Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw

Dae Y Hwang; Jung S Cho; Su H Lee; Kab R Chae; Hwa J Lim; Sea H Min; Su J Seo; Youn S Song; Chi W Song; Sang G Paik; Yhun Y Sheen; Yong K Kim

doi:10.1016/j.expneurol.2003.09.021

Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw

Exp Neurol. 2004 Mar;186(1):20-32. doi: 10.1016/j.expneurol.2003.09.021.

Authors

Dae Y Hwang¹, Jung S Cho, Su H Lee, Kab R Chae, Hwa J Lim, Sea H Min, Su J Seo, Youn S Song, Chi W Song, Sang G Paik, Yhun Y Sheen, Yong K Kim

Affiliation

¹ Division of Laboratory Animal Resources, Korea FDA, National Institute of Toxicological Research, Seoul 122-704, South Korea.

PMID: 14980807
DOI: 10.1016/j.expneurol.2003.09.021

Abstract

Mutations in the APP gene lead to enhanced cleavage by the beta- and gamma-secretase, and increased Abeta formation, which are tightly associated with Alzheimer's disease (AD)-like neuropathological changes. To examine whether depositions of Abeta by APP mutations are increased, and if this is associated with potential pathogenic phenotypes, the APPsw was expressed in a transgenic line under the control of the neuron-specific enolase (NSE) promoter. A behavioral dysfunction was shown at 12 months, and intensive staining bands, with APP and Abeta-42 antibodies, were visible in the brains of transgenic mice. Of the MAPK family, both JNK and p38 were activated in the brains of transgenic mice, whereas there was no significant activation of the ERK. In parallel, tau phosphorylation was also enhanced in the transgenic relative to the control mice. Moreover, the Cox-2 levels, from Western blot and immunostaining, were increased in the brains of the transgenic line. Furthermore, there were significant caspase-3- and TUNEL-stained nuclei in the transgenic line compared to the age-matched control mice. Thus, these results suggest that NSE-controlled APPsw transgenic mice appear to be a more relevant model in neuropathological phenotypes of AD, and thus could be useful in developing new therapeutic treatments for targeting the aberrant phenotypes that appear in these mice.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / genetics
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism
Amyloid beta-Protein Precursor / genetics*
Animals
Apoptosis / genetics
Behavior, Animal
Blotting, Western / methods
Brain / anatomy & histology
Brain / metabolism
Caspase 3
Caspases / metabolism
Cyclooxygenase 2
DNA / metabolism
Disease Models, Animal
Escape Reaction / physiology
Immunoblotting / methods
Immunohistochemistry / methods
In Situ Nick-End Labeling / methods
Isoenzymes / metabolism
JNK Mitogen-Activated Protein Kinases*
MAP Kinase Kinase 4
Mice
Mice, Transgenic
Mitogen-Activated Protein Kinase Kinases / metabolism
Mitogen-Activated Protein Kinases / metabolism
Molecular Sequence Data
Mutation
Peptide Fragments / metabolism
Phenotype*
Phosphopyruvate Hydratase / genetics
Phosphopyruvate Hydratase / physiology*
Prostaglandin-Endoperoxide Synthases / metabolism
RNA, Messenger / biosynthesis
Reaction Time / genetics
Reverse Transcriptase Polymerase Chain Reaction / methods
p38 Mitogen-Activated Protein Kinases
tau Proteins / metabolism

Substances

Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Isoenzymes
Peptide Fragments
RNA, Messenger
amyloid beta-protein (1-42)
tau Proteins
DNA
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4
Mitogen-Activated Protein Kinase Kinases
Casp3 protein, mouse
Caspase 3
Caspases
Phosphopyruvate Hydratase