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. 2019 Oct 24;10:1269. doi: 10.3389/fphys.2019.01269

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Copyright © 2019 Denver, D’Adamo, Hu, Zuo, Zhu, Okuma, Kim, Castro, Jones, Leal, Mekkittikul, Ghadishah, Teter, Vinters, Cole and Frautschy.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Tau staining and insoluble protein levels are increased in SHRSP/FAD rats. Micrographs depict positive tau pS422 staining in the hilus of the hippocampus of WKY (n = 8), FAD (n = 11), SHRSP (n = 10), and SHRSP/FAD (n = 9) rats. Only SHRSP/FAD rats showed intense staining of neurons labeling globose neurofibrillary tangle-like structures extending tortuous neurites. Two-way ANOVA of percent area and cell size showed significant main effects of SHRSP (p = 0.001, p = 0.006), FAD (p = 0.0001, p = 0.0001) and SHRSP × FAD interactions (p = 0.025, p = 0.034), respectively. Percentage area stained positive for tau pS422 was increased more than two-fold in the SHRSP/FAD rats, compared to WKY, FAD and SHRSP rats (p < 0.0001). Post hoc analysis indicated that cell size was significantly elevated in the hilus of FAD rats, compared to WKY (p < 0.01), while further elevations of tau pS422 cell size were detected in SHRSP/FAD rats, compared to FAD and SHRSP rats (p < 0.001). The lower right panel shows representative lanes from a western blot analysis of CP13, an antibody to the serine 202 phospho-epitope of tau from the insoluble SDS fractions of hippocampal lysates. Two-way ANOVA showed a significant FAD effect and a FAD × SHR interaction. Post hoc analysis showed that there was a non-significant trend for increased CP13 levels in hippocampus from FAD compared to WKY rats (p = 0.08). However, in SHRSP/FAD rats, levels were significantly elevated compared to SHRSP rats (p < 0.001). Furthermore, CP13 levels were significantly elevated in the hippocampus of SHRSP/FAD rats, compared to FAD (p < 0.05). Data represent means ± SEM. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001; two-way ANOVA with LSD Fisher’s post hoc test.