Effects of synaptic dysfunction induced by amyloid beta peptide on cognitive functions and evaluation via brain oscillations

Objective: The aim of this thesis is to determine the effects of different doses of intrahippocampal (i.h.) injection of amyloid beta (Aβ) 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 synaptic dysfunctions in the early stages of the Alzheimer's disease (AD). Method: 3-month-old male Wistar rats were randomly divided into four groups (n=15 per each group) obtained by i.h. injection of saline or Aβ: Sham, Aβ1 (0.01 µg/µL), Aβ2 (0.1 µg/µL) and Aβ3 (1 µg/µL). After recovery, learning and memory tests were performed and spontaneous EEG recordings were obtained to determine changes in brain activity induced by Aβ accumulation. At the end of the experiment, the hippocampus tissues were collected for biochemical analysis. Results: The Aβ injection induced significant increases in hippocampus Aβ levels and a significant decrease in recognition memory was observed in Aβ2 and Aβ3 groups. In addition, we found that Aβ accumulation induced significant decrement of the number of mature neurons and expressions of pre- and post-synaptic proteins and learning-related proteins, and leads to the increment of the astrogliosis in the hippocampus. Moreover, remarkable alterations induced by Aβ was observed in spontaneous brain activity, and hippocampal Aβ levels were negatively correlated with hippocampal gamma power, while they were positively correlated with hippocampal theta power. Also, the Aβ accumulation has significant adverse effects on functional connectivity. Especially, after the injection of Aβ, there was a correlation between the changes in frontohippocampal theta coherence and in frontotemporal theta coherence. Conclusion: Our findings indicate that Aβ peptide induces AD-like molecular changes at certain doses, and these changes can be detected by evaluating brain oscillations. Key words: Amyloid beta, learning and memory, EEG, coherence, rat