Intrahippocampal injection of Aβ1-42inhibits neurogenesis and down-regulates IFN-γ and NF-κB expression in hippocampus of adult mouse brain
Autor: | Jing Liu, Zhigang Ruan, Meige Zheng, Sumin Tian, Jiayong Zhu, Guoying Li, Yuxin Ma |
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Rok vydání: | 2013 |
Předmět: |
Male
medicine.medical_specialty Neurogenesis Central nervous system Gene Expression Hippocampus Hippocampal formation Biology Subgranular zone Interferon-gamma Mice Neural Stem Cells Alzheimer Disease Internal medicine Internal Medicine medicine Animals Humans Injections Intraventricular Mice Inbred BALB C Amyloid beta-Peptides Dentate gyrus Neurodegeneration NF-kappa B Long-term potentiation Anatomy medicine.disease Peptide Fragments medicine.anatomical_structure Endocrinology |
Zdroj: | Amyloid. 20:13-20 |
ISSN: | 1744-2818 1350-6129 |
DOI: | 10.3109/13506129.2012.755122 |
Popis: | 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. |
Databáze: | OpenAIRE |
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