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Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein.

Authors
Lee, KW; Im, JY; Song, JS; Lee, SH; Lee, HJ; Ha, HY; Koh, JY; Gwag, BJ; Yang, SD; Paik, SG; Han, PL
Citation
Neurobiology of disease, 22(1):10-24, 2006
Journal Title
Neurobiology of disease
ISSN
0969-99611095-953X
Abstract
The beta-secretase cleaved Abeta-bearing carboxy-terminal fragments (betaCTFs) of amyloid precursor protein (APP) in neural cells have been suggested to be cytotoxic. However, the functional significance of betaCTFs in vivo remains elusive. We created a transgenic mouse line Tg-betaCTF99/B6 expressing the human betaCTF99 in the brain of inbred C57BL/6 strain. Tg-betaCTF99/B6 mouse brain at 12-16 months showed severely down-regulated calbindin, phospho-CREB, and Bcl-xL expression and up-regulated phospho-JNK, Bcl-2, and Bax expression. Neuronal cell density in the Tg-betaCTF99/B6 cerebral cortex at 16-18 months was lower than that of the non-transgenic control, but not at 5 months. At 11-14 months, Tg-betaCTF99/B6 mice displayed cognitive impairments and increased anxiety, which were not observed at 5 months. These results suggest that increased betaCTF99 expression is highly detrimental to the aging brain and that it produces a progressive and age-dependent AD-like pathogenesis.
MeSH terms
Aging/geneticsAging/metabolism*Aging/pathologyAlzheimer Disease/geneticsAlzheimer Disease/metabolism*Alzheimer Disease/physiopathologyAmyloid beta-Peptides/geneticsAmyloid beta-Peptides/metabolismAmyloid beta-Protein Precursor/chemistryAmyloid beta-Protein Precursor/geneticsAmyloid beta-Protein Precursor/metabolism*AnimalsAnxiety Disorders/geneticsAnxiety Disorders/metabolismAnxiety Disorders/physiopathologyApoptosis/geneticsBehavioral Symptoms/geneticsBehavioral Symptoms/metabolismBehavioral Symptoms/physiopathologyBrain/metabolism*Brain/pathologyBrain/physiopathologyCell LineCognition Disorders/geneticsCognition Disorders/metabolismCognition Disorders/physiopathologyDisease Models, AnimalDisease ProgressionDown-Regulation/geneticsMiceMice, Inbred C57BLMice, TransgenicNerve Degeneration/geneticsNerve Degeneration/metabolism*Nerve Degeneration/physiopathologyNerve Tissue Proteins/metabolismPeptide Fragments/geneticsPeptide Fragments/metabolism*Protein Structure, Tertiary/geneticsSignal Transduction/geneticsUp-Regulation/genetics
DOI
10.1016/j.nbd.2005.09.011
PMID
16289866
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
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