EXPRESSION OF PURINE METABOLISM-RELATED ENZYMES BY MICROGLIAL CELLS IN THE DEVELOPING RAT-BRAIN

The nucleoside triphosphatase (NTPase), nucleoside diphosphatase (NDPa se), 5'-nucleotidase (5'-Nase), and purine nucleoside phosphorylase (P NPase) activity has been examined in the cerebral cortex, subcortical white matter, and hippocampus from embryonic day (E)16 to postnatal da y (P)18. Microglia display all four purine-related enzymatic activitie s, but the expression of these enzymatic activities differed depending on the distinct microglial typologies observed during brain developme nt. We have identified three main morphologic typologies during the pr ocess of microglial differentiation: ameboid microglia (parenchymatic precursors), primitive ramified microglia (intermediate forms), and re sting microglia (differentiated cells). Ameboid microglia, which were encountered from E16 to P12, displayed the four enzymatic activities. However, some ameboid microglial cells lacked 5'-Nase activity in gray matter, and some were PNPase-negative in both gray and white matter. Primitive ramified microglia were already observed in the embryonic pe riod but mostly distributed during the first 2 postnatal weeks. These cells expressed NTPase, NDPase, 5'-Nase, and PNPase. Similar to ameboi d microglia, we found primitive ramified microglia lacking the 5'-Nase and PNPase activities. Resting microglia, which were mostly distingui shable from the third postnatal week, expressed NTPase and NDPase, but they lacked or displayed very low levels of 5'-Nase activity, and onl y a subpopulation of resting microglia was PNPase-positive. Apart from cells of the microglial Lineage, GFAP-positive astrocytes and radial glia cells mere also labeled by the PNPase histochemistry. As shown by our results, the differentiation process from cell precursors into ma ture microglia is accompanied by changes in the expression of purine-r elated enzymes. We suggest that the enzymatic profile and levels of th e different purine-related enzymes may depend not only on the differen tiation stage but also on the nature of the cells. The use of purine-r elated histoenzymatic techniques as a microglial markers and the possi ble involvement of microglia in the control of extracellular purine le vels during development are also discussed. J. Comp. Neurol. 398:333-3 46, 1998. (C) 1998 Wiley-Liss, Inc.