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GPER1 Modulates Synaptic Plasticity During the Development of Temporal Lobe Epilepsy in Rats

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Abstract

G-protein coupled estrogen receptor 1 (GPER1) is a novel type of estrogen receptor. Several studies have shown that it has an anti-inflammatory action,which plays an important role in remyelination and cognitive ability adjustment. However, whether it is involved in the development of temporal lobe epilepsy (TLE) is still unknown. The present study established a TLE model by intraperitoneal injection of lithium chloride (3 mmol/kg) and pilocarpine (50 mg/kg) in rats to study the effect of GPER1 in the synaptic plasticity during the development of temporal lobe epilepsy. A microinjection cannula was implanted into the lateral ventricle region of rats via a stereotaxic instrument. G-1 is the specific GPER1 agonist and G15 is the specific GPER1 antagonist. The G1 or G15 and Dimethyl sulfoxide were injected into the rat brains in the intervention groups and control group, respectively. After G1 intervention, the learning and memory abilities and hippocampal neuron damage in epileptic rats were significantly improved, while G15 weakened the neuroprotective effect of GPER1. Meanwhile, G1 controlled the abnormal formation of hippocampal mossy fiber sprouting caused by seizures, and participated in the regulation of synaptic plasticity by reducing the expression of Synapsin I and increasing the expression of gephyrin. Inhibitory synapse gephyrin may play a significant role in synaptic plasticity.

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Abbreviations

GPER1:

G protein-coupled estrogen receptor 1

TLE:

Temporal lobe epilepsy

SE:

Status epilepticus

DMSO:

Dimethyl sulfoxide

MFS:

Mossy fiber sprouting

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Acknowledgements

The authors would like to acknowledge the Ningxia Medical University and Ningxia Hui Autonomous Region to support this work.

Funding

This work was supported by The 13.5 Major Scientific and Technological Projects of the Ningxia Hui Autonomous Region [Grant No. 2016BZ07], Ningxia Natural Science Foundation [Grant No. NZ17069], and Ningxia Medical University Advantage Discipline Group Project [Grant No. XY201902].

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Author notes

  1. Xian Zhang, Yang Yang and Li Guo have contributed to the work equally.

Authors and Affiliations

  1. Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750001, Ningxia, China

    Xian Zhang, Yang Yang, Jianguo Niu, Peng Wang, Yuanyuan Qiang, Kunmei Liu, Yujun Wen, Lianxiang Zhang & Feng Wang

  2. School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750001, Ningxia, China

    Yang Yang, Li Guo, Jianguo Niu, Yujun Wen & Lianxiang Zhang

  3. School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750001, Ningxia, China

    Jinyu Zhou

  4. Department of Neurosurgery, General Hospital of Ningxia Medical University, 804 Shengli Street, Yinchuan, 750001, Ningxia, China

    Feng Wang

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  1. Xian Zhang
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11064_2021_3336_MOESM1_ESM.tif

Fig. S. 1 The expression of GPER1 in hippocampus CA3 and DG regions in rats per group after intervention. (a) Immunohistochemistry in rats per group, (b) The expression of GPER1 in each group of rats; scale bar = 20 μm. Supplementary material 1 (TIF 20883.0 kb)

11064_2021_3336_MOESM2_ESM.tif

Fig. S. 2 Nissl staining was used to detect the damage and repair of CA3 and DG regions’ hippocampal neurons per group in rats; scale bar = 20 μm. Supplementary material 2 (TIF 23375.1 kb)

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Zhang, X., Yang, Y., Guo, L. et al. GPER1 Modulates Synaptic Plasticity During the Development of Temporal Lobe Epilepsy in Rats. Neurochem Res 46, 2019–2032 (2021). https://doi.org/10.1007/s11064-021-03336-8

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