Effects of ADAR1 inducer / inhibitor on cognitive impairment and the expression of ADAR1 protein of social isolation mice

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), ADAR1inhibitor 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 ADAR1 immunoreactivity and Western blot was 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), CA1: (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. Key words: Social isolation; Cognitive function; BALB/c mice; Adenosine deaminase 1 acting on RNA