Modification of neural activity in the presence of exosome derived from nasal lavage fluid of neurodegenerative animals

Abstract

Exosome is tiny cellular vesicles with a diameter of a few hundred-nanometer ranges, in which various biological modulating components such as peptides, mRNAs, and cytokines are encapsulated. According to the recent functional characterization of the organ-specific extracts, the individual groups of exosomes denote a myriad of roles in immune response, cancer therapy, diagnostics, and others. Among them, the nasal lavage fluid is known to contain exosomes that function as an immunological barrier in the airway epithelium of nasal cavity. In this study, we are able to obtain infinitesimal amounts of intact exosomes from the nasal lavage fluid of the Alzheimer’s disease (AD) model mouse, 5XFAD, by the pinched flow fractionation method. Nanoparticle tracking and biochemical analysis show the increase of the exosome concentration of the 5XFAD nasal lavage fluid. Likewise, the number of nanoparticles in the intact condition from 5XFAD is higher than that from the wild type animals on the transmission electron microscopy (TEM). To exam the functional implication in neurons, the cortical and hippocampal neurons from the P0 animal brain are prepared on the Biochip of the multielectrode array (HD-MEA) system with 4096 electrodes. Interestingly, the neural spike recording in the 5XFAD exosome treated MEA significantly accelerates the frequency of activation, escalating to the burst-tonic response from a random phasic pattern in the spontaneous synchrony activities. This response pattern resembles the result of the active amyloid-beta (Aβ) plaque treatment. In the organotypic hippocampal slice (OHS) recordings also represents similar results both in Aβ as well as 5XFAD exosome treatment. Finally, exosomes from wild type animals recover the neural activity to the normal condition. Therefore, the intact exosomes from the AD nasal lavage fluid functionally reflect the neurodegenerative disease symptoms in the neuronal level at the same time exosomes from healthy subject has a therapeutic potential.