Immunohistochemical analysis of Sigma-1 receptor (σ-1R) expression in human pineal gland in relation to different causes of death

•The pineal gland is a photo-neuro-endocrine organ.•The pineal gland connects the outside world to biochemical and physiological functions of the human body.•It is described σ-1R expression in cerebral cortex, cerebellum, hippocampus, pineal gland.•The possible involvement of σ-1R and DMT in psychological stress is reported.•This study demonstrates immunohistochemically the presence of σ-1R in pineal gland. Sigma-1 receptor (σ-1R) modulates cellular signaling pathways, probably acting as a ligand operated chaperone. When activated, the receptor translocates from the interface mitochondrion associated membrane of the endoplasmic reticulum to the cell membrane. σ-1R was demonstrated in some brain regions, including the pineal gland, and was proposed to be involved in several cerebral processes, including neuroprotective responses against homeostasis alterations. On this basis, the immunohistochemical expression of σ-1R in human pineal glands was evaluated, with particular regard to the different causes of death. Thirty-eight pineal glands obtained from forensic autopsies were divided into five groups according to the cause of death: sudden death, drowning, fire fatality, hanging, and hemorrhagic shock, and examined with hematoxylin-eosin stain and immunohistochemistry for σ-1R. Both pinealocytes and perivascular spaces were evaluated. The pineal glands from sudden death were only mildly positive for σ-1R, while a more evident immunopositivity was observed in hanging, fire fatality, hemorrhagic shock, and drowning. These results were confirmed in a two-by-two comparison between the sudden death group and other groups. Our data demonstrate for the first time with immunohistochemical techniques the presence of σ-1R expression in the human pineal gland and propose a direct correlation between σ-1R expression and duration of the death process, in particular when hypoxic conditions and/or excessive psychological stress are present.