VCOM Research Day Program Book 2023

Medical Student Research Biomedical

Hope Tobey; Lina Kwapisz; Alyssa Ingram; Patrick Duggan; Maya Pillai; Seth Boehringer; De’ Yana Hines; Joseph Piwowarski; Anshul Ramanathan; Ramu Anandakrishnan; Pamela VandeVord; Blaise Costa Corresponding author: 16 A Nanosensor-Monitored, Quantified Cranial Osteopathic Manipulation Alters Alzheimer’s Disease Phenotype in Transgenic Rats Expressing Mutant Amyloid and Presenilin Proteins

Edward Via College of Osteopathic Medicine-Virginia Campus

Cranial Osteopathic manipulation (COM) is clinically used for the treatment of various refractory disease conditions including attention deficit hyperactivity disorder and autism spectrum disorders. With the goal of understanding the molecular mechanisms of COM treatment, and to promote COM as an adjunct therapy for Alzheimer’s disease (AD), we have evaluated COM effect on transgenic rat model of AD. Digitally quantified COM treatment was performed once every day for seven days with nanosensor gloves that recorded the force applied to the skull. Morris water maze (MWM) spatial learning and memory assay and novel object recognition assay (NORA) were performed to access COM-induced changes in AD animals. Results obtained from MWM experiments reveal that several parameters related to cognitive function were significantly altered in the COM group compared to the untreated (UT) control group animals on day-5 of the MWM experiment. These parameters include (1) average speed, (2) time moving towards

NW zone, (3) signed initial heading error to the NW zone, (4) shortest visit to the NW zone, (5) signed initial heading error to the platform zone, (6) maximum distance to the platform zone border, and (7) average distance from the platform zone border. In NORA assay, COM treated animals spent numerically more time (COM, 31.4±13.7 vs 26.6±16.51s; UT, 15.5±3.25 vs 24.0 ±12.0s) exploring the novel object. MWM and NORA assay these findings, together, indicate that COM treatment could improve cognitive function in AD rats. Furthermore, rat brain hippocampal tissue proteome analysis identified that COM significantly increases the expression of serine threonine kinase P21-activated kinase 3 (PAK3), in addition to fifty other proteins that are different between COM and UT groups. A transcriptome study on the second half of the hippocampal tissue is underway to compare with the proteome assay findings. Western blots on hippocampal tissue lysate reveal a significant increase in AQP4 expression

in COM-treated animals compared to UT. Further, ELISA assays show that COM significantly reduced pCREB levels in the cerebellar region. These findings corroborate our previous reports of COM on naturally aged rat model of AD. Overall, based on the outcome of our ongoing studies clinicians are able to promote COM as an evidence based, low cost, less invasive, adjunct treatment strategy for Alzheimer’s disease.


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