title: [Expression of autophagy-related proteins in malformations of cortical development].
abstract: OBJECTIVE
  To study the expression of autophagy-related proteins (Beclin-1, LC3 and p62) in brain tissue with malformations of cortical development and related molecular pathogenesis.
  
  
  METHODS
  The brain tissue of 18 cases with epileptogenic foci resection, including 6 cases of tuberous sclerosis complex (TSC), 6 cases of focal cortical dysplasia type IIb (FCD IIb) and 6 cases of focal cortical dysplasia type I (FCD I), were retrieved. Immunohistochemical study for Beclin-1, LC3 and p62 proteins was performed. The degree of positivity for Beclin-1 and LC3 proteins was compared. Western blot was used to quantitatively analyze the LC3 protein in focal lesion of each disease groups.
  
  
  RESULTS
  Immunohistochemical study showed that the three proteins were mainly expressed in the dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb. The positivity was more intense in the dysmorphic neurons than the other cell types. Immunostaining for Beclin-1 showed granular or diffuse cytoplasmic positivity, in addition to the strong expression in axons. On the other hand, LC3 showed diffuse or perinuclear cytoplasmic expression. The staining for p62 was mainly cytoplasmic or perinuclear and sometimes nuclear. In FCD type I, only individual cells showed positive expression for the three proteins. The number of Beclin-1 and LC3-positive cells was larger in TSC group, followed by FCD IIb group and FCD I group.And there were significant differences between TSC group and FCD I group, as well as FCD IIb group and FCD I group (P<0.05). Quantitative expression of LC3 protein by Western blot showed smaller amount in TSC group, followed by FCD IIb group and FCD I group.
  
  
  CONCLUSIONS
  The dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb show abnormality in autophagy, resulting in intracytoplasmic protein accumulation. There are differences in molecular pathogenesis in these cell types.
authors.affiliation: Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; E-mail: yueshanpiao@126.com.
authors.forename: Yueshan
authors.initials: Y
authors.lastname: Piao
authors.affiliation: Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yongjuan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Dehong
authors.initials: D
authors.lastname: Lu
mesh_terms: D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D000071186:Beclin-1 / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism; D005260:Female; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D054220:Malformations of Cortical Development / Q000378:metabolism*; D065703:Malformations of Cortical Development, Group I / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000378:metabolism
chemical_list: D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins