0301 Does Orexin Influence Sleep Fragmented Brain Inflammation? A Pilot Study

Introduction Fragmented sleep occurs when there are repetitive, short interruptions of sleep, resulting in less than six hours of sleep per day. Overall, however, in the United States, sleep fragmentation is reported by 30% of employed adults. Sleep fragmentation may be a risk factor for Alzheimer's disease, and orexin reduction appears effective in reducing amyloid plaque formation in mice with transgenic Alzheimer's disease. Orexin is a neuropeptide that regulates arousal, wakefulness, and appetite. Thus we hypothesized that loss of orexin might also be protective against sleep disruption injury in non-Alzheimer's mice. This study aims to combine sleep fragmentation with orexin loss to see if brain health is severely reduced. Methods The 24 mice in this study were split into four groups: B6 rested, B6 sleep fragmented, orexin knockout rested, orexin knockout sleep fragmented. The sleep fragmented mice were placed on a shaker table for 10½ weeks to initiate chronic sleep loss. The mice were all perfused within five to eight months of birth, and then the brains were cryopreserved and sliced. These sections were immunolabeled with different protein antibodies using immunohistochemistry techniques. The stained brains were either analyzed through microscope stereology counts or computer image analysis. Results Two-way ANOVA analysis for tyrosine hydroxylase, ionized calcium binding adaptor, and vesicular acetylcholine transporter had p Conclusion Our results show that knocking out orexinergic neurons causes hippocampal tissue damage, dampens the functioning of synapses, and diminishes the ability of the brain to adapt through plasticity and memory. Sleep fragmentation, however, increases phagocytic activity, and harms the acetylcholine and norepinepherine neurotransmitter pathways. When combined, cell communication worsens and the blood brain barrier loses function, resemblant of neurodegenerative diseases. Support (If Any) NIH AG054104; AG064231