title: Altered layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy.
abstract: OBJECTIVE
  Neuropathologic investigations frequently reveal the presence of architectural cortical dysplasia in patients with temporal lobe epilepsy (TLE), sometimes as an isolated finding but more commonly associated with hippocampal sclerosis (HS) and white matter abnormalities. The histologic pattern and the developmental origin of these alterations are not clear, and their diagnostic criteria are poorly defined. The aim of this study was to investigate the expression patterns of layer-specific genes in cortical specimens from patients with TLE presenting different subtypes of cortical malformations in order to elucidate the disorganization of the laminar architecture of such epileptogenic abnormalities and provide evidence to enable a more objective neuropathologic diagnosis.
  
  
  METHODS
  We analyzed the expression patterns of CUX2, RORBETA, ER81, NURR1, and CTGF genes, respectively specific markers of layers II-III, IV, V, VI, and VIb, in surgical samples by means of in situ hybridization and compared them with those observed in control cortices. The pathologic samples included typical architectural dysplasia (group 1); temporal lobe sclerosis, a variant of architectural dysplasia (group 2); and white matter heterotopic neuronal aggregates, namely small lentiform nodules (group 3). These abnormalities may have been associated or not with HS.
  
  
  RESULTS
  All of the genes had a laminar expression pattern in normal cortices, whereas groups 1 and 2 showed alterations mainly involving layers V and VI, and highlighted by the altered distribution of ER81- and NURR1-positive cells. The expression of ER81 and NURR1 genes was different among the groups, and atypical coexpression of NURR1 and CUX2 mRNA was detected in the neurons making up the small lentiform nodules.
  
  
  CONCLUSIONS
  These findings indicate that defects in cortical organization involving the deeper cortical neurons may be a common etiopathogenic mechanism in group 1 and 2 cortical dysplasia, whether isolated or associated with HS, and that developmental disorders may also be present in the white matter (group 3). They also provide evidence that the layer-specific genes can be usefully used to investigate the neuropathology of human cortical dysplasia.
authors: Clinical Epileptology and Experimental Neurophysiology Unit, IRCCS Foundation, C. Besta Neurological Institute, Milan, Italy.
authors: Laura
authors: L
authors: Rossini
authors: Ramona F
authors: RF
authors: Moroni
authors: Laura
authors: L
authors: Tassi
authors: Akiya
authors: A
authors: Watakabe
authors: Tetsuo
authors: T
authors: Yamamori
authors: Roberto
authors: R
authors: Spreafico
authors: Rita
authors: R
authors: Garbelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005095:Exoribonucleases / Q000096:biosynthesis; D015870:Gene Expression; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2 / Q000096:biosynthesis; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors
chemical_list: C080632:CUX1 protein, human; D018398:Homeodomain Proteins; C539882:NR4A2 protein, human; D009687:Nuclear Proteins; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C539740:RORB protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; C482201:ERI1 protein, human; D005095:Exoribonucleases