Blocking the p38 MAPK Signaling Pathway in the Rat Hippocampus Alleviates the Depressive-like Behavior Induced by Spinal Cord Injury.

Abstract

Patients with spinal cord injury (SCI) may develop depression, which can affect their rehabilitation. However, the underlying mechanism of depression in SCI patients remains unclear. Previous studies have revealed increased p38 MAPK phosphorylation in the rat hippocampus after SCI, accompanied by depression-like behaviors. However, the role of the p38 MAPK signaling pathway in SCI-induced depression remains unclear. In this study, we used an aneurysm clip-induced rat SCI model to investigate whether p38 MAPK phosphorylation in the hippocampus is associated with depression-like behaviors in rats after SCI. Behavioral testing revealed that SB203580, a p38 MAPK signaling inhibitor, reduced depression-like behaviors. Western blotting and morphological analyses showed that SB203580 inhibited the activation of microglia and astrocytes in the hippocampus after SCI. Additionally, SB203580 reduced the expression of tumor necrosis factor α and increased p38 MAPK phosphorylation and the number of bromodeoxyuridine-positive cells in the hippocampus. These findings suggest that SB203580 can inhibit hippocampal remodeling and the neuroimmune response in the rat hippocampus after SCI. Therefore, the phosphorylation of p38 MAPK in the hippocampus plays a key role in the depression-like behaviors induced by SCI. The inhibition of p38 MAPK phosphorylation may represent a mechanism to protect against hippocampal injury induced by SCI.