Neuronal Cytoskeletal Abnormalities and Neurotrophin Receptor Immunoreactivity in Severe Cerebral Cortical Dysplasia

ABSTRACT

BACKGROUND: Cerebral cortical dysplasia (CD) is one of the important causes of intractable epilepsies and characterized histologically by disorganized cortical lamination and cytomegalic dysplastic neurons. Although various cytoskeletal abnormalities have been found in dysplastic neurons of CD, the pathogenetic role of dysplastic neurons has rarely been investigated. METHODS: In this study, immunohistochemical analysis was performed using antibodies against non-phosphorylated high- or medium-molecular weight neurofilament protein and microtubule-associated protein 2 (MAP-2) in surgical specimens of CD. In order to know the possible relationship of dysplastic neurons with cytoskeletal abnormalities and various neurotrophin receptors, NGFR p75, trkA, trkB, and trkC immunoreactivities were also analyzed. RESULTS: Dysplastic neurons showed strong immunoreactivities for non-phosphorylated high- or medium-molecular weight neurofilament protein and MAP-2, which might reflect abnormal outgrowth and altered plasticity of the dysplastic neurons. TrkB and trkC were strongly expressed in dysplastic neurons and NGFR p75 was also strongly expressed in some dysplastic neurons. CONCLUSIONS: Since it has been known that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have effects on the differentiation of neuronal precursor cells from the cortex and on dendritic and axonal arborization, increased expression of trkB and trkC may play a role in cytoskeletal abnormalities and altered synaptic transmission in dysplastic neurons.