Expression of Heparan Sulfate Endosulfatases in the Adult Mouse Brain: Co-expression of Sulf1 and Dopamine D1/D2 Receptors.

Ken Miya,Takuya Okada,Kazuko Keino-Masu,Masayuki Masu,Kenta Kobayashi

doi:10.3389/fnana.2021.726718

Abstract

The heparan sulfate 6-O-endosulfatases, Sulfatase 1 (Sulf1), and Sulfatase 2 (Sulf2), are extracellular enzymes that regulate cellular signaling by removing 6-O-sulfate from the heparan sulfate chain. Although previous studies have revealed that Sulfs are essential for normal development, their functions in the adult brain remain largely unknown. To gain insight into their neural functions, we used in situ hybridization to systematically examine Sulf1/2 mRNA expression in the adult mouse brain. Sulf1 and Sulf2 mRNAs showed distinct expression patterns, which is in contrast to their overlapping expression in the embryonic brain. In addition, we found that Sulf1 was distinctly expressed in the nucleus accumbens shell, the posterior tail of the striatum, layer 6 of the cerebral cortex, and the paraventricular nucleus of the thalamus, all of which are target areas of dopaminergic projections. Using double-labeling techniques, we showed that Sulf1-expressing cells in the above regions coincided with cells expressing the dopamine D1 and/or D2 receptor. These findings implicate possible roles of Sulf1 in modulation of dopaminergic transmission and dopamine-mediated behaviors.

Highlights

Heparan sulfate proteoglycans (HSPGs) are glycoproteins present on the cell surface and in the extracellular matrix (ECM) of all animal cells
When AAV5-hSyn-double-floxed inverted open reading frame (DIO)-mCherry virus was injected into the nucleus accumbens shell (NAcSh), the striatum (TS), prefrontal cortex (PFC), and paraventricular nucleus of the thalamus (PVT), many mCherry-positive cells were observed in the corresponding regions, and the mCherry signals were overlapping with the Sulfatase 1 (Sulf1) expression revealed by β-galactosidase immunostaining (Figure 9A)
We examined the co-localization with β-galactosidase and mCherry at the cellular level (Figure 9B)

Summary

Introduction

Heparan sulfate proteoglycans (HSPGs) are glycoproteins present on the cell surface and in the extracellular matrix (ECM) of all animal cells. HSPGs exert a wide variety of biological functions via the interactions among HS and growth factors, morphogens, ECM molecules, and enzymes (Perrimon and Bernfield, 2000; Bishop et al, 2007). During their biosynthesis, HS chains undergo a series of modifications including deacetylation, epimerization, and sulfation, which together generate the enormous structural heterogeneity of HS (Perrimon and Bernfield, 2000; Bishop et al, 2007).

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Conclusion