Expression and cellular distribution of high- and low-affinity neurotrophin receptors in malformations of cortical development

An increasing number of observations suggests an important and complex role for both high- (tyrosine kinase receptor, trk) and low- (p75) affinity neurotrophin receptors (NTRs) during development in human brain. In the present study, the cell-specific distribution of NTRs was studied in different developmental lesions, including focal cortical dysplasia (FCD, n=15), ganglioglioma (GG, n=15) and dysembryoplastic neuroepithelial tumors, (DNT, n=10), from patients with medically intractable epilepsy. Lesional, perilesional, as well as normal brain regions were examined for the expression of trkA, trkB, trkC and p75(NTR) by immunocytochemistry. In normal postmortem human cortex, immunoreactivity (IR) for trk and p75(NTR) was mainly observed in pyramidal neurons, whereas no notable glial IR was found within the white matter. All three trk receptors were encountered in high levels in the neuronal component of the majority of FCD, GG and DNT specimens. Strong trkA, trkB and trkC IR was found in neurons of different size, including large dysplastic neurons and balloon cells in FCD cases. In contrast, p75(NTR) IR was observed in only a small number of neuronal cells, which also contain trk receptors. Glial cells with astrocytic morphology showed predominantly IR for trkA in FCD and GG specimens, whereas oligodendroglial-like cells in DNT showed predominently IR for trkB. P75(NTR) IR was observed in a population of cells of the microglial/macrophage lineage in both FCD and glioneuronal tumors. Taken together, our findings indicate that the neuronal and the glial components of malformations of cortical development express both high- and low-affinity NTRs. Further research is necessary to investigate how activation of these specific receptors could contribute to the development and the epileptogenicity of these developmental disorders.