Meningeal cells are involved in foliation, lamination, and neurogenesis of the cerebellum: Evidence from 6-hydroxydopamine-induced destruction of meningeal cells

Abstract

In the present paper we report on experiments conducted to find out if there is a positive correlation between the destruction of meningeal cells over the newborn rat cerebellum by 6-hydroxydopamine (6-OHDA) and the subsequent development of abnormalities in cerebellar fissuration, lamination, and granule cell number. (i) Both destruction of meningeal cells and quality and magnitude of 6-OHDA-induced cerebellar defects show the same threshold sensitivity without further dose responsiveness. (ii) Blockade of neuronal uptake 1 for catecholamines with nomifensine prevents neither destruction of meningeal cells nor the development of abnormalities in cerebellar structure after 6-OHDA treatment. (iii) Blockade of extraneuronal uptake 2 for catecholamines with normetanephrine prevents both destruction of meningeal cells and the development of typical cerebellar abnormalities after 6-OHDA treatment. All three parallel experiments suggest that there is a positive correlation between the destruction of meningeal cells and the development of abnormal cerebellar structure, indicating that meningeal cells are involved in these defective morphogenetic processes, i.e., fissuration, lamination, and cell proliferation in the external granular layer. The preferential localization of defects in cerebellar fissures indicates that, in analogy to the mesenchyme surrounding other epithelia with a branching morphogenesis, the role of meningeal cells could be the production of interstitial collagen which is necessary to stabilize the epithelial basal lamina in the fissures