Tauopathies are a class of neurodegenerative diseases resulting from the pathological aggregation of tau protein in brain. The best known of these disorders is Alzheimer’s disease, where tau protein is deposited within neurons in the form of neurofibrillary tangles, which are formed by hyperphosphorylation of this microtubule-associated protein. Good animal model that mimic this form of age-related disease is still missing. Such a model should be characterized by: over expression, hyperphosphorylation and different cellular compartmentalization of tau in neurons, breakdown of cytoskeleton and malfunctioning of neuronal transport, and impairment of cognitive processes. We propose to develop such a model by local administration of full length tau directly into CA1 area of hippocampus in rats. Using specific pore-forming agent poly-APS we delivered tau protein through the membrane into the neurons where it is metabolized and may influence cognitive processes. Additional chronic administration of okadaic acid, a specific phosphatase inhibitor, caused tau hyperphosphorylation. Because tauopathies are age-related disorders, in our experiment we used several age-groups of animals to determine the age, in which we can provoke the morphological and cognitive impairments characteristic for tauopathy. Cognitive and neurodegenerative changes were examined with behavioral test and immunohistochemical techniques. Our data indicate that use of poly-APS enables for neuronal tau incorporation at selective brain site resulting in accelerated neurofibrillary tangle-like pathology. The major advance in the development of current tauopathy model is the determination of critical age at which it is possible to trigger morphological and cognitive impairments. This model mimics several pathologies observed in progressive dementia and could be successfully used in drug discovery to support therapeutic strategies.
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