Aberrant microtubule dynamics coupled with a reduction in Tau-microtubule interaction are at the core of neuronal injuries resulting in microtubule disruption and aggregates of abnormally phosphorylated Tau. These pathological Tau aggregates define tauopathies such as Alzheimer's disease (AD), as well as the pathological sequelae following traumatic brain injury (TBI), stroke and spinal cord injury (SCI). We hypothesized that differential applications of extremely low-frequency and low-intensity electromagnetic field (ELF-EMF) will change microtubule function. To examine our hypothesis, we pre-applied ELF-EMF to a neuroblastoma neuronal cell line later exposed to 4 h of zinc intoxication, modelling Tau-microtubule dissociation. ELF-EMF (40 Hz and 1 G
multiple exposure schedules) enhanced microtubule dynamics and increased Tau-microtubule interaction in the face of zinc toxicity. Complementing these preconditioning neuroprotective effects, concomitant 1 h treatment protocols comparing 3.9 or 40 Hz and 1 G exposure, indicated effects on Tau phosphorylation accentuated with 40 Hz and reduction in beta tubulin isotypes, depending on electromagnetic frequencies, most pronounced at 3.9 Hz. Our results discovered ELF-EMF modulation on the microtubule cytoskeleton essential for brain health.