Fig. 1

LFS-induced and age-dependent oligomerization of tau in wild-type mouse hippocampus. a Experimental schedules used in this study. In the LFS group, 1800 electrical pulses at 1 Hz were applied to one side of the hippocampus (Schaffer’s collateral area in the CA1) in anesthetized mice before hippocampus sampling. In the sham-control group, each mouse received the same operation (anesthetization, electrode penetration, test stimulation for determination of the insertion area) as the LFS group but did not receive LFS. b, c Typical western blot analysis of sarkosyl-soluble (SS) and sarkosyl-insoluble (SI) fractions obtained from a contralateral (C) and ipsilateral (I) hippocampus from an aged LFS mouse. Blots were analyzed for total tau expression with antibody A0024 (b) and Tau5 (c) and for phosphorylated tau with anti-PS396-tau c. d Graph showing the mean normalized tau levels (detected by using A0024) in SI fractions at ipsilaterally stimulated (I) and control (unstimulated) contralateral (C) hippocampi in the sham and LFS groups of adult and aged animals (adult sham, n = 4; adult LFS, n = 5; aged sham, n = 5; aged LFS, n = 8). ** p < 0.01, unpaired t-test; #p < 0.05, one-sample t-test against a theoretical value of ‘1’. e Typical electron microscopy images showing the morphology of tau aggregates from the SI fraction from hippocampi of aged LFS mice. Each black dot is an immunogold particle attached to the indicated tau antibodies. Bar: 20 nm. f LFS induced increases in oligomeric tau, which was immunoprecipitated (IP) by the T22 antibody from the ipsilateral side (I), but not the contralateral side (C), although such side-specific increases in precipitated tau were not detected in the total tau level of P2 fractions (input). A0024 was used for western blot analysis. These tendencies were confirmed in three independent experiments