Amyloid β Is Not the Major Factor Accounting for Impaired Adult Hippocampal Neurogenesis in Mice Overexpressing Amyloid Precursor Protein.
Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP). However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid β (Aβ) or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG) of adult mice overexpressing wild-type hAPP (hAPP-I5) compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aβ. Furthermore, reducing Aβ levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aβ was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Hongyu
H
Pan
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Dongpi
D
Wang
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Xiaoqin
X
Zhang
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Dongming
D
Zhou
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Heng
H
Zhang
Department of Neurology, Brain Medical Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Qi
Q
Qian
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Xiao
X
He
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Zhaoling
Z
Liu
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Yunjin
Y
Liu
Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Tingting
T
Zheng
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Ling
L
Zhang
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Mingkai
M
Wang
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China. Electronic address: bsun@zju.edu.cn.
Binggui
B
Sun
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
Alzheimer’s disease; adult neurogenesis; amyloid β; hAPP; hippocampus; mouse
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