Cellular and subcellular localization of the copper transporter CTR1 in human postmortem hippocampus and striatum

Copper is essential for neurological function, and its transport across the blood-brain barrier (BBB) is mediated by the copper transporter CTR1. Via CTR1, copper enters endothelial cells at the BBB and is transported into astrocytes and neurons. Although critical for homeostasis, copper distribution varies across brain regions and within cells. Knockdown of CTR1 causes developmental defects, highlighting its significance. This study examined CTR1 localization in human postmortem hippocampus and striatum. Postmortem brain samples from unaffected individuals were analyzed using immunohistochemistry, in situ hybridization, and ultrastructural electron microscopy (EM). Immunolabeling was observed in putative endothelial-like, astrocytic-like and oligodendroglial-likeprofiles, pyramidal neurons, and bipolar-appearing interneuronal profiles. Multiplex fluorescent in situ hybridization demonstrated SLC31A1 mRNA signal in neuronal, vascular-associated, and glial-associated cellular populations corresponding to those identified by immunohistochemistry. Using ultrastructural EM, CTR1-associated labeling was observed in axon terminals forming asymmetric synapses in the hippocampus and striatum, including labeling adjacent to vesicular structures. Additionally, CTR1-associated labeling was observed adjacent to mitochondrial profiles in both regions. These findings provide descriptive baseline data on CTR1 localization in human brain and may inform future studies of copper transport in health and disease. disorders.