Cognitive dysfunctions and spontaneous EEG alterations induced by hippocampal amyloid pathology in rats

We aimed to determine the effects of different doses of amyloid-beta (Aβ) peptide on learning and memory, and whether the changes in brain oscillations induced by dose-dependent accumulation of Aβ could be used as biomarkers to detect early stages of Alzheimer's disease (AD).

Male albino Wistar rats aged 3 months were randomly divided into four groups (n ​= ​12/group) obtained by i. h. Injection (to the dorsal hippocampus) of saline or different doses of 0.01 ​μg/μl, 0.1 ​μg/μl, and 1 ​μg/μl of Aβ. After two weeks of recovery period, open field and novel object recognition tests were performed and spontaneous EEG recordings were obtained. Later, hippocampus tissues were collected for Western blot and ELISA analysis.

A significant decrement in recognition memory was observed in 0.1 ​μg/μl, and 1 ​μg/μl injected groups. In addition, Aβ accumulation induced significant decrement of the expression of NeuN, SNAP-25, SYP, and PSD-95 proteins, and led to the increment of GFAP expression in hippocampus. Moreover, we detected remarkable alterations in spontaneous brain activity. The hippocampal Aβ levels were negatively correlated with hippocampal gamma power and positively correlated with hippocampal theta power. Also, we observed significant changes in coherence values, indicating the functional connectivity between different brain regions, after the accumulation of Aβ. Especially, there was a significant correlation between changes in frontohippocampal theta coherence and in frontotemporal theta coherence.

Our findings indicate that Aβ peptide induces AD-like molecular changes at certain doses, and these changes could be detected by evaluating brain oscillations.