Synaptic Plasticity, But not Hippocampal Neurogenesis, Mediated the Counteractive Effect of Wolfberry on Depression in Rats

Abstract

Depression is a life-threatening psychiatric disorder characterized with a long-term hypercortisolemia in depressed patients. Based on this clinical feature, hypercortisolemia was mimicked in experimental animals to understand the neuropathogy of depression and to explore new therapeutic strategies. Wolfberry, also known as Lycium barbarum , is a type of common fruit produced in mainland China. Accumulated evidence has shown that the extracts from Lycium barbarum (LBP) had a wide range of neuroprotective effects in various neurogenerative models. However, the antidepressant effect of LBP on depression and its mechanism has not yet been explored. In the present study, we investigated the effects of LBP on counteracting depression using an animal model injected with moderate dose (40 mg/kg) or severe dose (50 mg/kg) of corticosterone (CORT) treatments for 14 days. The results showed that CORT significantly increased immobility time and decreased hippocampal cell proliferation. LBP treatment significantly decreased the immobility time in forced swimming test, a test for the intensity of depressive behaviors, both in 40 and 50 mg/kg CORT stressed rats. Moreover, LBP treatment restored the reduced proliferation of neuroprogentior cells in the hippocampus in 40 mg/kg CORT stressed rats and the neuronal differentiation but not the proliferation in 50 mg/kg CORT stressed rats. After ablation of adult neurogenesis with Ara-c infusion, the beneficial effect of LBP treatment in reducing immobility time was not affected in 40 and 50 mg/kg CORT stressed rats. Golgi staining and Western blotting detection showed that LBP treatment restored the reduced spine density and the decreased level of PSD-95 in the hippocampus caused by 40 and 50 mg/kg CORT, respectively, indicating enhanced synaptic plasticity in the hippocampus. The data showed a novel effect of LBP on reducing depression-like behavior and its antidepressant effect may be mediated by enhanced synaptic plasticity, but not hippocampal neurogenesis.