Expression of the Nogo-A system in cortical lesions of pediatric patients with tuberous sclerosis complex and focal cortical dysplasia type IIb.
The reticulon protein Nogo-A is an important regulator of neurite growth, axonal plasticity, and cell migration in the central nervous system. Previous studies have shown markedly elevated levels of Nogo-A in human temporal lobe epilepsy. In the present study, we examined the expression pattern of the Nogo-A system in cortical lesions of pediatric patients with tuberous sclerosis complex and focal cortical dysplasia type IIb. These disorders are characterized by malformations of cortical development and are frequently associated with intractable epilepsy. We found that the messenger RNA and protein levels of the Nogo-A receptor (NgR) and the downstream targets of Nogo-A, LINGO-1, TROY, and RhoA but not P75 were upregulated in the cortices of patients compared with autopsy control samples. Immunohistochemical analyses indicated that Nogo-A and NgR were strongly expressed in misshapen cells, particularly dysmorphic neurons, balloon cells, and giant cells. TROY was diffusely expressed in the malformations of cortical development. Most of theNogo-A/NgR-positive misshapen cells were colabeled with neuronal rather than astrocytic markers. Taken together, our results suggestthat the activation of Nogo-A via the NgR/LINGO-1/TROY signal transduction pathways, but not NgR/LINGO-1/P75, may be involved in the development and/or seizure activity of cortical lesions in tuberous sclerosis complex and focal cortical dysplasia type IIb.
Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Si-Xun
SX
Yu
Song
S
Li
Hai-Feng
HF
Shu
Chun-Qing
CQ
Zhang
Shi-Yong
SY
Liu
Hui
H
Yang
D000704:Analysis of Variance; D001927:Brain Diseases / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000473:pathology*; D065703:Malformations of Cortical Development, Group I; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014402:Tuberous Sclerosis / Q000473:pathology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; C411850:TNFRSF19 protein, human; D020742:rhoA GTP-Binding Protein