Excitability and glymphatic function in an animal model of Alzheimer’s disease

Background APPswe/PS1dE9 mice reproduce features of amyloid β (Aβ) pathology and neuronal dysfunction as reflected in electrophysiological recordings hyperexcitability. This leads to changes sleep-wake-rhythm, downstream affecting brain clearance functionality. Our objective is investigate the effect circadian rhythm Aβ on efficacy mice. Method First, we examined wide distribution an intrahippocampal injected fluorescent dye. Dye was at 6 am (post wake period) or pm sleep sampled 1 3 h post injection for histological analysis (Figure 1A) n = transgenic non-transgenic per group. Secondly, vivo approach analyzed a gadolinium based contrast agent using T2-RARE sequence 7 Tesla small animal MRI scanner (Bruker BioSpin GmbH, Germany) 1B) 4 We measured values brightness manually defined regions interest with PMOD software (version 3.7; Technologies LLC, Switzerland). Result In first experiment, were able observe dye parenchyma surrogate interstitial net flux. Preliminary results point rhythm, trend better shortly after period observed. Furthermore, possible detrimental phenotype observed comparison they showed lesser independent day-time. With second approach, influx efflux applied into cerebrospinal fluid. data increased slope well decreased Conclusion Histological stereotactic feasible method investigation outlining daytime pathology. However, MR-imaging promising tool will be disease progression longitudinally. Further experiments needed ensure these preliminary maybe also underlying mechanistic basis.