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Neurochemical Research

, Volume 41, Issue 11, pp 3020–3031 | Cite as

Abnormal Expression of FBXL20 in Refractory Epilepsy Patients and a Pilocarpine-Induced Rat Model

  • Pengfei Fu
  • YueTao Wen
  • Yan Xiong
  • Yanke Zhang
  • Haiyang Zhang
  • Yanfeng Xie
  • Quanhong ShiEmail author
Original Paper

Abstract

E3 ubiquitin ligases are important protein-modifying enzymes involved in the pathogenesis of a variety of neurodegenerative diseases. F-box and leucine-rich repeat protein 20 (FBXL20), an E3 ubiquitin ligase widely expressed in the central nervous system, plays an important role in the ubiquitin-dependent degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an important factor in the release of synaptic vesicles. FBXL20 has been associated with a variety of neurodegenerative diseases; thus, we hypothesized that FBXL20 is involved in the development of epilepsy. Herein, we used immunofluorescence staining, immunohistochemistry and western blotting to determine the expression pattern of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced epilepsy animal models. We also injected SD rats with lentivirus-vector mediated overexpression of FBXL20. The results showed that FBXL20 is expressed in the membrane and the cytoplasm of cortical neurons, and overexpression of FBXL20 decreased the onset level of spontaneous seizure, the frequency and duration of seizures. Additionally, FBXL20 protein level was decreased but RIM1 protein level was increased in the epileptic group compared with the LV-FBXL20 and LV-GFP group. These findings in humans were consistent with the results from a pilocarpine-induced animal model of chronic epilepsy. Thus, abnormal expression of FBXL20 might play an important role in the development of epilepsy.

Keywords

FBXL20 RIM1 Temporal lobe epilepsy Ubiquitination Synapse plasticity Synaptic vesicle 

Abbreviations

FBXL20

F-box and leucine-rich repeat protein 20

Rim1

Regulating synaptic membrane exocytosis 1

TLE

Temporal lobe epilepsy

CNS

Central nervous system

UPS

Ubiquitin-proteasome system

AEDs

Anti-epileptic drugs

EEG

Electroencephalography

F

Female

M

Male

VPA

Valproate

PB

Phenobarbital

CBZ

Carbamazepine

TPM

Topiramate

PHT

Phenytoin

LTG

Lamotrigine

OXC

Oxcarbazepine

LEV

Levetiracetam

TN

Temporal neocortex

l

Left

r

Right

NL

Neuronal necrosis

G

Gliosis

SD rats

Sprague-Dawley rats

IHC

Immunohistochemical

IF

Immunofluorescence

MRI

Magnetic resonance imaging

SE

Status epilepticus

RT-PCR

Real-time PCR

Notes

Acknowledgments

This work was supported by the Foundation of Chongqing Health Bureau (2013-1-005), and supported by the National key clinical specialty construction projects [2011-170]. We sincerely thank the support of Xuanwu Hospital and Tiantan Hospital of Capital Medical University, Xinqiao Hospital of the Third Military Medical University, and the First Affiliated Hospital of Chongqing Medical University, which provided the brain tissue samples. We also feel grateful for the patients and their families who participated in this study.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in the study involving human participants were in accordance with the ethical standards of the Chongqing Medical University and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Pengfei Fu
    • 1
  • YueTao Wen
    • 1
  • Yan Xiong
    • 2
  • Yanke Zhang
    • 2
  • Haiyang Zhang
    • 3
  • Yanfeng Xie
    • 1
  • Quanhong Shi
    • 1
    Email author
  1. 1.Department of NeurosurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Department of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  3. 3.Department of Pediatric Intensive Care UnitWest China Second University Hospital, Sichuan UniversityChengduChina

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