Abstract
This study aimed to investigate the neurotoxicity of exosomes to cultured neuroblastoma and neurons in vitro and to mature and newborn neurons in the hippocampus in vivo. Recent in vitro and in vivo studies have shown that exosomes, small membranous vesicles secreted from many cell types, contain pathogenic proteins including full-length amyloid precursor protein (flAPP) and amyloid precursor protein (APP) metabolites. However, the function of these exosomes in Alzheimer disease (AD) has not been much explored. In the present study, exosomes were harvested from the conditioned medium of HEK293-APP Swe/Ind cells and injected into the hippocampal dentate gyrus region via a stereotactic method to detect their effects on the neuronal survival in vivo. These exosomes containing pathogenic proteins showed high neurotoxicity and could impair neurogenesis in the hippocampus. The data demonstrated that exosomes secreted from sick cells might damage neurogenesis and promote disease progression in AD.
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Abbreviations
- FlAPP:
-
Full-length amyloid precursor protein
- DG:
-
Hippocampal dentate gyrus
- CTFs:
-
C-terminal fragments
- MVBs:
-
Multivesicular bodies
- NDEs:
-
Neuronal derived exosomes
- TEM:
-
Transmission electron microscope
- NTA:
-
Nanoparticle tracking analysis
- DCX:
-
Doublecortin
- APP-EXO:
-
Exosomes harvested from HEK cells expressing APP Swe/Ind
- EXO:
-
Exosomes harvested from HEK cells transfected with null vector
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Acknowledgements
We thank Edward Koo for CT15 antibody and Dennis Selkoe and Tracy Young-Pearse for pCAX APP Swe/Ind. This work was supported by grants from the National 973 Project (grant numbers 2013CB530900 and 2013CB530904), the National Nature Science Foundation of China (grant numbers 81400866 and 81400933), and the Nature Science Foundation of Zhejiang Province(LY17H090005). They also thank the Institute of Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, China, for institutional support.
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Zheng, T., Pu, J., Chen, Y. et al. Exosomes Secreted from HEK293-APP Swe/Ind Cells Impair the Hippocampal Neurogenesis. Neurotox Res 32, 82–93 (2017). https://doi.org/10.1007/s12640-017-9713-1
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DOI: https://doi.org/10.1007/s12640-017-9713-1