Neuroprotective effects of cerium oxide nanoparticles on experimental stress-induced depression in male rats

Inflammation and oxidative/nitrative stress induced by chronic psychosocial or physical stress play fundamental roles in the pathogenesis of depression, and lead to the loss of neurotrophic support, decreased neurogenesis and synaptic plasticity in the hippocampus. Findings have shown inhibition of inflammation waterfall may offer new approaches to the treatment of depression, especially for patients with treatment-resistant depression (TRD). Cerium Oxide (CeO₂) is the oxide form of cerium, a rare earth element in the lanthanide series. Cerium oxide nanoparticles (CeO₂NPs) are potent regenerative antioxidant and anti-inflammatory agents. We evaluated the neuroprotective and the neuronal plasticity activities of CeO₂NPs in the stress-induced model of depression.

We have analyzed the effects of single-dose intrahippocampal and intracerebroventricular (ICV) injections of CeO₂NPs treatment on immobility behavior (forced swimming test), hippocampal IL-6 and malondialdehyde (Elisa), cell survival (Nissl staining), dentate gyrus BrdU-positive cells (Immunohistofluorescence) and growth associated protein-43 (GAp-43) expression (Immunohistofluorescence) of the hippocampal CA3 region.

In our study, single-dose CeO₂NPs treatment could effectively suppress inflammatory and oxidative markers level induced by unpredictable chronic mild stress (UCMS) and improved immobility behavior, increased hippocampal cell proliferation, cell survival and neurite outgrowth, and thereby, prevented the progression of hippocampal destruction and dysfunction.

This study demonstrates a new prospect for the treatment of depression. Our study gives us the confidence to continue the investigation of CeO₂ NPs as a novel therapy, especially, for TRD that characterized by chronic and persistent inflammation.