engleski

The possibility for development of non-transgenic rat tauopathy model by application of tau oligomers into the entorhinal cortex

Introduction: Alzheimer's disease (AD) is the most common secondary tauopathy characterized by progressive loss of cognitive functions and behavioral impairment. Materials and Methods: Four-month-old male Wistar rats were stereotaxically injected into the entorhinal cortex with pathological tau oligomers, tau fibrils, and PBS (phosphate-buffered saline). Animals were tested, sacrificed, and analyzed 4, 8, and 11 months post-injection. Cognitive performance testing included T-maze, novel object recognition test, and object location test. To detect specific tau protein changes and perform staging of tau pathology, we used several anti-tau monoclonal antibodies. Proteins isolated from the entorhinal cortex and hippocampus were analyzed by immunoblotting. Results: The obtained results suggested that the stereotaxic injection of pathological tau oligomers or tau fibrils into the lateral entorhinal cortex induced phosphorylation of Ser202/Thr205 tau epitope. Using the HT7 antibody, which recognizes human tau protein, we also found a signal present in the brainstem and transentorhinal region. Rewarded learning in the T-maze showed learning curve with more incorrect choices in rats injected with tau fibrils. Conclusion: Understanding of the role of tau oligomers and tau fibrils in this rat model of neurodegeneration has a great potential for revealing mechanisms underlying development and progression of AD in humans.

Alzheimer's disease ; animal model ; cognitive impairment ; entorhinal cortex ; tauopathy ; tau proteins

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