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United States Department of Agriculture

Agricultural Research Service

Title: ALTERED EXPRESSION AND DISTRIBUTION OF ZINC TRANSPORTERS IN APP/PS1 TRANSGENIC MOUSE BRAIN

Authors
item Zhang, Li-Hong - CHINA MED. UNIVERSITY
item Wang, Xin - CHINA MED. UNIVERSITY
item Zheng, Zhi-Hong - CHINA MED. UNIVERSITY
item Ren, Hao - CHINA MED. UNIVERSITY
item Stoltenberg, Meredin - UNIV. OF ARAHUS, NEUROBIO
item Danscher, Gorm - UNIV. OF ARAHUS, NEUROBIO
item Huang, Liping
item Rong, Ming - CHINA MED. UNIVERSITY
item Wang, Zhan-You - CHINA MED. UNIVERSITY

Submitted to: Neurobiology of Aging
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 22, 2008
Publication Date: February 18, 2008
Repository URL: http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T09-4S69S0W-3-W&_cdi=4857&_user=4421&_pii=S0197458008000675&_origin=search&_coverDate=01%2F31%2F2010&_sk=999689998&view=c&wchp=dGLzVtz-zSkzS&md5=e5494e299ef9103a4e8dd9eaa2853339&ie=/sdarticle.pdf
Citation: Zhang, L., Wang, X., Zheng, Z., Ren, H., Stoltenberg, M., Danscher, G., Huang, L., Rong, M., Wang, Z. 2008. Altered expression and distribution of zinc transporters in app/ps1 transgenic mouse brain. Elsevier, Journal Neurobiology of Aging, Doi:10,1016:1-14, 2008.

Interpretive Summary: Abnormal accumulation of b-amyloid peptide (Ab, a short peptide that is an abnormal proteolytic byproduct of the amyloid precursor protein) is an early and common feature of Alzheimer’s disease (AD). Previous studies have revealed that an elevation of zinc concentration can initiate the deposition of Ab that leads to the formation of senile plaques (SP, extracellular deposits of amyloid) and cerebral amyloid angiopathy (CAA, amyloid deposits in the walls of the blood vessels of the brain.). However, little is known about the roles of zinc transporters (ZnTs) in these processes. In the present study, we detected zinc ions in the APPswe/PS1dE9 transgenic mice brain using immersion autometallography, and explored for the first time the distribution of ZnT1, ZnT3, ZnT4, ZnT5, ZnT6 and ZnT7 in the hippocampus (a part of the brain playing roles in memory, emotion, and spatial navigation and cortex (the outermost or superficial layer of the brain) by means of immunohistochemistry and double-immunofluorescence for the ZnTs and Ab amyloid. We found that all ZnTs were expressed in most amiloid plaques and amyloid angiopathic vessels, showing different staining pattern and staining intensities. ZnT1 and ZnT4 were extensively expressed in all parts of the plaque. ZnT3, ZnT5 and ZnT6 were expressed most prominently in the degenerating neurites (projections from the cell body of a neuron) in the periphery part of the plaques, while ZnT7 was present in the core of a multitude of the plaques. The CAA changed vascular walls showed a strong ZnT3 immunoreactivity. We further measured the level of ZnTs in the hippocampus and cortex using Western blot analysis. Results demonstrated statistically significant (P<0.05) elevations of ZnT1, 3, 4, 6, 7 in both hippocampus and cortex. ZnT5 was also increased (P<0.1) in the hippocampus and cortex. In conclusion, the present study shows the elevations of ZnTs in both hippocampus and cortex and an abundant expression of ZnTs in the amyloid plaque and CAA changed blood vessels, suggests a role of ZnTs in the neuron degeneration and the pathological accumulation of Ab.

Technical Abstract: Pathological accumulation of b-amyloid peptide (Ab) is an early and common feature of Alzheimer’s disease (AD). Previous studies have revealed that an elevation of zinc concentration can initiate the deposition of A' that leads to the formation of senile plaques (SP) and cerebral amyloid angiopathy (CAA). However, little is known about the roles of zinc transporters (ZnTs) in these processes. In the present study, we detected zinc ions in the APPswe/PS1dE9 transgenic mice brain using immersion autometallography, and explored for the first time the distribution of ZnT1, ZnT3, ZnT4, ZnT5, ZnT6 and ZnT7 in the hippocampus and cortex by means of immunohistochemistry and double-immunofluorescence for the ZnTs and Ab amyloid. We found that all ZnTs were expressed in most amiloid plaques and amyloid angiopathic vessels, showing different staining pattern and staining intensities. ZnT1 and ZnT4 were extensively expressed in all parts of the plaque. ZnT3, ZnT5 and ZnT6 were expressed most prominently in the degenerating neurites in the periphery part of the plaques, while ZnT7 was present in the core of a multitude of the plaques. The CAA changed vascular walls showed a strong ZnT3 immunoreactivity. We further measured the level of ZnTs in the hippocampus and cortex using Western blot analysis. Results demonstrated statistically significant (P<0.05) elevations of ZnT1, 3, 4, 6, 7 in both hippocampus and cortex. ZnT5 was also increased (P<0.1) in the hippocampus and cortex. In conclusion, the present study shows the elevations of ZnTs in both hippocampus and cortex and an abundant expression of ZnTs in the amyloid plaque and CAA changed blood vessels, suggests a role of ZnTs in the neuron degeneration and the pathological accumulation of Ab.

Last Modified: 9/1/2014
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