Intensity-dependent effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer’s disease

• Repetitive anodal tDCS can improve the spatial memory of Aβ1–40-lesioned rats.
• Repetitive anodal tDCS has intensity-dependent neuron-protective effects in AD rats.
• Anodal tDCS-induced effects are consequences of diverse neural pathway interactions.
• 10 sessions of 200 μA repetitive anodal tDCS, 20 min per session, is safe to rats.

Single-session anodal transcranial direct current stimulation (tDCS) can improve the learning-memory function of patients with Alzheimer’s disease (AD). After-effects of tDCS can be more significant if the stimulation is repeated regularly in a period. Here the behavioral and the histologic effects of the repetitive anodal tDCS on a rat model of AD were investigated. Sprague–Dawley rats were divided into 6 groups, the sham group, the β-amyloid (Aβ) group, the Aβ + 20 μA tDCS group, the Aβ + 60 μA tDCS group, the Aβ + 100 μA tDCS group and the Aβ + 200 μA tDCS group. Bilateral hippocampus of the rats in the Aβ group and the Aβ + tDCS groups were lesioned by Aβ1–40 to produce AD models. One day after drug injection, repetitive anodal tDCS (10 sessions in two weeks, 20 min per session) was applied to the frontal cortex of the rats in the tDCS groups, while sham stimulation was applied to the Aβ group and the sham group. The spatial learning and memory capability of the rats were tested by Morris water maze. Bielschowsky’s silver staining, Nissl’s staining, choline acetyltransferase (ChAT) and glial-fibrillary-acidic protein (GFAP) immunohistochemistry of the hippocampus were conducted for histologic analysis. Results show in the Morris water maze task, rats in the Aβ + 100 μA and the Aβ + 200 μA tDCS groups had shorter escape latency and larger number of crossings on the platform. Significant histologic differences were observed in the Aβ + 100 μA and the Aβ + 200 μA tDCS groups compared to the Aβ group. The behavioral and the histological experiments indicate that the proposed repetitive anodal tDCS treatment can protect spatial learning and memory dysfunction of Aβ1–40-lesioned AD rats.