title: Intrahippocampal injection of Aβ1-42 inhibits neurogenesis and down-regulates IFN-γ and NF-κB expression in hippocampus of adult mouse brain.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by accumulation of amyloid plaques and neurofibrillary tangles. Amyloid-β (Aβ) is widely recognized as a key factor in the pathogenesis of AD. Aβ1-42 a major component of amyloid plaques, has shown synaptotoxicity associated with impaired long-term potentiation and cognitive deficits. Alteration of neurogenesis in AD patients has been reported, while little is known about how Aβ1-42 affects hippocampal neurogenesis in the adult brain. In this study, we injected human Aβ1-42 peptide into hippocampal CA1 area of adult mouse brain bilaterally and evaluated histological change and neurogenesis in the hippocampus. Hematoxylin and eosin (HE) stain showed that Aβ1-42-injection resulted in an extensive neurodegeneration in the Aβ-accumulated area and CA3 in hippocampus. Immunostaining showed that intrahippocampal Aβ1-42-injection dramatically decreased the number of bromodeoxyuridine (BrdU)-positive cells in the dentate gyrus (DG) compared to the vehicle injection. Moreover, a significant decrease in the number of BrdU/double-cortin double-positive cells in Aβ1-42-injected hippocampus was observed, suggesting that Aβ1-42-injection inhibited progenitor cell proliferation and neurogenesis in subgranular zone of the DG in the adult brain. We also found that the Aβ1-42-mediated decline of neurogenesis was associated with decreased protein levels of cytokines interferon-γ (IFN-γ) and transcription factor nuclear factor-kappa B (NF-κB) in the hippocampus. These results suggest that Aβ1-42 inhibits hippocampal neurogenesis in the adult brain possibly through down-regulation of INF-γ and NF-κB signaling pathway. This study provides a new insight into Aβ1-42-mediated decrease in hippocampal neurogenesis in the adult central nervous system.
authors.affiliation: Department of Anatomy, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Meige
authors.initials: M
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Ruan
authors.forename: Sumin
authors.initials: S
authors.lastname: Tian
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Jiayong
authors.initials: J
authors.lastname: Zhu
authors.forename: Guoying
authors.initials: G
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007276:Injections, Intraventricular; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D016328:NF-kappa B; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007371:Interferon-gamma