Comprehensive Analysis of Age- and Sex-Related Expression of the Chaperone Protein Sigma-1R in the Mouse Brain

Sigma-1R (S1R) is a ubiquitously distributed protein highly expressed in the brain and liver. It acts as a ligand-inducible chaperone protein localized at the endoplasmic reticulum. S1R participates in several signaling pathways that oversee diverse cellular and neurological functions, such as calcium and proteome homeostasis, neuronal activity, memory, and emotional regulation. Despite its crucial functions, S1R expression profile in the brain with respect to age and sex remains elusive. To shed light on this matter, we assessed S1R distribution in the mouse brain across different developmental stages, including juvenile, early adult, and middle-aged mice. Using immunohistochemistry, we found that S1R is predominantly expressed in the hippocampus in juvenile mice, particularly in CA1 and CA3 regions. Notably, S1R is not expressed in the subgranular layer of the dentate gyrus of juvenile mice. We observed dynamic changes in S1R levels during development, with most brain regions showing either an abrupt or gradual decline as mice transition from juveniles to adults. Sexual dimorphism is observed before puberty in the hippocampus and hypothalamus and during adulthood in the hippocampus and cortex.