Abnormal maturation of non-dysmorphic neurons in focal cortical dysplasia: immunohistochemical considerations.
OBJECTIVE
Dysmorphic neurons and balloon cells in focal cortical dysplasia (FCD) reportedly show immaturity and abnormal differentiation with neuronal and glial components. Although normal-looking neurons (NL-neurons) in FCD are major constituent elements, their biological characteristics have never been identified. The aim of this study was to investigate maturation of NL-neurons with the focus on neuronal developmental lineage.


METHODS
Eighteen FCD surgical specimens and controls were examined immunohistochemically using the antibodies for nestin, mammalian achaete-scute complex homolog 1 (Mash1), prospero-related homeobox 1 (Prox1), neuron-specific beta-III tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) of neuronal lineage, glutamic acid decarboxylase (GAD), calretinin (CR) and calbindin (CB) of interneuron markers, and glial fibrillary-acidic protein (GFAP) of glial cell marker. Additionally, we performed fluorescent-double staining with these markers, and semi-quantitative analysis.


RESULTS
NL-neurons in FCD had both mature and immature components, without interneuron components. NL-neurons in FCD showed abnormal maturation with the combined expression of MAP2 and Mash1/Prox1. Prox1-containing cell distribution in the deep layer was different from that of Mash1-containing cells in the superficial area. The MAP2-containing cell concentration decreased in the order of type I-A, I-B, II-A and II-B, but the Tuj1-containing cell concentration increased.


CONCLUSIONS
These findings may reflect differences in neuronal function and expression timing in developmental stages. From the standpoint of molecular expression, abnormal maturation of NL-neurons may initiate synaptic dysfunction, resulting in intractable seizures of FCD.
Hanai
Sae
S
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Kodaira, Japan.
Saito
Takashi
T
Nakagawa
Eiji
E
Arai
Asako
A
Otsuki
Taisuke
T
Sasaki
Masayuki
M
Goto
Yu-ichi
Y
Itoh
Masayuki
M
D000704:Analysis of Variance; D015415:Biomarkers; D002452:Cell Count; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000209:etiology / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007360:Intelligence; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure
D015415:Biomarkers; D009419:Nerve Tissue Proteins