Cell proliferation is reduced in the hippocampus in schizophrenia

Abstract

Objective: The molecular and cellular basis of structural and functional abnormalities of the hippocampus found in schizophrenia is currently unclear. Postnatal neurogenesis contributes to hippocampal function in animal models and is correlated with hippocampal volume in primates. Reduced hippocampal cell proliferation has been previously reported in schizophrenia, which may contribute to hippocampal dysfunction.

Method: We measured the cell proliferation marker, Ki67, in post-mortem hippocampal tissue from patients with schizophrenia (n = 10) and matched controls (n = 16). Ki67-labelled cells were counted within the dentate gyrus and hilus on sections taken from the anterior hippocampus.

Results: We replicated the finding of a significant reduction in Ki67+ cells/mm² in schizophrenia cases compared to controls (t24 = 2.1, p = 0.023). In our relatively small sample, we did not find a relationship between Ki67+ cells and age overall, or between Ki67 + cells and duration of illness or antipsychotic treatment in people with schizophrenia.

Conclusion: Our results confirm that reduced hippocampal cell proliferation may be present in schizophrenia. Restoring hippocampal neurogenesis may be a potential therapeutic target for the treatment of hippocampal dysfunction in schizophrenia.

Keywords: Ki67; Neurogenesis; hippocampus; proliferation; schizophrenia.

Figure 1.

Representative boundary of region of interest. Ki67+ cells were counted within the region bounded by the granule cell layer (dark brown band of cells), and including the subgranular zone (two-cell wide band under the granule cell layer) and hilus. A straight line drawn between the open ends of the granule cell layer was used to consistently define the boundary of the hilus/CA3 (dashed line). GCL: granule cell layer; SGZ: subgranular zone.

Figure 2.

Representative photomicrographs of Ki67 expression in the in hippocampus. (A) A pair of Ki67+ cells (dark brown) in the hilus of the hippocampus. (B) Ki67+ cells in the hilus (upper inset) and granule cell layer (lower inset). Scale bar = 50 µm.

Figure 3.

Hippocampal cell proliferation in schizophrenia and controls. Ki67+ cell density is reduced in the hippocampus schizophrenia cases compared to controls. *p < 0.05.

Figure 4.

Representative photomicrograph of NeuN expression in the hippocampus. NeuN+ neurons (dark brown) in the granule cell layer of the dentate gyrus (thick band of cells), and in the hilus. The black box indicates the size of the counting box used, and the location of cell counting in the hilus. There was no significant difference in the density of NeuN+ cells in the hilus between schizophrenia cases and controls.