Fellowship for Pleiss: Astrocytic Calcineurin and Connexin43 Gap Junctions in Alzheimer's Disease

Grants and Contracts Details

Description

As the sixth leading cause of death that affects over 5.2 million people, Alzheimer’s disease (AD) is becoming a health crisis. To much disappointment, previous clinical trials have shown little success in finding a treatment for this devastating disease. Thus, it is critical that new and alternative molecular targets be explored. The proposed project will test the overarching hypothesis that calcineurin (CN) and connexin43 (Cx43) interactions disrupt gap junction (GJ) coupling in astrocytes during the progression of AD leading to detrimental changes in neurologic function. This project will use a multi-disciplinary approach to investigate the hypothesis using an array of AD model systems, including human hippocampal specimens, APP/PS1 transgenic mice, and rat primary astrocyte cultures. In addition to the excellent model systems, this project will use a variety of cutting-edge techniques, including fluorescence resonance energy transfer (FRET), adeno-associated virus (AAV) - mediated gene delivery, and slice electrophysiology. The overarching hypothesis will be examined through three independent specific aims which are as follows: to test the hypothesis that CN interacts with Cx43 during the progression of AD using techniques such as FRET and co-immunoprecipitations (Co-IPs); to test the hypothesis that beta amyloid (Aâ) disrupts gap junction (GJ) coupling in a CN-dependent manner using techniques such as dye coupling and Western blot; to test the hypothesis that CN/Cx43 interactions disrupt GJ coupling and neurologic function in a mouse model of AD using cognitive measures such as the active avoidance paradigm and techniques such as dye coupling, Western blot, and slice electrophysiology. This project not only provides superior training in neuroscience research, but also will provide extremely valuable information into a potential new therapeutic target for AD.
StatusFinished
Effective start/end date2/1/151/31/16

Funding

  • National Institute on Aging: $29,736.00

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