Rationale: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39 and CD73 are involved in the mechanism of DBS for epilepsy.
Methods: A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced epileptic rats), DBS (epileptic rats treated with DBS for eight weeks), and Sham (epileptic rats implanted with DBS electrodes without stimulation).
Video electroencephalogram monitoring, Morris water maze assays,
in vivo measurements of adenosine with fibred photometry, histochemistry and western blot were performed in the experiments.
Results: Electroencephalogram monitoring showed that DBS markedly attenuated spontaneous recurrent seizures (SRSs), and water maze assays demonstrated that DBS improved spatial learning and memory abilities in a rat model of epilepsy induced by pilocarpine. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. Expression of ENT1, CD39 and CD73 in Pilo group and Sham group increased compared with the control group, while the expression of ENT1, CD39 and CD73 in DBS group decreased compared to that of Pilo group and Sham group.
Conclusions: The findings indicate that
DBS retards progression of epilepsy and improves spatial memory in epileptic rats with concomitant decrease of ENT1, CD39 and CD73 expression. Adenosine modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.Funding: This project was supported by grants from the National Natural Science Foundation of China (81571275),
the National Key Research and Development Program of China (No. 2021YFC2401203)