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Abnormal APP, cholinergic and cognitive function in Ts65Dn Down`s model mice

Title
Abnormal APP, cholinergic and cognitive function in Ts65Dn Down`s model mice
Author
서혜명
Keywords
cognition; cholinergic transmission; APP processing; NGF expression; muscarinic agonist; septohippocampal function
Issue Date
2005-06
Publisher
ACADEMIC PRESS INC
Citation
EXPERIMENTAL NEUROLOGY, v. 193, No. 2, Page. 469-480
Abstract
We evaluated Ts65Dn Down's syndrome mice and their littermates (LM) at 12, 4, and 12 months of age to determine amyloid precursor protein (APP)-related cellular and biochemical changes associated with cognitive deficits. Ts65Dn mice showed cognitive deficits in the Morris water maze compared to LM mice at 4 and 12 months of age. Ts65Dn, but not LM mice, developed a septohippocampal cholinergic neuronal degeneration of choline acetyltransferase (ChAT)-positive neurons at 12 months of age. These cellular changes were compensated by increases in ChAT enzyme activity of remaining cholinergic terminals in the hippocampus. By 12 months of age, Ts65Dn mice had elevations of APP protein levels in the hippocampus compared to their LM. At this age, both Ts65Dn mice and their LM abnormally responded to cholinergic muscarinic M1 agonist treatment in terms of hippocampal APP, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels compared to young adult C57BL/6 mice. In summary, the Ts65Dn mice show developmental and progressive age-related behavioral deficits, hippocampal APP, and cholinergic pathology. The relatively better cognitive spatial performance in LM compared to Ts65Dn mice suggests that high APP levels combined with progressive degeneration of the cholinergic system are critical to the pathology and cognitive deficits seen in Ts65Dn mice. (c) 2004 Elsevier Inc. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0014488604004352http://repository.hanyang.ac.kr/handle/20.500.11754/110895
ISSN
0014-4886; 1090-2430
DOI
10.1016/j.expneurol.2004.11.017
Appears in Collections:
COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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