Selective destruction of meningeal cells by 6-hydroxydopamine: a tool to study meningeal-neuroepithelial interaction in brain development.
The effects of 6-hydroxydopamine (6-OHDA) on meningeal cells were studied at different ages in conjunction with blockade of the neuronal uptake 1 for catecholamines using nomifensine (NMF) and of the extraneuronal uptake 2 using normetanephrine (NMN). Our results show that maximal numbers of meningeal cells over the cerebellum of the newborn rat are destroyed by a threshold dose of 6-OHDA of 25 micrograms. The morphological characteristics which mark the time course of degeneration of meningeal cells were used to assess the effects of 6-OHDA given in conjunction with either NMF or NMN to differentiate between neuronal (uptake 1) and extraneuronal (uptake 2) effects of 6-OHDA. Uptake of 6-OHDA into meningeal cells and their subsequent degeneration was prevented by pretreatment with NMN but not with NMF. This finding indicates that meningeal cells have uptake 2 capacity but no uptake 1 membrane pump and explains both their uptake of 6-OHDA and their extreme sensitivity to the toxic effects of this drug. Application of this pharmacological regimen using NMF and NMN in conjunction with 6-OHDA thus allows selective destruction of meningeal cells which may be used experimentally to study the contribution of meningeal cells to brain development.
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001345:Autoradiography; D001921:Brain / Q000254:growth & development*; D002450:Cell Communication; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D006892:Hydroxydopamines / Q000494:pharmacology*; D008578:Meninges / Q000166:cytology / Q000187:drug effects*; D008854:Microscopy, Electron; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D009647:Normetanephrine / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D013997:Time Factors
D006892:Hydroxydopamines; D009647:Normetanephrine; D009627:Nomifensine; D016627:Oxidopamine