Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats

BackgroundSoluble amyloid-beta oligomers (A beta o) begin to accumulate in the human brain one to two decades before a clinical diagnosis of Alzheimer's disease (AD). The literature supports that soluble A beta o are implicated in synapse and neuronal losses in the brain regions such as the hippocampus. This region importantly contributes to explicit memory, the first type of memory affected in AD. During AD preclinical and prodromal stages, people are also experiencing wake/sleep alterations such as insomnia (e.g., difficulty initiating sleep, decreased sleep duration), excessive daytime sleepiness, and sleep schedule modifications. In addition, changes in electroencephalographic (EEG) activity during wake and sleep have been reported in AD patients and animal models. However, the specific contribution of A beta o to wake/sleep alterations is poorly understood and was investigated in the present study.MethodsChronic hippocampal injections of soluble A beta o were conducted in male rats and combined with EEG recording to determine the progressive impact of A beta pathology specifically on wake/sleep architecture and EEG activity. Bilateral injections were conducted for 6 consecutive days, and EEG acquisition was done before, during, and after A beta o injections. Immunohistochemistry was used to assess neuron numbers in the hippocampal dentate gyrus (DG).ResultsA beta o injections did not affect the time spent in wakefulness, slow wave sleep (SWS), and paradoxical sleep but altered EEG activity during wake and SWS. More precisely, A beta o increased slow-wave activity (SWA; 0.5-5 Hz) and low-beta activity (16-20 Hz) during wake and decreased theta (5-9 Hz) and alpha (9-12 Hz) activities during SWS. Moreover, the theta activity/SWA ratio during wake and SWS was decreased by A beta o. These effects were significant only after 6 days of A beta o injections and were found with alterations in neuron counts in the DG.ConclusionsWe found multiple modifications of the wake and SWS EEG following A beta o delivery to the hippocampus. These findings expose a specific EEG signature of A beta pathology and can serve the development of non-invasive and cost-effective markers for the early diagnosis of AD or other amyloid-related diseases.