| Objiective:To explore the expression changes of 5-HT1 AR and TGF-β1in rats with post-stroke depression and the effect of foraging exercise intervention.Methods:Fistly,the right middle cerebral artery occlusion(MCAO)model was established,1 week later,and then combined chronic mild unpredictable stress stimulation(CUMS)with solitary culture was used for 3 weeks to establish post-stroke depression(PSD)model.CUMS includes fasting and water,wet bedding,noise stimulation,ice swimming,and more.The experiment was divided into 4 groups:sham operation group,stroke(I/R)group,PSD group and PSD+foraging exercise group,and the exercise group intervened for 4 weeks.After MCAO(1week),CUMS(4 weeks)and exercise intervention(8 weeks),four groups of rats were evaluated for weight,sucrose preference tests(SPT),open field test(OFT)and novel feeding test(NSFT).At 8 weeks,rats brain tissues were taken for TTC staining to calculated the volume of cerebral infarction.HE staining was used to observe pathological changes in the prefrontal lobe,hippocampal CA1,CA3 and dentate gyrus(DG);immunohistochemistry and Western Blot technology was used to detect the expression of 5-HT1 AR and TGF-β1 protein in frontal lobe and hippocampus.Result:(1)The change of weight: At 1 week,there was no significant difference among the 4 groups(P=0.095).At 4 weeks,compared with I/R group,the weight of PSD group was significantly reduced(P <0.01).At 8 weeks,the weight of rats in all four groups increased,compared with PSD group,the weight of PSD+exercise group significantly increased(P<0.01).(2)Behavioral testing result:1 Sucrose preference tests:At 1 week,there was no difference in the proportion of sucrose preference among the 4 groups(P=0.653).At4 weeks,compared with I/R group,the proportion of sucrose preference in PSD group was significantly lower(P < 0.01).At 8weeks,compared with PSD group,the proportion of sucrose preference in PSD+exercise group was significantly increased(P=0.001).2 Open field test:At 1 week,there was no difference in the scores of horizontal movement(P=0.973)and vertical movement(P=0.968)among the four groups.At 4 weeks,compared with I/R group,the scores of horizontal and vertical movement in PSD group were significantly lower(P < 0.01).At 8 weeks,compared with PSD group,the score of horizontal movement(P=0.001)and vertical movement(P=0.004)in PSD+exercise group increased.Compared with I/R group,the score of vertical movement in PSD+exercise group was lower(P=0.026).3 Novelty suppressed feeding tests:At 1 week,there was no difference in the incubation period(P=0.939)and food consumption(P=0.917)among the four groups.At 4 weeks,compared with I/R group,the incubation period were prolonged and food consumption were decreased in PSD group(P<0.01).At8 weeks,compared with PSD group,the incubation period of PSD+exercise group was shorter(P < 0.01),and the food consumption was increased(P=0.005);Compared with I/R group,the incubation period of PSD+exercise group was longer(P=0.018).(3)TTC staining:At 8 weeks,in addition to sham operation group,the remaining three groups all had infarct areas of varying degrees.Compared with I/R group,the volume of cerebral infarction was increased in PSD group(P=0.001)and PSD+exercise group(P=0.003).There was no significant difference in the volume of cerebral infarction between PSD+exercise group and PSD group(P=0.626).(4)HE staining:At 8 weeks,HE staining results of frontal lobe of rats:Neurons in sham operation group were normal in morphology,evenly stained in nucleus and cytoplasm,and arranged orderly;Neurons in I/R group were decreased,some cells were round,and arranged slightly disorderly;Neurons in PSD group were decreased,and their shapes were round or oval,with obvious nuclear pyknosis,rupture,deep staining,uneven cytoplasmic staining,and disordered arrangement;The neuron morphology of PSD+exercise group was roughly the same as PSD group,and the number was significantly increased compared with PSD group.The results of HE staining in hippocampal CA3 and DG areas were similar to those in frontal lobe.(5)Immunohistochemical staining:At 8 weeks,TGF-β1 staining in the frontal lobe of rats was brown.Compared with PSD group(P=0.001)and I/R group(P=0.004),the expression of TGF-β1 positive cells in PSD+exercise group was significantly increased.Hippocampal CA1area:Compared with PSD group and I/R group,the number of TGF-β1positive cells in PSD+exercise group increased significantly(P <0.01).Hippocampal CA3 and DG areas:TGF-β1 positive cell counts were basically consistent with hippocampal CA1 area.(6)Western blot:Frontal lobe results at 8 weeks:Compared with PSD group and I/R group,the expression of 5-HT1 AR protein in the frontal lobe was increased in PSD+exercise group(P<0.01).Compared with PSD group and I/R group,the expression of TGF-β1 protein in frontal lobe was up-regulated in PSD+exercise group(P<0.01).Hippocampal results at 8 weeks:Compared with PSD group(P=0.001)and I/R group(P=0.006),5-HT1 AR protein expression in the hippocampus of PSD+exercise group was up-regulated.Compared with PSD group,the expression of TGF-β1 protein in the hippocampus was up-regulated in PSD+exercise group(P<0.01);Compared with I/R group,the expression of TGF-β1 in the hippocampus of PSD+exercise group was up-regulated(P=0.007).Conclusion:(1)Foraging exercise can alleviate depression and improve depression behavior in PSD rats;(2)Chronic stress can reduce the expression of 5-HT1 AR and TGF-β1 in the frontal lobe and hippocampus of PSD rats;(3)Foraging exercise intervention can increase the expression of5-HT1 AR and TGF-β1 in the frontal lobe and hippocampus,thereby improve the brain pathology and depressive behavior symptoms of rats. |
