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Investigating the role of glymphatic clearance of amyloid beta through exercise in C57BL6/J mice
Jordan, Rachel
Jordan, Rachel
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2019
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2019-05-19
Abstract
Alzheimer's disease (AD) is a very prevalent neurodegenerative disorder characterized by widely distributed amyloid plaques and neurofibrillary tangles. AD is clinically associated with a progressive decline in memory and other cognitive functions. Several pieces of evidence have indicated that amyloid beta accumulates to form oligomeric states in the AD brain and cause the cognitive dysfunction commonly seen in patients. While a decrease in cognitive function is considered a hallmark of the disease, AD patients also exhibit decreased motor abilities and difficulties learning new motor tasks. Our lab's previous investigations found voluntary running to decreased amyloid beta burden in C57/BL6 mice. The present experiment seeks to further explore the mechanism through which exercise induced amyloid beta clearance occurs. Previous studies have pointed to the function of the glymphatic system in the clearance of amyloid beta. The level and distribution of aquaporin 4 (AQP4) is crucial to the normal function of the glymphatic system. We hypothesize that mice receiving intraperitoneal TGN injections, a selective AQP4 antagonist, thus blocking the function of AQP4, will experience decreased glymphatic clearance of amyloid beta. To test this hypothesis mice were given intraperitoneal injections of saline every morning for one week. The following two weeks, doses of either TGN or saline injections were given twice daily morning and night. During this period, mice were moved into individual cages with running wheels at 6:00 PM daily and returned to group housing cages the following morning at 7:00 AM. 24 hours following treatment mice were trained and tested in hippocampus dependent contextual fear conditioning (CFC) to explore possible cognitive differences between treatment groups.
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Biology