Affiliations: [a] UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico | [b]
CONACYT National Council for Science and Technology, Mexico City, Mexico | [c] UTSA Neuroscience Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA
Correspondence:
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Correspondence to: Siddhartha Mondragón Rodríguez, Developmental Neurobiology and Neurophysiology, UNAM, Boulevard Juriquilla 3001, Juriquilla, 76230 Santiago de Querétaro, Qro, México. Tel.: +52 442 238 1057; E-mail: smondragonro@conacyt.mx.
Abstract: Background:Tau hyperphosphorylation at several sites, including those close to its microtubule domain (MD), is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, tau phosphorylation (pTau) at MD sites promotes neuroprotection by preventing seizure-like activity. Objective: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 (PN30-35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. Methods:We used immunohistochemistry, T-maze, nesting test, novel object recognition test, open field arena, and electrophysiology. Results:Our results showed that the very young rTg4510 mouse 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 PN30-35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found a significant reduction in the somatic area of pTau positive pyramidal and granule neurons in the young rTg4510 mice. Despite this, improved memory and increased number of dendrites per cell in granule neurons was found. Conclusion:Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.
