| Introduction Depression is one of most common mental disorders, its pathological mechanism has not yet been completely understood. Increasing evidence supports that depression is related to structural and functional changes in specific regions of the limbic system.Therefore, studying depression has been focusing on how environmental stress factors affect neural plasticity in the limbic system.Objectives1. To reveal the correlation between neural plasticity in the lateral amygdale and the occurrence of depression in the CUMS (chronic unpredictable mild stress) induced rat model of depression.2. To investigate antidepressant-like effect of curcumin and its underlying mechanism(s). Methods A total of48Wistar rats were randomly allocated to one of the following four groups:(a) control group (n=12),(b) CUMS group (n=12),(c) curcumin (40mg/kg)+CUMS (n=12),(d) vehicle (0.1%DMSO,10ml/kg)+CUMS (n=12). Except the non-stressed control animals, rats in the rest of three groups were assigned to one animal per cage in receiving stress treatments. Animals were exposed to stress regime for a continuous six-week period. Curcumin or DMSO was intraperitoneally (i.p.) administered in a constant volume30minutes prior to the stress exposure once a day for six weeks. Following the6-week of stress regime, rats were subjected to a set of behavioral tests that included open-field test, forced swimming test and sucrose preference test. Thereafter, the animals were sacrificed and the lateral amygdala (LA) was subjected to morphological and biochemical examinations. The ultrastructure of the LA was examined with the transmission electron microscope. Immunofluorescence and western blot were performed to determine the changes of BDNF (brain-derived neurotrophic factor), PSD-95(postsynaptic density95) and synaptophysin expression in LA regions. We injected the selective ERK(extracellular regulated protein kinases) antagonist SL327i.p. either alone or at30min prior to the injection of curcumin to explore the effect of curcumin on depressive-like behavior and the mechanism. Results (1) In comparison with non-stressed animals (n=12), animals exposed to CUMS (n=12) had less body weight gain animals (p<0.05). Open-field test showed that CUMS was associated with significantly reduced the number of crossings and rearings. CUMS exposure also significantly increased immobility time and decreased swimming time in rats as compared to the non-stressed animals (p<0.05) in forced swimming test. Sucrose preference test showed that CUMS exposure significantly reduced sucrose consumption as compared to the non-stressed group (p<0.05).(2) In the control group, neurons in the LA showed intact cytoplasm membrane and nuclear membrane; the post-synaptic density (PSD), dendritic spinespre-synaptic vesicles were clearly recognizable. Six-week CUMS exposure resulted in decreases in the number of synapses, surface density and thickness of PSD.(3) Immunofluorescence and Western blot showed a6-wk exposure to CUMS was associated with down regulations of BDNF, PSD-95and synaptophysin expression within the LA region.(4) Animals treated with curcumin had more body weight gain than those untreated CUMS animals. Behavioral tests showed that curcumin increased crossings and rearings in open-field test, decreased immobility time but increased swimming time in forced swimming test and increased sucrose consumption in sucrose preference test. Immunofluorescence and western blot showed that curcumin treatment up-regulated the expression of mature BDNF, PSD-95and synaptophysin within the LA region of CUMS-exposed animals.(5) Up-regulation of BDNF by curcumin was related to the enhanced expression of p-ERK1/2. Conclusions1. CUMS could induce depressive-like behaviors that is associated with synaptic plasticity as evidenced by decreased synaptic density, surface density and thickness of PSD in LA neurons and those molecules that involve in the maintenance of synapses.2. The antidepressant-like action of curcumin appears to be mediated by MAPK/ERK-BDNF signaling pathway. |
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