Ultrastructural localization of CD38 immunoreactivity in rat brain

Abstract

The subcellular localization of CD38 in the rat cerebral and cerebellar cortices was studied using immunoelectron microscopy. In the cerebral cortex, immunoreactivity was present in a subset of pyramidal neurons, and was distributed predominantly in the perikarya and dendrites. It was found in association with rough endoplasmic reticulum, ribosomes, small vesicles, mitochondria and the plasma membrane including the postsynaptic densities. In the cerebellum, labeling was observed in several types of neuron such as granule, Golgi, basket and Purkinje cells. In contrast to the cerebrum, immunoreactivity was accentuated in the perikarya or axon terminals, and the synaptic vesicles represented another organelle that was immunopositive for CD38. In both of these CNS regions, the nuclear envelope, particularly the outer membrane, showed constant labeling. Diffuse immunoreactivity was also present in the astrocytes from the perikarya to the processes including the perivascular glia limitans. Oligodendrocytes and microglia were immunonegative for CD38. The pattern of distribution of CD38 in the CNS is suggestive of multiple roles for this molecule at various functional sites in both neurons and astrocytes. © 1997 Elsevier Science B.V.

Introduction

CD38 is a type II transmembrane glycoprotein 6, 20, and was originally identified as a human lymphocytic surface antigen [17]. In addition to several biological activities such as cell adhesion, cell activation and cytokine induction [11], this protein has a bifunctional role catalyzing both ADP-ribosyl cyclase and cyclic ADP-ribose (cADPR) hydrolase reactions 4, 18, 19, 21, and contributes to the formation and hydrolysis of cADPR. Recent studies have provided evidence that cADPR is a second messenger which mobilizes intracellular Ca²⁺ by coupling with the ryanodine receptor 2, 12, and that it controls the physiological activities of cells including neurons of the central nervous system (CNS) [1]. Thus, CD38 may also play an important role in intracellular Ca²⁺ signaling. Although the expression of CD38 mRNA has been reported to occur in brain tissue 7, 9as well as in other organs 8, 10, 20, little is known about its cellular distribution and intracellular functional sites in the CNS. Previously, we reported the neuronal localization of CD38 in the human brain [13]. In the study described here, we investigated the subcellular localization of CD38 in the rat brain using immunoelectron microscopy.