Progressive Supranuclear Palsy (PSP) is a primary 4-repeat tauopathy characterized by progressive motor and cognitive decline. Like other tauopathies, tau misfolding and aggregation are prominent but yield PSP-specific features such as tufted astrocytes and globose neurofibrillary tangles. Emerging evidence suggests that nuclear speckle disassembly and mislocalization of RNA-binding proteins, including serine/arginine repetitive matrix protein 2 (SRRM2), may contribute to disease progression, though SRRM2’s role in PSP remains unclear. To assess its association with tau pathology, we examined SRRM2 distribution in midbrain neurons, as well as in astrocytes from both cortical and midbrain regions, using post-mortem immunohistochemistry, immunofluorescence, and 3D reconstruction. In PSP midbrain, neuronal SRRM2 immunoreactivity was markedly elevated compared to controls and co-localized with pTauS396, with >80% overlap; co-localization strongly correlated with SRRM2 abundance (r = 0.9809, p = 0.0191). 3D analysis revealed heterogeneity across cases (PSP-1 to PSP-4) in aggregate morphology, SRRM2 levels, and tau associations. In tufted astrocytes, pTauS396 signals were detected in PSP-1 cortex and PSP-4 midbrain. SRRM2 was absent or faint, yet 3D imaging revealed near-complete SRRM2–pTauS396 co-localization (99% in PSP-1 cortex, 89% in PSP-4 midbrain), regardless of SRRM2 abundance. These findings highlight SRRM2 association with pTauS396 in tangle of PSP.

Astrocytes are the most common glial cells in the mammalian central nervous system. Their diverse structures and functions, along with their critical role as key regulators of brain activity, have recently gained recognition. However, the lack of specific cell markers makes it difficult to identify particular subpopulations. In this study, we examined the distribution of traditional astrocyte markers—glial fibrillary acidic protein (GFAP), SRY-box9 (SOX9), and S100 protein beta (S100β)—in the adult mouse brain. In the cerebral cortex, striatum, and thalamus, most cells did not express GFAP, with limited overlap between GFAP and either SOX9 or S100β. In contrast, the pons-medulla showed a higher rate of co-expression of GFAP and SOX9 compared to the cerebral cortex. In the hippocampus, GFAP was widely expressed and showed significant overlap with SOX9 and S100β. Co-staining of SOX9 and S100β was frequently observed in the cerebral cortex, striatum, thalamus, and midbrain, and S100β-positive cells were more common than SOX9-positive cells. These results reveal regional differences in astrocyte marker expression, highlight the limitations of relying on a single marker like GFAP, and underscore the importance of using multiple markers.

G protein–coupled receptor 37 (GPR37) and GPR37-like 1 (GPR37L1) are orphan G protein–coupled receptors enriched in the central nervous system. However, their cellular distribution in pituitary tissue remains unclear. Here, we mapped Gpr37l1 expression in the adult rat anterior pituitary and identified the expressing cell type(s). Quantitative real-time PCR demonstrated that Gpr37l1 mRNA is significantly more abundant than Gpr37 in the anterior lobe. In situ hybridization (ISH) revealed sparsely distributed Gpr37l1-positive cells throughout the anterior lobe, and the signals did not colocalize with major hormone-producing cell types. Combined ISH and immunohistochemistry further showed that Gpr37l1 mRNA is localized to S100B protein-immunoreactive cells, commonly referred to as folliculo-stellate (FS) cells, and that only a subset of S100B-positive FS cells expresses Gpr37l1. Single-cell RNA-seq analysis corroborated these findings, as Gpr37l1-expressing cells were distributed within the broader S100b-expressing cluster, without forming a distinct subcluster, while showing no detectable Gpr37l1 expression in endocrine lineages or vascular-associated cell populations. Together, these data provide a cell-type–resolved map of Gpr37l1 expression in the adult rat anterior pituitary and identify Gpr37l1 as a marker of heterogeneity within FS cells, establishing a foundation for future studies on GPR37L1 signaling in pituitary microenvironmental regulation.