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Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.
ABSTRACT
Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.
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ObjectiveTo explore the effects of social isolation on the cognition and expression of 5-HT2C receptor(5-HT2CR) and adenosine deaminase that act on RNA 1(ADAR1) in BALB/c mice.MethodsThe healthy BALB/c mice were isolated for 2,4,and 8 weeks individually since postnatal 21 days respectively to set up isolation mice model,the same age mice without isolation were regarded as control group.The new object location and the new object recognition tests were used to measure the spatial and non-spatial cognitive function,and western blot was used to measure the protein expression of 5-HT2CR and ADAR1.ResultsThe new object location test showed that the spatial discrimination index (DI) of BALB/c mice isolated for 2 weeks was decreased significantly compared with the control group(control group was (0.075±0.340),isolation group was (-0.653±0.308),P<0.05),and no obvious difference was found for the group isolated for 4 and 8 weeks.The new object recognition test showed that the non-spatial DI of BALB/c mice isolated for 2 and 4 weeks were decreased significantly compared with the control group(control 2 weeks group was (0.088±0.210),isolation 2 weeks group was (-0.945±0.194),P<0.05;control 4 weeks group was (0.105±0.267),isolation 4 weeks group was (-0.506±0.215),P<0.05),and no obvious difference was found for the group isolated for 8 weeks.Compared with the control group the expression of 5-HT2CR and ADAR1 in the hippocampus were decreased significantly for the group isolated for 2 weeks.(5-HT2CR:control group was (1.025±0.144),isolation group was (0.891±0.026),P<0.05.ADAR1: control group was (0.839±0.120),isolation group was (0.629±0.094),P<0.05).ConclusionsTwo week social isolation results in the decrease of spatial and non-spatial cognitive function in BALB/c mice,in the meanwhile,social isolation stress results in the obvious decrease of 5-HT2C receptor and ADAR1 protein expression in the hippocampus of BALB/c mice.
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Objective To study the effect of social isolation( SI) on the exploratory behavior and working memory in mice. Methods The Kunming mice of postnatal 21 days were divided into the control group,SI 2 weeks group,SI 2 weeks gregarious group,SI 4 weeks group and SI 8 weeks group,according to randomized design with ten animals each. All isolated mice were isolated for 2, 4 and 8 weeks respectively, the gregarious group were housed under normal grouped housing enviroment after isolation until adult, the mice with the relative same age were control groups. All animals were measured for exploratory behavior and working memory by performing open field and T?maze after the treatment. Results In the open field,compared to the relative control group,the central area of the total time in the SI 4 weeks group(0.07±0.04) was less than the control (0.10±0.04) obviously. The central area percentage of total time in SI 8 weeks group (0.64±0.12) were more than the control (0.43±0.08). In the T?maze,the alteration times in SI 2 weeks group (first day (5.92±0.79),second day (6.67±1.3),third day (7.42±1.08),fourth day (8.17±1.27)) were less than the control (first day (6.80±1.14); second day (7.60± 0.84);third day (8.30±0.95);forth day (9.20±1.32)). However,the alteration times of gregarious group showed no obvious change. Both the alteration times of SI 4 weeks (8.18±1.99) in the second day and that of SI 8 weeks (8.29±3.04) in the forth day were more than the control (6.60±2.11) and (7.80±2.53) respectively.Conclu?sions Working memory of SI 2 weeks rats decrease,which can be improved by the resocialization.SI 4 weeks and 8 weeks rats show the decreasing exploring ability and increasing anxiety and work memory.
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Objective To study the effects of social isolation (SI)on the spatial and nonspatial cognitive ability in mice.Methods The postnatal 21 day kunming mice were divided into control group,SI 2 weeks group,SI 4 weeks group,SI 8 weeks group and SI 2 weeks gregarious group according to randomized block design,with ten animals each.SI 2 weeks group,SI 4 weeks group and SI 8 weeks group were isolated for 2,4 and 8 weeks respectively,SI 2 weeks gregarious group would be housed under normal grouped housing condition after 2 weeks isolation until adult,the relative control groups were the same age as the relative SI and SI gregarious group.All animals were measured the spatial and nonspatial cognitive ability by carrying the object recognition test(ORT) and object location test (OLT) after the treatment.Results In the ORT,compared to the relative control group,the discrimination index in the SI 2 weeks group,SI 4 weeks group and SI 8 weeks group ( ( - 0.03 ± 0.003 ),( - 0.11 ±0.02) and( - 0.21 ± 0.02 ) respectively) were strikingly lower than the relative control group ( ( 0.29 ± 0.03 ),(0.13±0.07) and (0.09 ±0.03) respectively) (P＜0.05).In the OLT,compared to the relative control group,the discrimination index in the SI 2 weeks group,SI 4 weeks group and SI 8 weeks group( ( -0.15 ±0.02),( -0.30± 0.02),( - 0.32 ± 0.02 ) respectively ) were strikingly lower than the relative control group ( (0.33 ± 0.02 ),(0.41 ± 0.03 ),(0.27 ± 0.04)respectively)(P＜ 0.05 ),while the SI 2 weeks gregarious group with the resocialization to the normal housing condition showed no change.Conclusions 2 weeks,4 weeks and 8 weeks isolation on mice lead to the spatial and nonspatial cognition deficits,while the resocialization to the normal housing condition could recover the damage.