Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein.
Neurofibrillary tangles (NFTs) are a pathological hallmark of many neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP17). However, the cellular origin and the consequence of the NFT formation are poorly understood. Epidemiological evidence suggests a much higher occurrence of dementia in stroke patients. This may represent the pathogenesis of sporadic AD, which accounts for the majority of AD occurrence. Here we show that after a transient cerebral ischemia, hyperphosphorylated tau accumulates in cortical neurons in a site-specific manner. The hyperphosphorylated tau presents a conformation similar to those present in human tauopathies, and colocalizes largely with signs of apoptosis. Our current study suggests that tau hyperphosphorylation may contribute to the brain damage induced by transient cerebral ischemia, and may be involved in the pathogenesis of neurodegenerative disorders in patients after stroke. Further, these results indicate that ischemic neuronal damage and apoptosis associates with tau hyperphosphorylation, and potentially NFTs formation. Finally, our results also suggest that neuronal apoptosis may be a therapeutic target in preventing tauopathy-related neurodegenerative diseases.
Wen
Yi
Y
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA.
Yang
Shaohua
S
Liu
Ran
R
Simpkins
James W
JW
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D013778:Tetrazolium Salts; D016875:tau Proteins
D000911:Antibodies, Monoclonal; D007211:Indoles; C489131:Mapt protein, rat; D009419:Nerve Tissue Proteins; C085349:PHF-1 monoclonal antibody; D013778:Tetrazolium Salts; D016875:tau Proteins; C007293:DAPI; C009591:triphenyltetrazolium