Hippocampal Glial Alterations Are Associated with Mitochondrial Changes and Reduced Glucocorticoid Receptor Density in Suicides

Suicide is a major public health concern frequently associated with depressive disorders and neurobiological alterations within the hippocampus. This study investigated biomarkers related to neuroinflammation, oxidative/nitrosative stress, and mitochondrial labeling in the CA1 region of the hippocampus of young and adult individuals of Mexican ancestry who died by suicide. Postmortem hippocampal CA1 samples were obtained from young and adult suicide cases and age-matched controls. Cellular markers of microglia (ionized calcium-binding adapter molecule 1, Iba1) and astrocytes (glial fibrillary acidic protein, GFAP), neuronal density, glucocorticoid receptor expression, and mitochondrial labeling were evaluated and compared among groups. Suicide cases exhibited increased microglial and astrocyte cell density indicated by increased Iba1 and GFAP immunoreactivity in both age groups. In contrast, mitochondrial labeling and glucocorticoid receptor immunoreactivity were reduced in suicide cases, regardless of age. Additionally, a significant reduction in neuronal density was detected exclusively in young individuals who died by suicide. Together, these findings indicate age-independent alterations in glial immunoreactivity, mitochondrial labeling, and glucocorticoid receptor expression, alongside reduced neuronal density in the hippocampal CA1 region of younger suicide cases, supporting the involvement of neuroinflammation-related processes in suicide. Despite the limited sample size, these findings provide insight into potential neurobiological mechanisms underlying suicide and may contribute to the identification of biomarkers and therapeutic targets for individuals at risk.