Expression of brain-derived neurotrophic factor and tyrosine kinase B receptor proteins in glioneuronal tumors from patients with intractable epilepsy: colocalization with N-methyl-D-aspartic acid receptor

Recent evidence suggests that brain-derived neurotrophic factor (BDNF) and its tyrosine kinase B (TrkB) receptor, in addition to promoting neuronal su rvival and differentiation, modulates synaptic transmission by increasing N -methyl-D-aspartic acid receptor (NMDAR) activity. Overexpression of BDNF m ay, then, interfere with normal brain function, causing increased excitabil ity. We have examined the immunohistochemical expression of BDNF, full-leng th TrkB receptor and the NMDAR subunit 1 and subunit 2A/B proteins (NMDAR1 and NMDAR2A/B) in glioneuronal tumors (gangliogliomas, GG, n=40; dysembryop lastic neuroepithelial tumors, DNT, n=15), from patients with chronic intra ctable epilepsy. The great majority of tumors studied were positive for all markers examined, supporting the high level of neurochemical differentiati on of these lesions. BDNF and TrkB immunoreactivity (ir) was mainly observe d in the neuronal component of the tumors. In GG, more than 90% of tumors c ontained very intense BDNF-ir ganglion cells. Double labeling confirmed the presence of BDNF-ir and TrkB-ir in neurons which contained NMDAR1. NMDAR2A /B intensely labeled abnormal neurons in both GG and DNT and co-localized w ith NMDAR1. The presence of BDNF and its receptor in the neuronal component of GG and DNT may suggest a role for this neurotrophin in the development of these lesions, preventing the death of abnormal neuronal cells. In addit ion, since these neurons contain both NMDAR1 and NMDAR2A/B subunits, the BD NF-TrkB pathway may also contribute through a modulation of glutamatergic t ransmission to the intrinsic epileptogenicity of glioneuronal tumors.