title: Similar PDK1-AKT-mTOR pathway activation in balloon cells and dysmorphic neurons of type II focal cortical dysplasia with refractory epilepsy.
abstract: Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis of these cells may be critical to the histological findings in type II FCD. Recent work has shown enhanced activation of the mTOR cascade in both balloon cells and dysmorphic neurons, suggesting a common pathogenesis for these two neuropathological hallmarks. A direct comparative analysis of balloon cells and dysmorphic neurons might identify a molecular link between balloon cells and dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation differentiates balloon cells from dysmorphic neurons. We used immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6 kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or moderate staining for components of the PDK1-AKT-mTOR signaling pathway was observed in both balloon cells and dysmorphic neurons. However, only a few pyramidal neurons displayed weak staining in control group (perilesional neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT (Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in dysmorphic neurons. Our data support the previously suggested pathogenic relationship between balloon cells and dysmorphic neurons concerning activation of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway between balloon cells and dysmorphic neurons may result from cell-specific gene expression.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address: lyx99070@163.com.
authors.forename: Yuan-xiang
authors.initials: YX
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Fujian Provincial Hospital, Fuzhou 350005, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
authors.forename: De-zhi
authors.initials: DZ
authors.lastname: Kang
authors.affiliation: Department of Ultrasonic Image, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
authors.forename: Xin-xiu
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Pathology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
authors.forename: Xing-fu
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
authors.forename: Shu-fa
authors.initials: SF
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
authors.forename: Liang-hong
authors.initials: LH
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
authors.forename: Zhang-ya
authors.initials: ZY
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004827:Epilepsy / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D065703:Malformations of Cortical Development, Group I / Q000150:complications / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases
keywords: Balloon cells; Dysmorphic neurons; Focal cortical dysplasia; Intractable epilepsy; mTOR