Ex vivo direct current stimulation modulates synaptic plasticity under pathological condition with the implication of FKBP51-related signaling

Dysregulation of synaptic plasticity was associated with numerous neurological disorders, including ischemic long-term potentiation (iLTP). Direct current stimulation (DCS) changes neuronal plasticity by the weak direct current which induces depolarization and hyperpolarization of resting membrane potential with opposite direction of polarity. FK506-binding protein 51 (FKBP51) is considered an important molecular pathway that modulates synaptic plasticity in such disease models. The correlation of the regulatory effects in plasticity under pathological condition facilitated by DCS and FKBP51 remains to be investigated. To evaluate the neuronal plasticity effect after ex vivo anodal/cathodal DCS treatment, we applied ex vivo DCS treatment in oxygen-glucose deprivation (OGD)-induced iLTP model. First, upregulated synaptic responses were ameliorated by cathodal DCS (cDCS) and further enhanced by anodal DCS (aDCS) treatment after OGD induction in electrophysiological recording, corresponding with elevated GluN2B levels that alleviated after cDCS treatment in western blot assay. Increased levels of FKBP51 were suppressed by cDCS after OGD induction in western blot assay. Here, we also examine FKBP51-related signaling, including Akt and IKK phosphorylation. Raised phosphorylation levels of Akt were suppressed by both aDCS and cDCS treatment after OGD induction in western blot assay. Upregulated phosphorylation level of IKK was enhanced after DCS treatment after OGD induction. As mentioned above, our data showed that DCS treatment modulates synaptic plasticity with the involvement of FKBP51 and related signaling under pathological situation. More precisely, cDCS performed regulatory capabilities implicated in the modulation of FKBP51 level and Akt phosphorylation, while the properties of aDCS showed in Akt and IKK phosphorylation.