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

被引：0
作者：
Aronica E. [1 ,5 ]
Leenstra S. [2 ]
Jansen G.H. [3 ]
van Veelen C.W.M. [4 ]
Yankaya B. [1 ]
Troost D. [1 ]
机构：
[1] Department of Neuro Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam
[2] Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Amsterdam
[3] Department of (Neuro)Pathology, University Medical Center Utrecht, Utrecht
[4] Department of Neurosurgery, University Medical Center Utrecht, Utrecht
[5] Stichting Epilepsie Instellingen Nederland, Heemstede
来源：
Acta Neuropathologica | 2001年 / 101卷 / 4期
关键词：
Brain-derived neurotrophic factor; Epilepsy; Glioneuronal tumors; N-methyl-D-aspartic acid receptor; Tyrosine kinase B receptor;
D O I：
10.1007/s004010000296
中图分类号：
学科分类号：
摘要：
Recent evidence suggests that brain-derived neurotrophic factor (BDNF) and its tyrosine kinase B (TrkB) receptor, in addition to promoting neuronal survival and differentiation, modulates synaptic transmission by increasing N-methyl-D-aspartic acid receptor (NMDAR) activity. Overexpression of BDNF may, then, interfere with normal brain function, causing increased excitability. We have examined the immunohistochemical expression of BDNF, full-length TrkB receptor and the NMDAR subunit 1 and subunit 2A/B proteins (NMDAR1 and NMDAR2A/B) in glioneuronal tumors (gangliogliomas, GG, n=40; dysembryoplastic neuroepithelial tumors, DNT, n=15), from patients with chronic intractable epilepsy. The great majority of tumors studied were positive for all markers examined, supporting the high level of neurochemical differentiation of these lesions. BDNF and TrkB immunoreactivity (ir) was mainly observed in the neuronal component of the tumors. In GG, more than 90% of tumors contained 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 with 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 addition, since these neurons contain both NMDAR1 and NMDAR2A/B subunits, the BDNF-TrkB pathway may also contribute through a modulation of glutamatergic transmission to the intrinsic epileptogenicity of glioneuronal tumors.
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页码：383 / 392
页数：9
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共 79 条
  • [1] Aronica E., Dickson D.W., Kress Y., Morrison J.H., Zukin R.S., Non-plaque dystrophic dendrites in Alzheimer hippocampus: A new pathological structure revealed by glutamate receptor immunocytochemistry, Neuroscience, 82, pp. 979-991, (1998)
  • [2] Barde Y.A., Trophic factors and neuronal survival, Neuron, 2, pp. 1525-1534, (1989)
  • [3] Binder D.K., Routbort M.J., McNamara J.O., Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus, J Neurosci, 19, pp. 4616-4626, (1999)
  • [4] Binder D.K., Routbort M.J., Ryan T.E., Yancopoulos G.D., McNamara J.O., Selective inhibition of kindling development by intraventricular administration of TrkB receptor body, J Neurosci, 19, pp. 1424-1436, (1999)
  • [5] Blumcke I., Lobach M., Wolf H.K., Wiestler O.D., Evidence for developmental precursor lesions in epilepsy-associated glioneuronal tumors, Microsc Res Tech, 46, pp. 53-58, (1999)
  • [6] Bockers T.M., Zimmer M., Muller A., Bergmann M., Brose N., Kreutz M.R., Expression of the NMDAR1 receptor in selected human brain regions, Neuroreport, 5, pp. 965-969, (1994)
  • [7] Borrello M.G., Bongarzone I., Pierotti M.A., Luksch R., Gasparini M., Collini P., Pilotti S., Rizzetti M.G., Mondellini P., De Bernardi B., Trk and ret proto-oncogene expression in human neuroblastoma specimens: High frequency of trk expression in non-advanced stages, Int J Cancer, 54, pp. 540-545, (1993)
  • [8] Bramham C.R., Southard T., Sarvey J.M., Herkenham M., Brady L.S., Unilateral LTP triggers bilateral increases in hippocampal neurotrophin and trk receptor mRNA expression in behaving rats: Evidence for interhemispheric communication, J Comp Neurol, 368, pp. 371-382, (1996)
  • [9] Burger P.C., Scheithauer B.W., Tumors of the central nervous system, (1994)
  • [10] Ceccatelli S., Ernfors P., Villar M.J., Persson H., Hokfelt T., Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment, Proc Natl Acad Sci USA, 88, pp. 10352-10356, (1991)
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