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P3‐286: Hypoperfusion‐Induced TAU Hyperphosphorylation Extends to the Non‐Hypoperfused Area in Mouse Brain
Author(s) -
Fujita Youshi,
Hamano Tadanori,
Shirafuji Norimichi,
Nakamoto Yasunari
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1950
Subject(s) - corpus callosum , white matter , pathology , hyperphosphorylation , perfusion , medicine , neuroscience , cognitive decline , brain damage , vascular dementia , tau protein , dementia , alzheimer's disease , biology , magnetic resonance imaging , phosphorylation , disease , microbiology and biotechnology , radiology
Background: Hyperphosphorylation and pathological aggregation of tau and axonal damage is a common feature of many neurodegenerative diseases including Alzheimer’s disease. However, the contribution of cerebral hypoperfusion to tau hyperphosphorylation accompanied by axonal damage remains unclear. Recent study indicates that incident stroke was associated with acute decline in cognitive function and also accelerated and persistent cognitive decline. We hypothesized that hypoperfusion-induced tau hyperphosphorylation may propagate to the non-hypoperfused area. Methods: Adult C57Bl/6 male mice were subjected to unilateral common carotid artery occlusion (UCCAO), which induces chronic cerebral hypoperfusion in the hemisphere ipsilateral to UCCAO; a mouse model of vascular dementia with white matter lesions. The brains of the mice were analyzed by immunohistochemistry and immunoblotting to detect phosphorylated tau and axonal changes after the surgery. Results:Hosphorylated tau was increased in cortical neurons in the hemisphere ipsilateral to the UCCAO. Moreover, phosphorylated tau was increased in the contralateral hemisphere with a difference in the time course. White matter rarefaction was observed in the corpus callosum, where the number of Iba-1-immunopositive microglia and GFAP-immunopositive astroglia increased after the surgery. The number of SMI311-immunopositive fibers decreased in the ipsilateral corpus callosum, which indicated axonal damage within the white matter lesion after chronic cerebral hypoperfusion. Conclusions:The results indicate that cerebral hypoperfusion induces tau hyperphosphorylation accompanied by axonal damage in adult mice. Moreover, indicating that there is interhemispheric propagation of hypoperfusion-induced tau hyperphosphorylation in mouse brain.