Multimodal Gamma Stimulation Improves Activity but not Memory in Aged Tgf344-AD Rats

Abstract

Background: Multimodal sensory gamma stimulation is a treatment approach for Alzheimer’s disease that has been shown to improve pathology and memory in transgenic mouse models of Alzheimer's. Because rats are closer to humans in evolution, we tested the hypothesis that the transgenic rat line bearing human APP and PS1, line TgF344-AD, would be a good supplemental candidate to test the efficacy of this treatment. Current therapy approaches under investigation seek to utilize the immune response to minimize or degrade the accumulation of β-amyloid plaque load in mouse models designed to overexpress Aβ. However, many of these models lack some of the hallmarks of Alzheimer's disease, such as hyperphosphorylated tau and neuronal cell loss. The TgF344-AD transgenic rat model is a good candidate to bridge the gap between mouse models and clinical efficacy in humans. Objective: The objective of this study was to use multimodal gamma stimulation at light and auditory modalities simultaneously to test whether this enhances memory performance as measured by the object location task and the spontaneous alternation task Methods: In our study, we designed and built a low-cost, easy-to-construct multimodal light and sound gamma stimulator. Our gamma stimulation device was built using an Arduino microcontroller, which drives lights and a speaker at the gamma frequency. We have included in this paper our device’s parts, hardware design, and software architecture for easy reproducibility. We then performed an experiment to test the effect of multimodal gamma stimulation on the cognitive performance of fourteen-month-old TgF344-AD rats. Rats were randomly assigned to either an experimental group that received gamma stimulation or a control group that did not. Performance in a Novel Object Location (NOL) task and spontaneous alternation task was evaluated in both groups before and after the treatment. Results: Multimodal gamma stimulation did not improve memory compared to unstimulated TgF344-AD rats. However, the gamma-stimulated rats did spend significantly more time exploring objects in the novel location task than the unstimulated rats. In the spontaneous alternation task, gamma-stimulated rats exhibited significantly greater exploratory activity than unstimulated controls. Conclusion: Multimodal gamma stimulation did not enhance memory performance in the object location task or the spontaneous alternation task. However, in both tasks, the treatment group had improved measures of exploratory activity relative to the untreated group. We conclude that several limitations could have contributed to this mixed effect, including aging complications, different animal models, or light cycle effects.