A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

Abstract

The ability to rapidly change gene expression patterns is essential for differentiation, development, and functioning of the brain. Throughout development, or in response to environmental stimuli, gene expression patterns are tightly regulated by the dynamic interplay between transcription activators and repressors. Nuclear receptor corepressor 1 (NCoR1) and silencing mediator for retinoid or thyroid-hormone receptors (SMRT) are the best characterized transcriptional co-repressors from a molecular point of view. They mediate epigenetic silencing of gene expression in a wide range of developmental and homeostatic processes in many tissues, including the brain. For instance, NCoR1 and SMRT regulate neuronal stem cell proliferation and differentiation during brain development and they have been implicated in learning and memory. However, we still have a limited understanding of their regional and cell type-specific expression in the brain. In this study, we used fluorescent immunohistochemistry to map their expression patterns throughout the adult mouse brain. Our findings reveal that NCoR1 and SMRT share an overall neuroanatomical distribution, and are detected in both excitatory and inhibitory neurons. However, we observed striking differences in their cell type-specific expression in glial cells. Specifically, all oligodendrocytes express NCoR1, but only a subset express SMRT. In addition, NCoR1, but not SMRT, was detected in a subset of astrocytes and in the microglia. These novel observations are corroborated by single cell transcriptomics and emphasize how NCoR1 and SMRT may contribute to distinct biological functions, suggesting an exclusive role of NCoR1 in innate immune responses in the brain.

Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice

“…Brain tissues were processed as previously described (Iemolo et al, 2020). Briefly, 30-μm thick coronal slices were stained with a primary antibody recognizing Fos (1:1000, ABE457, EMD Millipore, RRID:AB_2631318) and a secondary anti-rabbit antibody (donkey anti-rabbit Alexa Fluor 488 (1:1000, #A21206, Thermo Fisher Scientific).…”

Reelin deficiency exacerbates cocaine-induced hyperlocomotion by enhancing neuronal activity in the dorsomedial striatum

“…One hour after injection, mice were anesthetized with CO2 and fixed via transcardial perfusion with 4% paraformaldehyde (PFA) in phosphate-buffered saline (PBS). Brain tissues were processed at a cryostat, as previously described 33 . 30-μm thick coronal slices were stained with a primary antibody recognizing Fos (1:1000, ABE457, EMD Millipore, RRID:AB_2631318) and a secondary anti-rabbit antibody (donkey anti-rabbit Alexa Fluor 488 (1:1000, #A21206, Thermo Fisher Scientific).…”

Nuclear Receptor Coactivators (NCOAs) and Corepressors (NCORs) in the Brain

“…NCOR1 and NCOR2 are widely expressed in the adult mouse brain with overall similar neuroanatomical distribution ( 36 ). Immunohistochemistry detected both proteins in all cortical layers of the neocortex, the pyramidal cell layer of the piriform cortex, all subregions of the hippocampus, and striatum.…”

“…Both NCOR1 and NCOR2 are expressed in glutamatergic and GABAergic neurons with no preferential expression in a specific neuronal population versus the other. Microglial and oligodendrocytes in the cortex, hippocampus, and striatum show detectable expression of NCOR1 but not NCOR2 ( 36 ).…”