Robo4 Project

Presenter(s): Byron Lee—Human Physiology

Faculty Mentor(s): Ashley Walker

Session 6: Interact & React

Aging is associated with the impairment of the neurovascular unit, and this potentially leads to increased Alzheimer’s disease pathology and cognitive impairment . A specific axon guidance receptor, Robo4, is important in maintaining the structure and restrictive barrier of the blood-brain barrier (BBB) . We predicted that the knockout of Robo4, and the subsequent increase in BBB permeability, will result in cognitive dysfunction . Therefore, Robo4 signaling pathways may potentially be a valuable target for therapeutic treatments of AD . In the present study, we studied Robo4 knockout (Robo4 -/-) and wild type (Robo4 +/+) mice crossed with mice containing mutations in amyloid precursor protein (APP), leading to greater aberrant amyloid-beta production . To examine the effect of aging, we studied young and old wildtype C57BL6 mice . We assessed cognitive function by conducting Nest Building tests and Morris Water Maze . We found that old C57BL6 mice had impaired cognitive function compared to young C57BL6 mice . However, when Robo4 x APP groups were compared, we found no differences in cognitive function . These preliminary results suggest that aging has a stronger effect on cognitive function than Robo4 knockout . Additional studies are needed to determine the effect of Robo4 knockout on blood-brain barrier permeability and amyloid-beta accumulation .

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