FAM19A5 is a rostral-caudal organizer in the mouse cortex development

摘要

Differential expression profiling of exosomal mitochondrial components in the developmental disorder Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells. Since exosomes include tissue-specific and disease-related molecules such as lipids, proteins and RNAs, they are considered as emerging tools for biomarkers screening and drug/gene delivery in diagnostic and therapeutic strategies. In cen- tral nervous system, they have a functional impact on physiological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication and neurogenesis. While several groups have reported that exosomes can transfer pathogens such as prion protein (PrP), w-synuclein, amyloid B (AB) and phosphorylated tau, research regarding their role in developmental disorders remains scarce. In this study, we performed the protein profiling in exo- some derived from either the cortex or primary neuron/astrocyte of the developmental disorders mouse model. Various mitochondrial components were detected in exosomes isolated from the cortex and primary neuron/astrocyte prepared from the mouse model. Our findings show that mitochondrial proteins were remarkably decreased in disease mouse models which was confirmed by anal- ysis with western blot, mitotracker and qRT-PCR for mtDNADNA ratio as well as gene expression related to mitochondrial biogen- esis. Moreover, from neuron and astrocytes in both normal and disease, changes of mitochondrial membrane potential as a marker for mitochondrial activity and neuronal viability were observed. In conclusion, these results suggest that the interplay between mitochondria and exosome is altered under the developmen- tal dysfunction and exosomes-derived mitochondrial components have a possibility as potential diagnostic/prognostic/therapeutic targets.