Journal: Alzheimer's & Dementia
Article Title: PP2A methylesterase, PME‐1, and PP2A methyltransferase, LCMT‐1, control sensitivity to impairments caused by injury‐related oligomeric tau
doi: 10.1002/alz.70947
Figure Lengend Snippet: Blast tau impairs cognition and synaptic plasticity in an oligomerization‐dependent manner. (A) Graph representing TOC1 normalized to total tau based on sandwich enzyme linked immunosorbent assay (sELISA) shows a significant difference between tau isolated from shockwave‐exposed mice (blast tau) and tau isolated from sham‐exposed mice (sham tau) (unpaired, one‐tailed t test: t = 2.254, p = 0.0239). N = 6 sham tau, six blast tau. (B) Number of errors committed during testing on a 2‐day radial arm water maze task for mice infused with sham or blast tau that was de‐oligomerized by treatment with reducing reagent alone (de‐oligo) or de‐oligomerized then re‐oligomerized by peroxide treatment (re‐oligo). Two‐way repeated measures (RM) ANOVA for errors on day 2 (blocks 6 to 10) with group and block as factors shows a significant effect of group (F[346] = 10.47, p < 0.0001), and Dunnett's post hoc comparisons show that re‐oligomerized blast tau‐treated mice were significantly different from each of the other groups ( p = 0.0001 vs de‐oligo sham tau, p = 0.0003 vs de‐oligo blast tau, and p < 0.0001 vs re‐oligo sham tau). N = 13 de‐oligo sham tau, 13 de‐oligo blast tau, 12 re‐oligo sham tau, 12 re‐oligo blast tau‐treated mice for this and the following panel. (C) Time spent freezing during initial pre‐foot shock exposure to fear conditioning chamber (baseline) and during reintroduction 24 h later for mice infused with de‐oligo or re‐oligo sham or blast tau. No significant differences in baseline freezing were observed among groups (ANOVA: F[346] = 0.3240, p = 0.8080). However, one‐way ANOVA for freezing at 24 h showed a significant difference among groups (F[346] = 6.617, p = 0.0008). Dunnett's post hoc comparisons at 24 h show that re‐oligomerized blast tau treated mice were significantly different from each of the other groups ( p = 0.0007 vs de‐oligo sham tau, p = 0.0081 vs de‐oligo blast tau, and p = 0.0020 vs re‐oligo sham tau). (D) Time course of Schaffer collateral field excitatory post‐synaptic potential (fEPSP) responses prior to and following delivery of theta‐burst stimulation (arrow) in wild‐type hippocampal slices treated with de‐oligo or re‐oligo sham or blast tau for 20 min (black bar). Two‐way RM ANOVA for fEPSP responses over the last 20 min of recording with treatment and time as factors shows a significant effect of treatment (F[362] = 5.371, p = 0.0024). Dunnett's multiple comparisons show that the re‐oligo blast tau‐treated group was significantly different from each of the other three groups ( p = 0.0030 vs de‐oligo sham tau, p = 0.0250 vs de‐oligo blast tau, and p = 0.0040 vs re‐oligo sham tau). N = 17 de‐oligo sham tau, 17 de‐oligo blast tau, 14 re‐oligo sham tau, 18 re‐oligo blast tau‐treated slices. All data presented as mean + SEM.
Article Snippet: As previously described, animals were placed in a transparent Plexiglas conditioning chamber (33 × 20 × 22 cm) (Noldus PhenoTyper).
Techniques: Sandwich ELISA, Isolation, One-tailed Test, Blocking Assay