a, Percent of unmyelinated axons (n=3; 4 images scored from each biological replicate). p=0.005. b, G-ratio (r/R) of all axons (4EP-, 56; 4EP+, 70 axons)(n=4; 4 images scored from each biological replicate). p=0.0001. c, Width of myelin; (4EP-, 56; 4EP+, 70 axons) (n=4; 4 images scored from each biological replicate). p=0.003. d, Representative electron tomography images. Several myelinated and unmyelinated axons marked by blue and orange arrows, respectively. e, Fractional anisotropy (FA) measured by diffusion tensor imaging (DTI) (n=4). p=0.04. f, Elevated plus maze: time spent in the terminus (outer one-third) of the open arms (4EP+ n=21; 4EP- n=24). p=0.003. g, Open field test (4EP+ n=21; 4EP- n=24). p=0.002. h, Number of marbles buried (4EP+ n=24; 4EP- n=23). p=0.02. i, Maturity quotient of oligodendrocytes in the PVT of 4EP- and 4EP+ mice ±clemastine fumarate (Cumulative totals used from individual mice: 4EP- control=7, treated=10; 4EP+ control=6, treated=6)(Cont 4EP-vs 4EP+ p=0.03; 4EP+Cont vs Treatment p=0.01). j, Representative images of brain sections from mice ±clemastine fumarate, stained for CC1 (green) and NG2 (red). k-m, Behavioral tests of mice (independent of cohorts used previously) ±clemastine fumarate. k, EPM (4EP- control n=13, treated n=13; 4EP+ control n=12, treated n=14)(4EP+Cont vs Treatment p=0.05). l, Open field test (4EP- control =15, treated n=17; 4EP+ control n=17, treated n=17) p=0.04. m, Number of marbles buried(4EP- control =15, treated n=17; 4EP+ control n=17, treated n=17)(Cont 4EP-vs 4EP+ p=0.009; 4EP+Cont vs Treatment p=0.03). Abbreviations: FA, fractional anisotropy; NG2; neural/glial antigen 2; CC1, adenomatous polyposis coli. Biologically independent mice from multiple randomized litters examined over two respective experiments used for all experiments. Data represent mean ± SEM analyzed by two-tailed Welch’s t-test (a-h) or two-way ANOVA with Dunnett multiple comparison to the 4EP+control group (i-m). *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001.