S100B-immunopositive astrocytes and oligodendrocytes in the hippocampus are differentially afflicted in unipolar and bipolar depression: a postmortem study

Abstract

Background: Previous studies have suggested that affective disorders are characterized by glial pathology. In this context, it has been hypothesized that elevated S100B serum and cerebrospinal fluid levels may represent a suitable surrogate marker. However, brain studies on the cellular distribution pattern of S100B in depressed patients are lacking so far. Such analyses are crucial, since S100B has been detected in various other cell types, even outside the central nervous system.

Methods: Therefore, we performed a first postmortem analysis on this topic in the hippocampus--which is of major importance for emotional and cognitive aspects of affective disorders. S100B-immunopositive astrocytes and oligodendrocytes were evaluated in the alveus and the CA1 pyramidal layer of patients with major depressive disorder (MDD) or bipolar I disorder (BD) compared to controls.

Results: As revealed by the optical disector cell-counting method, the numerical density of S100B-immunopositive astrocytes was bilaterally decreased in the CA1 pyramidal layer of MDD and BD patients compared to controls, whereas only the bipolar group showed a decreased density of S100B-immunopositive oligodendrocytes in the left alveus. These results were not confounded by gender, age, duration of disease, medication dosage, or autolysis time.

Conclusions: Confirming the idea of previous S100B serum and cerebrospinal fluid studies, our data suggest that S100B-immunopositive glia is dysregulated in the brains of depressed patients. These findings are in accordance with animal experiments in rodents showing a reduced astrocytic S100B-immunoreactivity in the hippocampus after pharmacological serotonin depletion (modeling depression).

Keywords: Depression; S-100B; S100 beta; S100B; bipolar disorder; histopathology; major depressive disorder; postmortem.