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Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy

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Abstract

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) has been shown to be effective and safe in the long-term treatment of refractory epilepsy. However, the mechanisms by which ANT-DBS controls epilepsy at the gene expression level (e.g., which regulatory mechanisms are altered) is not well understood. Nine rats were randomly assigned to the control group, the kainic acid (KA) group, and the DBS group. Temporal lobe epilepsy in rats was induced by a stereotaxic KA injection (KA group). The DBS group received the KA injection followed by treatment with ANT-DBS. Video-electroencephalogram (EEG) was used to monitor seizures. Total RNA samples were isolated from the hippocampus of three groups. Microarray was used to detect differentially regulated mRNAs. GO and pathway analysis were performed to analyze the functional categories and affected pathways. qPCR was used to prove the reliability of the microarray results. The differentially expressed genes the KA group and the DBS group, relative to the control group, were screened and a total of 2910 genes were identified. These genes were involved in functional categories such as ion channel activity (P = 5.01 × 10−8), gated channel activity (P = 1.42 × 10−7), lipid binding (P = 4.97 × 10−5), and hydrolase activity (P = 5.02 × 10−5) and pathways such as calcium signaling pathway (P = 2.09 × 10−8), glutamatergic synapse (P = 4.09 × 10−8) and NOD-like receptor signaling pathway (P = 2.70 × 10−6). Differentially expressed mRNAs might play a role in the pathogenesis of temporal lobe epilepsy. Calcium signaling pathways, synaptic glutamate, and NOD-like receptor signaling pathway play a central role in normal-epilepsy-ANT-DBS treatment series. ANT-DBS achieves its antiepileptic effects by modulating target genes involved in a variety of functions and pathways.

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Abbreviations

ANT:

Anterior nucleus of the thalamus

DBS:

Deep brain stimulation

KA:

Kainic acid

SD:

Standard deviation

MTLE:

Mesial temporal lobe epilepsy

qPCR:

Quantitative real time PCR

TS:

Total seizures

PS:

Partial seizures

GS:

Generalized seizures

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Acknowledgements

This study was supported by the National Natural Science Funds for Distinguished. Young Scholars (No. 81501118; 81501186) and Beijing Municipal Administration of Hospitals’Ascent Plan (DFL20150503). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili, No.6, Dongcheng, Beijing, 100050, China

    De-Feng Liu, Ying-Chuan Chen, Guan-Yu Zhu, Xiu Wang, Huan-Guang Liu & Jian-Guo Zhang

  2. Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Tiantan Xili, No.6, Dongcheng, Beijing, 100050, China

    Yin Jiang, Huan-Guang Liu & Jian-Guo Zhang

  3. Beijing Key Laboratory of Neurostimulation, Beijing, 100050, China

    Jian-Guo Zhang

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  1. De-Feng Liu
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Correspondence to Huan-Guang Liu or Jian-Guo Zhang.

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Ethical approval

This study was approved by the Beijing Neurosurgical Institute ethics committee. All animal experiments were performed in accordance with the Guidance for Animal Experimentation of the Capital Medical University and Beijing Guidelines for the care and use of laboratory animals. All efforts have been made to minimize animal suffering during the procedures.

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Liu, DF., Chen, YC., Zhu, GY. et al. Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy. Acta Neurol Belg 120, 1361–1370 (2020). https://doi.org/10.1007/s13760-019-01240-1

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  • DOI: https://doi.org/10.1007/s13760-019-01240-1

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