A fundamental characteristic of the hypometabolic state during mammalian hibernation regardless of the different physiological characteristics of hibernation. In addition to hibernation, increased tau phosphorylation has also been reported during starvation, anaesthesia, and cold water stress, conditions which all are associated with a reduced body temperature. Planel and co-workers suggested that due to differences in temperature dependency of kinetics for tau kinases and tau phosphatases, lower body temperature ultimately Dexrazoxane hydrochloride results in increased levels of phospho-tau. Therefore, in our study, we addressed the Butenafine hydrochloride question whether the observed increase in tau-phosphorylation during hibernation might simply be due to such passive, temperature-driven mechanism, or if in addition, hibernation-related specific regulatory mechanism might be involved. The results of the phospho-protein stain revealed only a tendency towards increased phospho-protein concentration in the state of torpor. Considering the number of potential phosphoproteins and the intense phospho-tau level in hibernation this finding does not support a shift towards a generally increased kinase activity at lower body temperatures and indicates specific regulatory mechanisms in addition. This is corroborated by the results of the net phosphate turnover assay of tau protein. Overall, our results correspond to findings of previous studies showing that a decreased body temperature results in the formation of highly phosphorylated tau. Characteristics of this dependency of tau-phosphorylation on temperature, however, markedly differed, depending on whether tissue was taken from torpid, aroused or euthermic animals. At comparable temperatures, phosphate incorporation into tau was much facilitated in tissue from torpid animals compared to euthermic animals. This indicates the existence of a specific component in the regulation of tau phosphorylation at early stages of hibernation when animals enter into torpor. The analysis of site-specific differences in the kinetics of tau phosphorylation and dephosphorylation showed that in general tau phosphosites were already highly phosphorylated in early torpor and the degree of phosphorylation did not increase further in the course of torpor. Nevertheless, the phosphosite T231/S235 is subject to aberrant phosphorylation kinetics. The phosphodegree of this site significantly increased with progression of torpor in arctic ground squirrels and Syrian hamsters, respectively, indicating a substantially different regulation. However, based on the significant overlap with respect to the kinases and phosphatases that are involved in the regulation of phosphorylation/dephosphorylation of the investigated individual sites it is intricate to denote the underlying mechanisms. Our results do not show any indication of a differentially regulated site-specific dephosphorylation of tau after arousal. We found a significantly elevated phosphorylation after late arousal only in the midbrain for the phosphosites T181 and S396/404 and in the brainstem for S396. In each of the other brain regions investigated all phosphosites showed a level not different from the euthermic state. These results are at variance to those of Su and co-workers who reported that the phosphosites T205, S214 and S396 remain phosphorylated after arousal in arctic ground squirrels. Our results demonstrate a progressive 
decrease of phospholevels from late torpor to early arousal and furthermore to late arousal with site-specific differences in dephosphorylation rates. This is supported by findings demonstrating site-specific dephosphorylation kinetics of tau protein. In the present study we observed an equipollent tau phosphorylation pattern involving phosphosites that have been demonstrated being affected in both early and late stages of AD. The involvement of the tau phosphosites T231/S235 and T212/S214/ T217 respectively is remarkable since they are suggested to be directly related to pathological processes.