Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/137257
Title: Tau-positive nuclear indentations in P301S tauopathy mice
Author: Fernández-Nogales, Marta
Santos-Galindo, María
Merchán-Rubira, Jesús
Hoozemans, Jeroen
Rábano, Alberto
Ferrer, Isidro (Ferrer Abizanda)
Avila, Jesús
Hernández, Félix
Lucas, José J.
Keywords: Nuclis cel·lulars
Metabolisme
Patologia
Ratolins (Animals de laboratori)
Cell nuclei
Metabolism
Pathology
Mice (Laboratory animals)
Issue Date: May-2017
Publisher: Wiley
Abstract: Increased incidence of neuronal nuclear indentations is a well-known feature of the striatum of Huntington's disease (HD) brains and, in Alzheimer's disease (AD), neuronal nuclear indentations have recently been reported to correlate with neurotoxicity caused by improper cytoskeletal/nucleoskeletal coupling. Initial detection of rod-shaped tau immunostaining in nuclei of cortical and striatal neurons of HD brains and in hippocampal neurons of early Braak stage AD led us to coin the term 'tau nuclear rods (TNRs).' Although TNRs traverse nuclear space, they in fact occupy narrow cytoplasmic extensions that fill indentations of the nuclear envelope and we will here refer to this histological hallmark as Tau-immunopositive nuclear indentations (TNIs). We reasoned that TNI formation is likely secondary to tau alterations as TNI detection in HD correlates with an increase in total tau, particularly of the isoforms with four tubulin binding repeats (4R-tau). Here we analyze transgenic mice that overexpress human 4R-tau with a frontotemporal lobar degeneration-tau point mutation (P301S mice) to explore whether tau alteration is sufficient for TNI formation. Immunohistochemistry with various tau antibodies, immunoelectron microscopy and double tau-immunofluorescence/DAPI-nuclear counterstaining confirmed that excess 4R-tau in P301S mice is sufficient for the detection of abundant TNIs that fill nuclear indentations. Interestingly, this does not correlate with an increase in the number of nuclear indentations, thus suggesting that excess total tau or an isoform imbalance in favor of 4R-tau facilitates tau detection inside preexisting nuclear indentations but does not induce formation of the latter. In summary, here we demonstrate that tau alteration is sufficient for TNI detection and our results suggest that the neuropathological finding of TNIs becomes a possible indicator of increased total tau and/or increased 4R/3R-tau ratio in the affected neurons apart from being an efficient way to monitor pathology-associated nuclear indentations.
Note: Versió postprint del document publicat a: https://doi.org/10.1111/bpa.12407
It is part of: Brain Pathology, 2017, vol. 27, num. 3, p. 314-322
URI: http://hdl.handle.net/2445/137257
Related resource: https://doi.org/10.1111/bpa.12407
ISSN: 1015-6305
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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