Study On The Effect Of Environmental Enrichment On Depression-like Behavior And Hippocampal Neuroplasticity In CUMS Model Rats

Objective Observe the effects of environmental enrichment on depression-like behavior,hippocampal neuron morphology,and expression of neuroplasticity-related proteins PKA,CREB,p-CREB,and BDNF in CUMS model rats,and explore the anti-depressant mechanism of environmental enrichment.Methods80 SPF male SD rats were randomly divided into blank control group and model group after removing abnormal behavioral indexes by sucrose preference test and open field test.The rat model of CUMS depression was established by separation combined with chronic unpredictable mild stress for 21 days.Body weight,sucrose preference test,open field test and forced swimming test were used to evaluate the rats in the model group.The successful rats were randomly assigned to model control group(n = 10),non-music-environmental enrichment group(n = 10)and music-environmental enrichment group(n = 10).After 21 days of environmental enrichment intervention,the depression-like behavior of CUMS model rats was observed by sucrose preference test,body weight,forced swimming test and open field test.The morphological changes of neurons in hippocampus were observed by HE staining,and Immunohistochemistry and Western blot were used to detect the expressions of PKA,CREB,p-CREB and BDNF in hippocampus.Results1.The CUMS depression rat model was successfully established: compared with the blank control group,the weight gain,the preference rate of sugar water,the total distance of activities in open field,and the number of rearing in the model group were significantly decreased(p < 0.01),the active distance in the central area was significantly decreased(p < 0.05),and prolonged the swimming immobility time significantly(p < 0.05),suggesting that the establishment of CUMS depression rat model was successful.2.Effect of environmental enrichment on depression-like behavior of CUMS model rats: compared with the model control group,environmental enrichment could significantly increase the sucrose preference rate of CUMS model rats(p < 0.01),prolong the total distance of activities in the open field of CUMS model rats(p <0.05),and shorten the immobility time of forced swimming(p < 0.01).Among them,the central area activity distance of the rats in the non-music-environmental enrichment group was increased(p < 0.05),but the number of rearing had no significant difference(p > 0.05),and the number of rearing in the music-environmental enrichment group were significantly improved(p < 0.01),but there was no significant difference in the central area activity distance(p > 0.05);Compared with the non-music-environmental enrichment group,the time of forced swimming immobility of rats was shortened more obviously in the music-environmental enrichment group(p < 0.05).3.Effect of environmental enrichment on the morphology of hippocampal neuron of CUMS model rats: Compared with the blank control group,the number and layer of cells decreased,the intercellular structure was loose,the outline was blurred,and some of the nuclei were pyknotic,deep stained and ruptured in the hippocampal CA1,CA3 and DG regions of the model control group.The environmental enrichment could significantly improve the number and morphology of cells in the hippocampus of CUMS model rats,and promote the recovery of cell arrangement and compactness.4.Effect of environmental enrichment on neuroplasticity-related proteins in the hippocampus of CUMS model rats: compared with the blank control group,the expression of PKA,CREB,p-CREB,and BDNF protein in the hippocampus of the model control group decreased(p < 0.01),while those in the non-music-environmental enrichment group and the music-environmental enrichment group could up-regulate the expression of the above mentioned proteins in different degrees(p < 0.01,p < 0.05),and the music-environmental enrichment group promoted the expression of these proteins more obviously(p < 0.01,p < 0.05).Conclusion Long-term chronic stress can lead to depression-like behaviors such as loss of pleasure,decreased desire to explore unfamiliar environments,and behavioral despair in rats,which proves that the CUMS depression model was successfully established.Environmental enrichment can improve the depression-like behavior of CUMS model rats,reduce the pathological damage of hippocampal neurons,and its antidepressant mechanism may be related to the up-regulation of PKA,CREB,p-CREB,and BDNF protein expression.Music could increase the anti-depressant effect of environmental enrichment.