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.