Functional study in the young rTg4510 mouse model of tauopathy

Abstract Background Tau hyperphosphorylation (pTau) is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, pTau promotes neuroprotection by preventing seizure‐like activity. Method To further support the notion that very early pTau is not detrimental, the present work evaluated the young rTg4510 mouse model of tauopathy as a case study. Thus, in mice at one month of age (p30‐35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. Result Our results showed that the very young rTg4510 model has no detectable changes in hippocampal dependent tasks, such as spontaneous alternation and nesting, or in locomotor activity. However, at this very early stage the hippocampal neurons from p30‐35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found an increased number of dendrites per cell in granule neurons. Conclusion Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.