Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy
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ORIGINAL ARTICLE
Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy De‑Feng Liu1 · Ying‑Chuan Chen1 · Guan‑Yu Zhu1 · Xiu Wang1 · Yin Jiang2 · Huan‑Guang Liu1,2 · Jian‑Guo Zhang1,2,3 Received: 26 August 2019 / Accepted: 6 November 2019 © Belgian Neurological Society 2019
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. Keywords Anterior nucleus of the thalamus (ANT) · Deep brain stimulation (DBS) · Epilepsy · Microarray · Kainic acid (KA) 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
* Huan‑Guang Liu [email protected]
Yin Jiang [email protected]
* Jian‑Guo Zhang [email protected]
1
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili, No.6, Dongcheng, Beijing 100050, China
2
Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Tiantan Xili, No.6, Dongcheng, Beijing 100050, China
3
Beijing Key Laboratory of Neurostimulation, Beijing 100050, China
De‑Feng Liu 18810663979
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