| Objective: C-C motif chemokine ligand 11(CCL11),also knowed as Eotaxin-1,was first discovered as a chemotactic activator of eosinophils in animal asthma tests.Recent evidence suggests that CCL11 also plays a role in brain disease.Elevated levels of CCL11 have been detected in a number of neuroinflammatory diseases such as multiple sclerosis,neurodegenerative diseases such as Alzheimer’s disease,and psychiatric disorders such as depression and schizophrenia.Elevated levels of CCL11 have also been found to be associated with neurocognitive deficits in aging,neurodegenerative diseases,and major psychiatric disorders.However,it is still unclear whether CCL11 plays a role in the pathogenesis of depression and its mechanism.Therefore,this study explores the role of CCL11 in the depression-like behaviors of mice induced by chronic social defeat stress and the possible mechanism.Methods: Chronic social defeat stress(CSDS)model of C57BL/6J mice was used.The social interaction test(SIT)and sucrose preference test(SPT)were used to evaluate the depression-like behaviors.Real-time quantitative polymerase chain reaction(RT-q PCR)was used to detect CCL11 m RNA expression levels in peripheral blood,hippocampus and other brain regions of control and susceptible mice.To investigate the role of CCL11 in depression-like behaviors in mice and its possible mechanism,recombinant CCL11 protein,CCL11 neutralizing antibody and CCR3 antagonist were administered to different brain regions.After CSDS modeling,the classic antidepressant fluoxetine was injected intraperitonelly to reverse the depression-like behaviors,and changes of CCL11 levels in peripheral blood and hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).Results:(1)After CSDS,the stress susceptible mice represented as decreasing of the social interaction ratio and sucrose preference ratio.(2)RT-q PCR showed that the level of CCL11 m RNA was significantly increased in the hippocampus,including dorsal hippocampus(d HIP)and ventral hippocampus(v HIP),as well as the subregions of hippocampus like CA1 and CA3,but not in the anterior cingulate cortex(ACC),medium prefrontal cortex(m PFC)and nucleus accumbens(NAc).(3)CCL11 was specifically expressed in astrocytes in hippocampal.(4)ELISA showed that the levels of CCL11 in serum and v HIP brain of stress-sensitive mice were significantly higher than those of the control group.(5)After intraperitoneal injection of CCL11 recombinant protein with carrier and carrier-free CCL11 recombinant protein,it was found that carrier-free CCL11 recombinant protein could improve the stress vulnerability of mice.(6)The immobile time of mice in TST was increased by injecting 500 ng/ml of CCL11 in v HIP.The locomotor ability and anxiety-like behaviors of mice were not affected by the administration of CCL11 recombinant protein.(7)Administration of CCL11 in d HIP did not affect depression-like behaviors,motor ability and anxiety-like behaviors in mice.(8)The administration of CCL11 neutralizing antibody in the v HIP reversed depression-like behaviors,representing as the decreased social interaction ratio in the SIT and increased immobility time in the TST in susceptible mice after CSDS.(9)CSDS exposure had no effect on CCR3 expression in all brain regions.(10)Administration of the CCR3 antagonist SB297006 at v HIP blocked depression-like behaviors induced by administration of the CCL11 recombinant protein.(11)CCR3 was specifically expressed in neurons in the hippocampus.(12)Chronic intraperitoneal injection of fluoxetine can improve the depression-like behaviors of CSDS susceptible mice,and the concentration of CCL11 in serum and v HIP tissues of susceptible mice after fluoxetine administration decreased.Conclusion: CCL11 expression in peripheral blood and hippocampus of mice was increased by CSDS.Administration of CCL11 in the v HIP could induce depression-like behavior through its receptor CCR3.Fluoxetine,the classic antidepressant,could reduce CCL11 levels in the peripheral blood and hippocampus of mice. |
