Response of striosomal opioid signaling to dopamine depletion in 6-hydroxydopamine-lesioned rat model of Parkinson's disease: a potential compensatory role

Abstract

The opioid peptide receptors consist of three major subclasses, namely, μ, δ, and κ (MOR, DOR, and KOR, respectively). They are involved in the regulation of striatal dopamine functions, and increased opioid transmissions are thought to play a compensatory role in altered functions of the basal ganglia in Parkinson's disease (PD). In this study, we used an immunohistochemistry with tyramide signal amplification (TSA) protocols to determine the distributional patterns of opioid receptors in the striosome-matrix systems of the rat striatum. As a most striking feature of striatal opioid anatomy, MORs are highly enriched in the striosomes and subcallosal streak. We also found that DORs are localized in a mosaic pattern in the dorsal striatum (caudate-putamen), with heightened labeling for DOR in the striosomes relative to the matrix compartment. In the 6-hydroxydopamine-lesioned rat model of PD, lesions of the nigrostriatal pathways caused a significant reduction of striatal labeling for both the MOR and DOR in the striosomes, but not in the matrix compartment. Our results suggest that the activities of the striosome and matrix compartments are differentially regulated by the opioid signals involving the MORs and DORs, and that the striosomes may be more responsive to opioid peptides (e.g., enkephalin) than the matrix compartment. Based on a model in which the striosome compartment regulates the striatal activity, we propose a potent compensatory role of striosomal opioid signaling under the conditions of the striatal dopamine depletion that occurs in PD.

Distinct migratory behaviors of striosome and matrix cells underlying the mosaic formation in the developing striatum

“…It has been used in many studies for immunohistochemical analyses of MOR in the rat medullary oblongata (Pinto et al, ), the spinal cord (Horvath et al, ; Wang et al, ), and the dorsal root ganglia (Wang et al, ). Our immunohistochemical analyses revealed a staining pattern in the developing striatum consistent with that observed in the previous study using rat MOR antibody that was raised against synthetic peptides from the carboxyl‐terminus of rat MOR (Miura et al, ) and that using a rabbit polyclonal MOR antibody raised against KLH‐conjugated peptides derived from the carboxyl‐terminus of human MOR (Koizumi et al, ).…”

Compartmental function and modulation of the striatum

“…Unlike KORs (the endogenous ligand of which is dynorphin), which are expressed homogenously throughout the striatum, MORs and DORs are enriched in striosomes and exo-patch neurons (Graybiel, 1990;Koizumi et al, 2013;Miura et al, 2007;Smith et al, 2016 (Miura et al, 2007). Unlike KORs (the endogenous ligand of which is dynorphin), which are expressed homogenously throughout the striatum, MORs and DORs are enriched in striosomes and exo-patch neurons (Graybiel, 1990;Koizumi et al, 2013;Miura et al, 2007;Smith et al, 2016 (Miura et al, 2007).…”

“…The striatum expresses three classes of opioid receptors: µ (MORs), ∂ (DORs), and κ (KORs). Unlike KORs (the endogenous ligand of which is dynorphin), which are expressed homogenously throughout the striatum, MORs and DORs are enriched in striosomes and exo-patch neurons (Graybiel, 1990;Koizumi et al, 2013;Miura et al, 2007;Smith et al, 2016). Despite the striosomal expression pattern of MORs and DORs, their endogenous ligand, enkephalin, is positioned to modulate synaptic transmission throughout the striatum.…”

Genetic-Based Dissection Unveils the Inputs and Outputs of Striatal Patch and Matrix Compartments

“…Furthermore, patch/matrix are differentially affected in neurological pathologies such as Parkinson’s disease (Koizumi et al, 2013), Huntington’s disease (Lawhorn et al, 2008), drug addiction (Hurd and Herkenham, 1993), and others (Crittenden and Graybiel, 2011). …”