Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease

摘要

Intracranial AC stimulation and the estimated current distribution. A–C Two small stainless steel screws were implanted in the skull at anterior-posterior (AP) = − 2 mm and medial-lateral (ML) = 4 (left and right) mm to the bregma. D, E The iACS was delivered through the screw electrodes on the dura. The mouse brain atlas was quoted from ref. [42]. F The three-dimensional (3D) brain model, based on a C57BL/6 mouse brain atlas built from MRI and Nissl histology, which consists of 39 different brain segments (in different colors, F1). F2–F4 The top (F2), front (F3), and side (F4) views of the 3D brain model with electrodes (white circles) on both hemispheres. F5 The dura layer of the 3D brain model. F6 The cerebral spinal fluid layer under the dura. F7 The white matter of the 3D brain model in color (other brain regions were shown in gray shade). F8 The gray matter of the 3D brain model in color (other brain regions were shown in gray shade). F9 The lateral ventricle of the 3D brain model in pink (other brain regions were shown in gray shade). F10 The hippocampus of the 3D brain model in orange (other brain regions were shown in gray shade). G Computer simulation was used to estimate the current densities (G1–G4, A/m2) and electric field strengths (G5–G8, V/m) in different brain regions, thus guide positioning of electrodes that would likely result in desirable and safe current and electric field distributions at sites of neurogenesis, including the subventricular zone (SVZ) and the hippocampus. The strongest currents and electric fields originate from the electrodes (circles in G) and flow into the brain with gradually decreasing density (G1, G3, G5, G7). The current of ~ 10 A/m2 (G3) and electric fields of ~ 10–50 V/m (G7) would reach the hippocampus. The strong current and electric field at the SVZ (~ 1–10 A/m2, ~ 10 V/m) are presumably due to interface of high conductivity, relatively low permittivity of CSF and less conductive, higher permittivity brain parenchyma (G2, G4, G6, G8)