Cerebral cortical dysplasia: giant neurons show potential for increased excitation and axonal plasticity.
Cerebral cortical dysplasia (CD) is a common cause of intractable childhood epilepsy. Five cases of CD were analyzed for GABA(A) receptor subunit beta (GABA(Abeta)), glutamate decarboxylase, AMPA receptor subunit 1 (GluR1) and subunit 2/3 (GluR2/3), and NMDA receptor 2 (NMDAR2) immunoreactivity. Antisera to the highly polysialylated neural cell adhesion molecule (PSA-NCAM) and human unc-33-like phosphoprotein 1 (hUlip 1) were used to identify neurons with 'developmentally immature' characteristics. Differences between CD and comparison tissue (n = 3) included: (1) prominent GABA(Abeta) immunoreactivity of the cytoplasm of dysmorphic neurons in the subcortical white matter and cortex in 1 CD case; (2) increased immunolabeling with anti-GluR1 and GluR2/3 antisera in dysmorphic neurons compared with more normal-appearing adjacent neurons and neurons from nondysplastic cortex; (3) varying numbers of cortical dysmorphic neurons stained for NMDAR2 in all 5 CD cases, in contrast to a complete lack of cellular immunoreactivity in 2/3 of the cases of nondysplastic cortex; (4) PSA-NCAM and hUlip 1 expression (usually observed only in populations of neurons that undergo axonal growth) was observed in CD tissue, but not in normal brain tissue. In summary, dysmorphic neurons in cases of CD have increased immunoreactivity for several excitatory neurotransmitter receptor subunits, show variable immunoreactivity for GABA(Abeta) and show expression of several proteins that are normally expressed only in immature neurons or those with the potential for synaptic plasticity.
Kerfoot
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Department of Pathology and Laboratory Medicine (Neuropathology), UCLA Medical Center, Los Angeles, CA 90095-1732, USA. ckerfoot@ucla.edu
Vinters
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HV
Mathern
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GW
D001369:Axons / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015726:Giant Cells / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009124:Muscle Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism
C102926:DPYSL3 protein, human; D007106:Immune Sera; D009124:Muscle Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D010750:Phosphoproteins; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule