BRAIN RESEARCH ELSEVIER Brain Research 708 (1996) 59-70 Research report Differential abundance of superoxide dismutase in interneurons versus projection neurons and in matrix versus striosome neurons in monkey striatum Loreta Medina *, Griselle Figueredo-Cardenas, Anton Reiner Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee, 875 MonroeAvenue, Memphis, TN 38163, USA Accepted 12 October 1995 Abstract To investigate whether differences in vulnerability to free radicals might underlie differences among striatal neurons in their vulnerability to neurodegenerative processes such as occur in ischemia and Huntington's disease, we have analyzed the localization of superoxide free radical scavengers in different striatal neuron types in normal rhesus monkey. Single- and double-label immunohisto- chemical experiments were carried out using antibodies against the enzymes copper, zinc superoxide dismutase (SOD1), or manganese superoxide dismutase (SOD2), and against markers of various striatal cell types. Our results indicate that the striatal cholinergic and parvalbumin interneurons are enriched in SOD1 and/or SOD2, whereas striatal projection neurons and neuropeptide Y/somatostatin (NPY +/SS + ) interneurons express only low levels of both SOD1 and SOD2. We also found that projection neurons of the matrix compartment express significantly higher levels of SOD than those in the striosome compartment. Since projection neurons have been reported to be more vulnerable than interneurons and striosome neurons more vulnerable than matrix neurons to neurodegenerative processes, our results are consistent with the notion that superoxide free radicals are at least partly involved in producing the differential neuron loss observed in the striatum following global brain ischemia or in Huntington's disease. Keywords: Superoxide dismutase; Oxygen free radical; Ischemia; Excitotoxicity;Huntington's disease; Neurodegeneration; Basal ganglia 1. Introduction Oxidative stress, or the excess of oxygen free radicals, has been suggested to be involved in the neurodegenera- tive processes occurring in brain ischemia, aging, and neurodegenerative diseases [1,4,8,10,14,28,30,36,44,62]. The susceptibility to oxidative stress seems to differ among brain regions. For example, the hippocampus and the striatum, which are brain regions greatly affected in neu- rodegenerative diseases and ischemia [29,34,35,61], are among the regions most sensitive to oxidative stress [11]. Previous studies have shown that global brain ischemia and Huntington's disease (HD) produce a very selective neurodegeneration pattern in the striatum, with loss of projection neurons and relative sparing of interneurons [2,19,23,24,26,32,33,37,51,58]. In addition, among striatal projection neurons, those located in the patch or striosome * Corresponding author. Fax: (1) (901) 448-7193; e-mail: areiner@utmem2.utmem.edu. 0oo6-8993/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved SSDI 0006-8993(95)01320-2 compartment seem to be more vulnerable than those lo- cated in the matrix compartment [13,38]. Our aim in the present study was to investigate whether differential vul- nerability to oxygen free radicals might underlie selective neuron loss in the striatum, by analyzing the localization of superoxide free radical scavengers in different striatal neu- ron types in normal rhesus monkey. For this purpose, we used antibodies against two major enzymes that are in- volved in the scavenging of superoxide free radicals: (1) copper, zinc superoxide dismutase (SOD1), which is lo- cated in the cytosol; and (2) manganese superoxide dismu- tase (SOD2), which is located in mitochondria. To analyze whether striatal interneurons contain high endogenous lev- els of superoxide free radical scavengers, double-label immunofluorescence experiments were carded out in which striatum was labeled for either SOD1 or SOD2, and for a marker for one of the three major types of striatal interneu- rons (cholinergic neurons, parvalbumin neurons, or neu- rons co-containing neuropeptide Y and somatostatin). Cal- bindin was used as a marker for striatal projection neurons, and also to distinguished the striosome compartment of the