This is because there is a significant discordance between basic and clinical science. The Hunsberger Alzheimer’s & Aging Laboratory aims to address this translational gap by using transgenic AD rodent models and large human datasets. More specifically we are interested in unraveling sex differences throughout aging and AD with an emphasis on mood disorders. I grew interested in sex differences upon realizing that most AD studies were performed using male rodents even though 2/3rds of AD patients are women. Additionally, 90% of patients with AD also suffer from anxiety or depression. Our long-term goal is to discover early-stage biomarkers and develop personalized therapeutics for men and women suffering from AD.
“The major difference between rats and people is that rats learn from experience.” ~ B.F. Skinner
Behavior is fundamental to the Hunsberger Lab. We use a variety of tests to measure avoidance or anxiety behavior, depression, and memory.
Tests: Open Field, Elevated plus maze, light dark box, novelty suppressed feeding, marble burying assay, Barnes maze, novel object task, contextual fear conditioning, Piezo sleep chambers
The Piezo sleep system allows us to monitor sleep and wakefulness in mice without invasive procedures.
To determine the impact of the estrus cycle on aging and AD, we use an impedance tracker and vaginal cytology to track rodent menstrual cycles.
Using the inscopix nVoke miniscopes we can manipulate and visualize cells firing in real time during a behavior or experience. This allows for a dynamic view of the brain which complements our snapshot immunohistochemistry technique.
A snapshot of the brain during an experience. Immunohistochemistry allows us to use antibodies with fluorescent markers to tag cells of interest throughout the brain.
The Echo scope is a novel automated fluorescent microscope that can perform live cell imaging, multi-channel imaging, stitching, z-stacking, auto-focus, and hyperscan. Your eyepiece is a Microsoft surface computer with touch screen capability.
The ArcCreER T2 mice are used to permanently tag activated neurons after an experience (Denny et al., 2014; Root et al., 2014). To achieve both temporal control and flexibility in transgene expression, a CreER T2 system was placed under the control of the Arc gene promoter. in vitro studies have established a requirement for Arc in long-term memory of hippocampus-dependent tasks. This line is unique in that, unlike previous semi-permanent tools, it allows for the permanent tagging of previously active neural ensembles. The ArcCreER T2 mice are bred to an enhanced yellow fluorescent protein (EYFP) line, allowing for indelible EYFP labeling of Arc + cells after administration of 4-hydroxytamoxifen (4-OHT). Therefore, cells that express Arc + after an experience will be tagged in green, thus allowing for a comparison between cells that are activated during one experience with those that are activated during a second experience. By crossing the ArcCreER T2 x EYFP mice with the APP/PS1 AD line, we can measure changes in neural circuitry between males and females, across ages, and throughout AD progression.