Ident at high magnification. This is as expected as MC1 detects

The observed differences in pathology may be due to several factors, such as a reduction in the transgene copy number, promoter Whilst bigger patient sample sizes are necessary to demonstrate system improvements methylation, or the cleanliness of the facility the animals are housed title= SART.S23503 in. The same analyses were performed for 6B2 and IgG treated mice with average chemiluminescent signal for PHF-1 being 327,492 ?92,674 and 322,075 title= fpsyg.2016.00135 ?84,285 (p = 0.84) and for Tau-5 567,725 ?179,647 and 549,867 ?159,106 (p = 0.86), respectively. For all blots prepared using low speed supernatant samples, chemiluminescent signal was normalized using GAPDH (Fig. 3). There was minor variation in some samples, but GAPDH blots showed no significant difference between the control and treated groups. Two bands are visible on the representative blot prepared from the 4E6 study, whereas only one band is visible in the 6B2 study. This is likely due to differences in running time between blots.Mechanistic in vitro and ex vivo studiesTo further clarify the mechanisms of the positive effects of 4E6 and lack thereof for 6B2, various in vitro and ex vivo experiments were performed.Congdon et al. Molecular Neurodegeneration (2016):Page 4 ofFig. 2 Neither tau antibody led to benefits in a fear conditioning test or affected motor performance. a Treatment benefits were not observed in a fear conditioning test for a 4E6 or b 6B2, which relies on different brain circuits than the navigational test, or in motor tests (c-j), which were performed to verify that the cognitive benefits cannot be explained by confounding changes in motor performance. As expected, mice from both treated and control groups generally performed better on their post-treatment motor tests because of their pre-treatment training.Ident at high magnification. This is as expected as MC1 detects earlier tau pathology than PHF-1. There were no apparent differences between the treatment groups. Overall, we have observed a slower development, and less extensive pathology in this model compared to the initial report [20]. The observed differences in pathology may be due to several factors, such as a reduction in the transgene copy number, promoter methylation, or the cleanliness of the facility the animals are housed title= SART.S23503 in. There may also be selection effects, where animals with less pathology produce larger litters and become overrepresented in the colony. Other researchers have observed a lessening of pathological severity over time, or spontaneous loss of phenotype in transgenic lines [21, 22]. Likewise, no significant differences were seen via Western blot using CP27 in either the total tau low speed supernantant, or in sarkosyl insoluble tau for either antibody (Fig. 3a ). Tau-5, an additional total tauantibody, also showed no significant differences (Fig. 3e, f ). However, acute 4E6 treatment significantly reduced soluble PHF-1 reactive tau (48 reduction; p = 0.037, Fig. 3g), whereas 6B2 did not (Fig. 3h) . This beneficial effect of the therapy was not gender related (two-way ANOVA; gender effect (p = 0.905), and did not appear to be oligomer specific as T22 did not reveal any differences between the 4E6 and IgG groups (Fig. 3i). Sarkosyl insoluble fractions were also probed with PHF-1 and Tau-5, with no significant differences seen between antibody and IgG treated animals for either 4E6 or 6B2.