Alteration of neural network and hippocampal slice activation through exosomes derived from 5XFAD nasal lavage fluid

Abstract

Exosomes contain various intracellular biomarkers reflecting the condition of cells, organs, and subjects. Under neurodegenerative conditions, they contrive in detrimental neuronal communications leading to the initiation and propagation of neurodegenerative symptoms. Since the exosomes in olfactory fluid are readily accessible to collect in ample amount noninvasively and highly enriched in neural biomarkers, they can be a primary biomarker if we can verify precise pathophysiological information from them. Here we show that exosomes from nasal lavage fluid (NLF) of the neurodegeneration model animal, 5XFAD mice, induce the pathological network activity in neuronal cultures. We separated intact NLF exosomes from the 5XFAD and wild-type mice via a high-efficacy microfluidic system and applied them to the primary cortical neurons and organotypic hippocampal slice cultures (OHSC), whose neuronal activities were monitored by a high-density microelectrode array system. We found that NLF exosomes from 5XFAD mice increased the firing rate of neuronal spikes with augmentation of neuronal connectivity similar to the effect of pathological amyloid beta oligomer treatment. Furthermore, the current source densities, computed from the local field potentials, were elevated in OHSCs incubated with the exosomes, suggesting a pathological shift in synaptic and membrane currents. Those results demonstrate that NLF exosomes from neurodegeneration model can effectively modify neuronal networks and suggest that this property can serve as a functional biomarker for Alzheimers disease.