Associated occurrence of p75 neurotrophin receptor expressing aldynoglia and microglia/macrophages in long term organotypic murine brain slice cultures

Abstract

Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann cell marker p75 neurotrophin receptor (NTR) have been shown to occur in some demyelinating diseases. However, the mechanisms determining the emergence and fate of such cells are largely unknown. This study aimed at the identification of such cells and potential triggering factors using an in vitro slice culture approach. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 days in vitro. Immunohistochemistry for the detection of p75NTR, CD107b, periaxin, growth associated protein (GAP)-43, and glial fibrillary acidic protein (GFAP) was performed. The results for p75NTR were substantiated by the use of in situ hybridization. Cultivation was associated with a progressively increasing spontaneous occurrence of bi- to multipolar p75NTR-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell like cells. Similar cells stained intensely positive for GAP-43, a marker for non-myelinating Schwann cells. The number of p75NTR positive glia did not correlate with GFAP expression, but showed a strong correlation with a remarkable spontaneous response of CD107b positive phagocytic microglia/macrophages. Moreover, aldynoglial p75NTR immunoreactivity negatively correlated to neuronal p75NTR expression, which was lost during culturing. The present results demonstrate that the cultivation of organotypic murine brain slices is accompanied by a spontaneous response of both microglia/macrophages and p75NTR positive cells, suggestive of Schwann cell like aldynoglia. The findings highlights the role of microglia/macrophages, which seem to be an important triggering factor, facilitating the occurrence of this unique type of macroglia.