Ongoing Electroencephalographic Rhythms Related to Exploratory Movements in Transgenic TASTPM Mice

Background: The European PharmaCog study (http://www.pharmacog.org) has reported a reduction in delta (1-6Hz) electroencephalographic (EEG) power (density) during cage exploration (active condition) compared with quiet wakefulness (passive condition) in PDAPP mice (hAPP Indiana V717F mutation) modeling Alzheimer's disease (AD) amyloidosis and cognitive deficits. Objective: Here, we tested the reproducibility of that evidence in TASTPM mice (double mutation in APP KM670/671NL and PSEN1 M146V), which develop brain amyloidosis and cognitive deficits over aging. The reliability of that evidence was examined in four research centers of the PharmaCog study. Methods: Ongoing EEG rhythms were recorded from a frontoparietal bipolar channel in 29 TASTPM and 58 matched 'wild type' C57 mice (range of age: 12-24 months). Normalized EEG power was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during the passive and active conditions. Results: Compared with the 'wild type' group, the TASTPM group showed a significantly lower reduction in IDF power during the active over the passive condition (p<0.05). This effect was observed in 3 out of 4 EEG recording units. Conclusion: TASTPM mice were characterized by 'poor reactivity' of delta EEG rhythms during the cage exploration in line with previous evidence in PDAPP mice. The reliability of that result across the centers was moderate, thus unveiling pros and cons of multicenter preclinical EEG trials in TASTPM mice useful for planning future studies.