Details

Autor(en) / Beteiligte

• Boer, K
• Troost, D
• Timmermans, W
• Gorter, J.A
• Spliet, W.G.M
• Nellist, M
• Jansen, F
• Aronica, E

Titel

Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex

Ist Teil von

• Neuroscience, 2008-09, Vol.156 (1), p.203-215

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with cortical malformations (cortical tubers) and the development of glial tumors (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate receptor (mGluR) subtypes is developmentally regulated and several studies suggest an involvement of mGluR-mediated glutamate signaling in the regulation of proliferation and survival of neural stem-progenitor cells, as well as in the control of tumor growth. In the present study, we have investigated the expression and cell-specific distribution of group I (mGluR1, mGluR5), group II (mGluR2/3) and group III (mGluR4 and mGluR8) mGluR subtypes in human TSC specimens of both cortical tubers and SGCTs, using immunocytochemistry. Strong group I mGluR immunoreactivity (IR) was observed in the large majority of TSC specimens in dysplastic neurons and in giant cells within cortical tubers, as well as in tumor cells within SGCTs. In particular mGluR5 appeared to be most frequently expressed, whereas mGluR1α was detected in a subpopulation of neurons and giant cells. Cells expressing mGluR1α and mGluR5, demonstrate IR for phospho-S6 ribosomal protein (PS6), which is a marker of the mammalian target of rapamycin (mTOR) pathway activation. Group II and particularly group III mGluR IR was less frequently observed than group I mGluRs in dysplastic neurons and giant cells of tubers and tumor cells of SGCTs. Reactive astrocytes were mainly stained with mGluR5 and mGluR2/3. These findings expand our knowledge concerning the cellular phenotype in cortical tubers and in SGCTs and highlight the role of group I mGluRs as important mediators of glutamate signaling in TSC brain lesions. Individual mGluR subtypes may represent potential pharmacological targets for the treatment of the neurological manifestations associated with TSC brain lesions.