Deep brain stimulation of the anterior nuclei of the thalamus relieves basal ganglia dysfunction in monkeys with temporal lobe epilepsy

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Abstract

Aims: Deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) is effective in temporal lobe epilepsy (TLE). Previous studies have shown that the basal ganglia are involved in seizure propagation in TLE, but the effects of ANT-DBS on the basal ganglia have not been clarified. Methods: ANT-DBS was applied to monkeys with kainic acid–induced TLE using a robot-assisted system. Behavior was monitored continuously. Immunofluorescence analysis and Western blotting were used to estimate protein expression levels in the basal ganglia and the effects of ANT stimulation. Results: The seizure frequency decreased after ANT-DBS. D1 and D2 receptor levels in the putamen and caudate were significantly higher in the ANT-DBS group than in the epilepsy (EP) model. Neuronal loss and apoptosis were less severe in the ANT-DBS group. Glutamate receptor 1 (GluR1) in the nucleus accumbens (NAc) shell and globus pallidus internus (GPi) increased in the EP group but decreased after ANT-DBS. γ-Aminobutyric acid receptor A (GABAA-R) decreased and glutamate decarboxylase 67 (GAD67) increased in the GPi of the EP group, whereas the reverse tendencies were observed after ANT-DBS. Conclusion: ANT-DBS exerts neuroprotective effects on the caudate and putamen, enhances D1 and D2 receptor expression, and downregulates GPi overactivation, which enhanced the antiepileptic function of the basal ganglia.

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Du, T., Chen, Y., Shi, L., Liu, D., Liu, Y., Yuan, T., … Zhang, J. (2021). Deep brain stimulation of the anterior nuclei of the thalamus relieves basal ganglia dysfunction in monkeys with temporal lobe epilepsy. CNS Neuroscience and Therapeutics, 27(3), 341–351. https://doi.org/10.1111/cns.13462

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