J Korean Med Sci.  2004 Jun;19(3):419-425. 10.3346/jkms.2004.19.3.419.

Upregulation of Glutamate Receptors in Rat Cerebral Cortex with Neuronal Migration Disorders

• Lee MC
• Shim JJ
• Kim JH
• Kim MK
• Woo YJ
• Chung WK
• Suh JJ
• Nam SC
• Lee JS
• Kim YS
• Kim JH
• Kim HI

• KMID: 1786822
• DOI: http://doi.org/10.3346/jkms.2004.19.3.419

Abstract

Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immunohistochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs.

Keyword

Cerebral Cortex, Cortical Dysplasia; Epilepsy; Neuron; Neuronal Migration Disorder (NMD); Radiation; Receptors, Glutamate

MeSH Terms

Animals
Cell Movement
Cerebral Cortex/*metabolism
Electroencephalography
Glutamic Acid/metabolism
Immunohistochemistry
Kainic Acid/pharmacology
Neurons/*metabolism/pathology
Rats
Rats, Wistar
Receptors, Glutamate/metabolism
Receptors, N-Methyl-D-Aspartate/*biosynthesis
Support, Non-U.S. Gov't
Time Factors
*Up-Regulation

Figure

• 

  Fig. 1 Pathophysiologic features in a rat with neuronal migration disorder (NMD). EEG from an NMD rat with kainic acid provocation (1 mg/kg, ip) shows abnormal rhythmic spikes initially developed from the cortex, and then from the hippocampus (A). Comparing with control cortex (AL-116), coronal section of the irradiation-induced NMD brain (AL-119) disclose microcephaly, markedly thinned neocortex, agenesis of corpus callosum, and blurring of the gray and white matter junction (B). Histopathologic features of NMD reveal increased immunoreactivities for neurofilament protein (NF-M/H) in a focal area of the gray matter (C, ×10), and abnormally oriented cytomegalic neurons (D, ×120).

• 

  Fig. 2 Immunohistochemistry for glutamate receptor subunit proteins in the control and NMD cortex. Control cortex shows diffuse and moderate expression of NR1 in the neurons throughout the gray matter (A, ×40), and discrete expression of GluR3 in some large pyramidal neurons of the deep gray matter (B, ×40). NMD cortex discloses significantly increased expression of NR1 (C, ×100), NR2A/B (D, ×100), and GluR2 (E, ×100) in subpial heterotopic neurons and cytomegalic neurons.

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