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: Tau from shockwave‐exposed but not sham‐exposed mice impairs cognition and synaptic plasticity. (A) Number of errors committed during testing on a 2‐day radial arm water maze task for wild‐type (WT) mice infused with vehicle, tau isolated from sham‐exposed mice (sham tau), tau isolated from shockwave‐exposed mice (blast tau), or mock purified material from shockwave exposed tau KO mice (tau KO) shows that blast tau‐treated mice commit significantly more errors than each of the other groups. 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[352] = 16.41, p < 0.0001). Dunnett's post hoc comparisons show that blast tau‐treated mice were significantly different from vehicle‐treated mice ( p = 0.0005), sham tau‐treated mice ( p < 0.0001), and mock purified material from shockwave‐exposed tau KO mice ( p < 0.0001). N = 10 vehicle, 16 sham tau, 16 blast tau, 14 tau KO treated mice for this and the following panel. (B) Time spent freezing during initial pre‐foot shock exposure to fear conditioning chamber (baseline) and during reintroduction 24 h later for mice infused with vehicle, sham tau, blast tau, or mock purified material from shockwave exposed tau KO mice. No significant differences in baseline freezing were observed among groups (ANOVA: F[352] = 0.1207, p = 0.9475). However, one‐way ANOVA for freezing at 24 h showed a significant difference among groups (F[352] = 16.90, p < 0.0001). Dunnett's multiple comparisons show that the blast tau‐treated group was significantly different from each of the other three groups ( p < 0.0001). (C) Time course of Schaffer collateral field excitatory post‐synaptic potential (fEPSP) responses prior to and following delivery of theta‐burst stimulation (arrow) in WT hippocampal slices treated with vehicle, sham tau, blast tau, or mock purified material from shockwave‐exposed tau KO mice 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[354] = 8.796, p < 0.0001). Dunnett's multiple comparisons show that the blast tau‐treated group was significantly different from each of the other three groups (vs vehicle: p = 0.0039; vs sham tau: p < 0.0001; vs tau KO: p = 0.0064). N = 9 vehicle, 20 sham tau, 20 blast tau, 9 tau KO‐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: Isolation, Purification, Blocking Assay

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