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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.
We determined CA1 hippocampal field to be involved in self‑exposure, a type of novelty‑seeking behaviour that has also been associated with short 22 kHz and flat 50 kHz ultrasonic vocalizations (USV) in adult male Long‑Evans rats. Rats were habituated for three days to a self‑exposure cage with two nose‑poke holes. On day four, the animals from the experimental group were allowed to turn the cage light off for 5 s with a nose‑poke (test/self‑exposure session), while rats from control‑yoked group had changing light conditions coupled and identical to the experimental animals. The experimental rats performed more nose‑pokes during self‑exposure session than animals from the control group. This effect was accompanied by a higher density of c‑Fos‑positive nuclei in the hippocampal CA1. There were no significant group differences in c‑Fos expression in other brain regions analysed. However, possible involvement of several other structures in self‑exposure (i.e., CA3, the dentate gyrus, amygdala, prefrontal cortex, and nucleus accumbens) is also discussed, as their correlational activity, reflected by c‑Fos immunoactivity, was observed in the experimental rats. During test sessions, there were more nose‑pokes accompanied by short 22 kHz calls and 50 kHz calls performed by the rats of the experimental group than of the control group. The CA1 region has previously been associated with novelty; short 22 kHz USV and flat 50 kHz USV could be associated with self‑exposure, also they appear to be emitted correlatively.
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