CLUSTERIN (SGP-2) - A MULTIFUNCTIONAL GLYCOPROTEIN WITH REGIONAL EXPRESSION IN ASTROCYTES AND NEURONS OF THE ADULT-RAT BRAIN

Clusterin (SGP-2) is a newly described glycoprotein associated with se veral putative functions including responses to brain injury. This stu dy reports the regional and cell type expression of clusterin mRNA and its encoded glycoprotein in the rat brain; a limited comparison was a lso done with the human brain. Using in situ hybridization combined wi th immunocytochemistry, we found that astrocytes and neurons may expre ss clusterin mRNA in the normal adult brain. While astrocytes througho ut the brain contained clusterin mRNA, there was regional selectivity for neuronal clusterin expression. In the striatum, clusterin mRNA was not detected in neurons. Only a subset of substantia nigra dopaminerg ic neurons or locus ceruleus noradrenergic neurons (tyrosine hydroxyla se immunopositive) contained clusterin mRNA. However, neuronal cluster in mRNA was prevalent in pontine nuclei and in the red nucleus of the midbrain tegmentum. Similarly, clusterin mRNA was prevalent in both ra t and human hippocampal neuron-specific enolase immunopositive pyramid al neurons, although rat CA1 neurons had less mRNA than CA2-CA3 neuron s. Monotypic primary cell cultures from the neonatal rat showed cluste rin mRNA in both neurons and astrocytes, but not in microglia. By immu nocytochemistry, no clusterin immunopositive glia were observed in any region of the rat brain, confirming previous studies. However, cluste rin immunopositive cells (putative neurons) were observed in the Purki nje cell layer of the cerebellum, medial and interposed cerebellar nuc lei, trigeminal motor nucleus, and red nucleus. Finally, in vitro stud ies suggest that astrocytes, but not neurons, secrete clusterin, which is pertinent to clusterin immunodeposits found after experimental les ioning.