Exosomes Secreted from HEK293-APP Swe/Ind Cells Impair the Hippocampal Neurogenesis.
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.
Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
Tingting
T
Zheng
Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
Jiali
J
Pu
Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
Yanxing
Y
Chen
Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
Zhangyu
Z
Guo
Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Hongyu
H
Pan
Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Ling
L
Zhang
Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Heng
H
Zhang
Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China. bsun@zju.edu.cn.
Binggui
B
Sun
Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China. brzhang@zju.edu.cn.
Baorong
B
Zhang
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D055354:Exosomes / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D017304:Annexin A5; D002135:Calcium-Binding Proteins; C492143:Pdcd6ip protein, rat; D001973:Bromodeoxyuridine
APP; Exosomes; HEK293-APPSwe/Ind cells; Neurogenesis; Neurotoxicity