker, or a comorbid symptom that occurs during disease onset, these results suggest that AD network dysfunction is sexually dimorphic, and that personalized medicine may benefit male and female AD patients rather than a one size fits all approach.
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