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The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?

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Abstract

Temporal lobe epilepsy is one of the most common clinical neurological disorders. One of the major pathological findings in temporal lobe epilepsy is hippocampal sclerosis, characterized by massive neuronal loss and severe gliosis. The epileptogenesis process of temporal lobe epilepsy usually starts with initial precipitating insults, followed by neurodegeneration, abnormal hippocampus circuitry reorganization, and the formation of hypersynchronicity. Experimental and clinical evidence strongly suggests that dysfunctional neurogenesis is involved in the epileptogenesis. Recent data demonstrate that neurogenesis is induced by acute seizures or precipitating insults, whereas the capacity of neuronal recruitment and proliferation substantially decreases in the chronic phase of epilepsy. Participation of the Wnt/β-catenin signaling pathway in neurogenesis reveals its importance in epileptogenesis; its dysfunction contributes to the structural and functional abnormality of temporal lobe epilepsy, while rescuing this pathway exerts neuroprotective effects. Here, we summarize data supporting the involvement of Wnt/β-catenin signaling in the epileptogenesis of temporal lobe epilepsy. We also propose that the Wnt/β-catenin signaling pathway may serve as a promising therapeutic target for temporal lobe epilepsy treatment.

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Abbreviations

AEDs:

Anti-epileptic drugs

APC:

Adematous polyposis coli

Ara-C:

Cytosine-β-d-arabinofuranoside

Axin:

Axis inhibition protein

BDNF:

Brain-derived neurotrophic factor

Cer:

Cerberus

CNS:

Central nervous system

COX2:

Cyclooxygenase 2

DCX:

Doublecortin

DG:

Dentate gyrus

Dkk:

Dickkopf

Dvl:

Disheveld

E2:

Estrogen

ECS:

Electroconvulsive seizures

FGF-2:

Fibroblast growth factor-2

Fz:

Frizzled

GABA:

γ-Aminobutyric acid

GSK-3β:

Glycogen synthase kinase-3β

HDAC:

Histone deacetylase

HS:

Hippocampal sclerosis

KA:

Kainic acid

LiCl:

Lithium chloride

LRP5/6:

Low-density lipoprotein receptor-related protein 5 or 6

MAP1B:

Microtubule-associated protein 1B

NCAM:

Neural cell adhesion molecule

NGF:

Nerve grow factor

NPCs:

Neural progenitor cells

NPY:

Neuropeptide Y

NSCs:

Neural stem cells

PSA:

Polysialic acid

SE:

Status epilepticus

sFRP:

Secreted frizzled-related protein

Shh:

Sonic hedgehog

SVZ:

Subventricular zone

SZG:

Subgranular zone

TLE:

Temporal lobe epilepsy

VEGF:

Vascular endothelial growth factor

VPA:

Valproic acid

WIF1:

Wnt inhibitory factor 1

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  1. Department of Neurology, West China Hospital, Sichuan University, 37th Guoxue Allay, Chengdu, 610041, People’s Republic of China

    Cheng Huang, Dong Zhou & Jin-Mei Li

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17 South Renmin Road Section 3, Chengdu, 610041, People’s Republic of China

    Cheng Huang & Xiang-Hui Fu

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Huang, C., Fu, XH., Zhou, D. et al. The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?. Neurochem Res 40, 1319–1332 (2015). https://doi.org/10.1007/s11064-015-1614-1

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