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Objective To observe the effect of enriched environment (EE) on the pain threshold and depression like behavior in mice with chronic constriction injury (CCI) and the underly ing mechanism.Methods Sixty C57/BL6 mice were equally randomized into five groups:sham operation group (group Sham),CCI+standard environment(SE) group (group CS),CCI+EE group (group CE),CCI+EE+temozolomide group (group CET),CCI+EE+lipopolysaccharide group (group CEL).The paw withdraw threshold (PWT),paw withdraw latency,forced swim test (FST)and sucrose preference test (SPT) were evaluated,after the operation,meanwhile the hippocampal bromodeoxyuridine (Brdu),ki67 and doublecortin (ICX) positive cells,tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) were determined.Results Compared with group Sham,the PWT,PWL,sucrose consumption and Brdu,Ki67,DCX positive cells were significantly decreased,the immobility time and levels of TNF-α and IL-1β were obviously increased in group CS (P＜0.05).Compared with group CE,the PWT,PWL,sucrose consumption and Brdu,Ki67,DCX positive cells were significantly decreased in groups CS and CEL.The immobility time was obviously increased in groups CS,CET and CEL,moreover,the levels of TNF-α and IL-1β were significantly increased in groups CS and CEL (P＜0.05).Conclusion EE can improve the neuropathic pain,depression-like behavior and neural regeneration in mice with CCI.The inhibition of neural regeneration can block EE-induced improvement of depression-like behavior,but does not affect the pain threshold in mice with CCI.The augmentation of central inflammation can attenuate EE-induced improvement of pain threshold and depression-like behavior in mice with CCI.
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Objective To observe the variation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and microglia in the comorbidity of neuropathic pain and depression and discuss the related mechanism.Methods The spared nerve injury model was used.Forty-four male adult Sprague Dawley rats were randomly divided into the following four groups (n=11 each): sham+vehicle group (group SV), sham+APO group (group SA), SNI+vehicle group (group SNV), SNI+APO group (group SNA).In groups SA and SNA, rats were intraperitoneally injected with apocynin (APO) 15 mg/kg 24 hours and 1 hour before SNI and continued once daily until the 14th day.The rats in the other two groups received the equal volume of vehicle.The mechanical withdrawal threshold (MWT) was tested 1 day before SNI and 7 days and 14 days after SNI, and the open field test, the forced swimming test and the sucrose preference test were performed 14 days after SNI.The prefrontal cortex were collected 2 hour after the behavior tests.The expression of gp91phox was detected by Western blot and the expression of Iba1 and gp91phox were detected by double-immunofluorescance staining.Results The reduced MWT, the increased immobility time, the decreased sucrose consumption and the increased content of gp91phox were observed in group SNV compared with groups SV, SA and SNA (P<0.05).The expression of Iba1 and gp91phox were increased in group SNV.The total travel distance in the open field test and the total liquid consumption in the sucrose preference test had no significant difference among the four groups.Conclusion Neuropathic pain may induce depressive behaviors and activate NADPH oxidase in the prefrontal cortex.Moreover, the inhibition of NADPH oxidase by APO can alleviate neuropathic pain and depression, which is potentially related to the activation of microglia.
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Objective To observe changes of hippocampal levels of pro-inflammatory cytokines in rats with neuropathic pain-induced depression, and to explore the relationship between hippocampal levels of pro-inflammatory cytokines and severity of depression.Methods Twenty-eight adult male rats were randomly divided into two groups: group sham (n=14) and spared nerve injury (group SNI) (n=14).Mechanical withdrawal thresholds (MWT) were measured 1 day before and 7, 14 and 21 days after operation.Sucrose preference test and forced swim test were tested 1-3 days before and 21-23 days after operation.After test, hippocampus was collected.The hippocampal levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Correlational relationships between hippocampal levels of pro-inflammatory cytokines and sucrose preference were evaluated.Results Compared with group sham, MWT was decreased 7, 14, 21 days after operation (P<0.001).Group SNI displayed decreased sucrose preference 21 days after operation (P<0.01) and increased immobility time in FST 23 days after operation (P<0.05).The levels of IL-6 and TNF-α were increased in hippocampus (P<0.05 or P<0.01).No significant difference was observed in IL-1β.The hippocampal levels of IL-1β (r2=0.60,P<0.01), IL-6 (r2=0.55,P<0.01) and TNF-α(r2=0.60,P<0.01) were negatively correlated with sucrose preference.Conclusion The hippocampal levels of pro-inflammatory cytokines IL-6 and TNF-α are increased in rats with depression induced by neuropathic pain, and the levels of hippocampal pro-inflammatory cytokines are negatively correlated with the severity of depression.
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Objective To observe the effects of enriched environment on cognitive function in mice with sepsis-associated encephalopathy and to study the neuron PAS domain protein 4 (NPAS4)/brain deprive neurotrophic factor (BDNF)related mechanisms.Methods Sixty adult male mice were divided randomly into three groups:sham operation with standard environment group (group SS,n =12),cecal ligation and puncture with standard environment group (group CS,n =24),cecal ligation and puncture with enriched environment group (group CE,n =24).All mice were reared in standard environment or enriched environment for 28 days.The fear condition test was conducted on day 29 af-ter operation in mice.The change of NPAS4 and BDNF,the density of dendritic spine were detected by western blot or golgi staining.Results Compared with group SS,the context freezing time, NPAS4 and BDNF expression and the density of dendritic spine in hippocampus decreased significantly in group CS (P < 0.05).Compared with group CS,the context freezing time,NPAS4 and BDNF expression and the density of dendritic spine in hippocampus increased significantly in group CE (P <0.05).No significant difference was observed in the conditional freezing time among three groups.Conclusion Enriched environment can obviously improve cognitive function impairment induced by sepsis-associated encephalopathy,which may be related with up-regulated expression of NPAS4/BDNF,and promoted synaptic plasticity.