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Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II and Tuberous Sclerosis Complex

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Abstract

Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC) are well-known causes of chronic refractory epilepsy in children. Canonical transient receptor potential channels (TRPCs) are non-selective cation channels that are commonly activated by phospholipase C (PLC) stimulation. Previous studies found that TRPC4 may participate in the process of epileptogenesis. This study aimed to examine the expression and distribution of TRPC4 in FCD II (n = 24) and TSC (n = 11) surgical specimens compared with that in age-matched autopsy control samples (n = 12). We found that the protein levels of TRPC4 and its upstream factor, PLC delta 1 (PLCD1), were elevated in FCD II and TSC samples compared to those of control samples. Immunohistochemistry assays revealed that TRPC4 staining was stronger in malformed cells, such as dysmorphic neurons, balloon cells and giant cells. Moderate-to-strong staining of the upstream factor PLCD1 was also identified in abnormal neurons. Moreover, double immunofluorescence staining revealed that TRPC4 was colocalised with glutamatergic and GABAergic neuron markers. Taken together, our results indicate that overexpression of TRPC4 protein may be involved in the epileptogenesis of FCD II and TSC.

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Acknowledgments

The investigators would like to thank the technicians Jin Peng, Qian Chen and Wen-Qiang Cai (Central Laboratory of Xinqiao Hospital, Third Military Medical University, Chongqing, China) for their excellent assistance with laser scanning confocal microscopy. This work was supported by the National Natural Science Foundation of China (No. 81471321, No. 81371424 and No. 81601142).

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Authors and Affiliations

  1. Epilepsy Research Center of PLA, Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 183 Xinqiao Main Street, Shapingba District, Chongqing, 400037, China

    Lu-Kang Wang, Chun-Qing Zhang, Chao Liang, Yu-Jia Wei, Jiong Yue, Shi-Yong Liu & Hui Yang

  2. Department of Neurosurgery, General Hospital of the People’s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083, China

    Xin Chen

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  1. Lu-Kang Wang
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  2. Xin Chen
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  3. Chun-Qing Zhang
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  4. Chao Liang
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  8. Hui Yang
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Correspondence to Hui Yang.

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Wang, LK., Chen, X., Zhang, CQ. et al. Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II and Tuberous Sclerosis Complex. J Mol Neurosci 62, 222–231 (2017). https://doi.org/10.1007/s12031-017-0923-z

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  • DOI: https://doi.org/10.1007/s12031-017-0923-z

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