Dados do Trabalho

Título

WNT pathway alteration in displasic cortical tissue compared with no lesion adjacent tissue of pacientes with FCD and refractory epilepsy

Resumo

Background: Focal cortical dysplasia (FCD) is a malformation of the cortical development that cause medical refractory seizures and the only treatment may be surgical resection of the affected area of the brain. People affected by FCD may present seizures of variable severity since childhood. The physiopathology of the disease is not yet understood, however it is known that several genes alterations may play their role. The WNT/β-catenin pathway is associated with cell transformation and migration and for this reason may be crucial for understanding FCD’s aetiology. The aim of this study was to explore genes related to the WNT/β-catenin pathway in patients with FCD type II.
Methods: Dysplastic tissue and tissue adjacent to the primary dysplastic lesion of patients with FCD type II were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array containing 84 genes related to the WNT pathway.
Results: In patient 1, the analysis showed a difference in the expression of seven genes, demonstrating an increase in AXIN2, FRAT2, FZD9, KREMENI and PP2R1A genes and a reduction in CSNK1G3 and PPP2CA genes in dysplastic tissue. In patient 2, the analysis showed increased expression of CSNK1A1, FZD4 and PPP2CA genes, as well as reduced of CTNNBIP1 gene in dysplastic tissue.
Conclusion: Dysregulation in the expression of genes that control the receptors of the WNT pathway keeps it in an inactivated state. Therefore, a eventual manipulation of this pathway focusing on its activation may influence molecular manifestations underlying the epileptogenic status in injured brain tissue, which could act as a therapeutic alternative to FCD type II. The WNT/ β-catenin signaling pathway is crucial for the control of embryonic development, which takes place through the regulation of cell differentiation, migration and proliferation, and apoptosis process.

Palavras Chave

Cortical Focal Dysplasia, Epilepsy, WNT

Área

Epilepsia