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Neural Engineering

Neural Engineering - Poster Session D

Poster Z17 - Behavioral Effects of Osteopathic Cranial Manipulative Medicine on Transgenic Rat Model of Alzheimer’s Disease

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Alzheimer’s Disease is a neurological disorder that was the 7th leading cause of death in 2020 and 2021. Current findings have shown that the build-up of amyloid plaque impairs the glymphatic system resulting in improper fluid circulation in the brain. These factors can lead to the development of neuroinflammation and neuronal death, which can negatively alter the behavior and memory of those diagnosed. Research into Osteopathic Cranial Manipulative Medicine (OCMM/COM), a minimally invasive non-pharmaceutical mechanical therapy, as a treatment to fix improper fluid circulation has shown promising results. Previously we have found that COM reduced AB levels and improved excitatory neurotransmission in an aged rat AD model. Recent findings found significant differences in spatial learning behaviors between male and female wild type AD rat models post COM treatment. In addition, researchers have found that interstitial fluid flow was improved in a traumatic brain injury (TBI) pre-clinical model. To continue research efforts to understand the mechanisms and effects of COM, to the current study investigated the therapy’s effect on learning and memory in transgenic rat AD models using Morris Water Maze (MWM), Novel Object Recognition (NOR), and Open Field Test (OFT). Outcomes from the experiments will provide insight on how COM can be used to influence behavior in preclinical models of AD-like brains.

Materials and

Methods:  Male (M) and female (F) 18-month-old TgF344 rats were blindly placed into two treatment groups also separated by sex, COM males (COM-M), COM females (COM-F), Untreated Males (UT-M), Untreated females (UT-F). FingerTPS, nanosensor gloves, were worn by an Osteopathic Physician to quantify the pressure applied to the rat’s occipital squama during 7 days of treatment. The MWM assay was conducted over the course of 8 days using a tub that was divided into four quadrants. A platform was placed in the northwest zone and all rats began their 1st 60-second trial in the southwest zone. Days 1-4 were learning days, 5-7 were testing days, and day-8 was a platform-less day. Learning days involved 4 trials per rat, in clear water, with each trial happening in one of the quadrants. Testing days only required one trial, but the water was made opaque, and the water level was raised to match the height of the platform. Lastly, one trial was performed on day-8 along with the platform being removed. OFT trials were performed on day-7 of the timeline. Rats were placed in a box for 3 minutes to roam.

Results, Conclusions, and Discussions: Average pressure and duration of COM were 2.596N±1.452 and 249.08s±3.118, respectively. MWM results revealed significant differences across the learning days within group performance. All treatment groups saw a significant decrease with the largest from the COM-F(55.5±7.148 v. 18.5±10.09, p=.002) and the UT-M (57.33±6.532v.13±1043, p<.001). No significant difference was found for the testing days. Holistically, the learning and testing days show a decreasing trend in escape latency for all groups. Parameter, distance moved, also showed significance for COM comparing day 5 to 6 (p=.020) and 5 to 7 (p=.010). Results from OFT show COM-M having a significantly higher number of visits for inner zone (p <.001) and outer zone (p=.001) visits when compared to COM-F. However, the duration for the same comparison was not significant. There was also no significance between the treatment groups for duration and frequency of grooming and rearing. This also applies when groups are
separated by sex.

Results from the experiments have shown that COM influences behaviors associated with spatial learning and anxiety-like behavior. MWM results show a trending decrease in latency and distance moved indicating an increase in learning within the COM group. The lack of significance when separated by sex for the treatment groups also suggests that COM does not significantly hinder behaviors associated with memory in MWM. For OFT, COM-M rats frequently swapped zone location more than their female counterparts even though duration, grooming, and rearing parameters were not significant. This suggests COM-M were more explorative or restless.

Based on current results, COM shows potential as a novel treatment for neurological diseases. The lack of significance in escape latency and the decreasing trends found that COM may have individualized effects. Unlike pharmaceuticals, COM is specifically used for
individualized treatment since patients may have different cranial rhythmic impulses. For this study, the cohort may mask individual improvements. Results have also shown that COM had no adverse effects due to minimal significant differences between treatment groups. To fully understand the significance of the treatment, we plan to investigate glucose uptake and protein changes in COM and UT rats to investigate differences on the molecular level as well.

Acknowledgements (Optional):