| Objective Alzheimer’s disease(AD),is a progressive neurodegenerative disorder without effective treatment.The cognitive symptoms emerge late in AD,and it severely affects patients’ healthy and causes heavy social burdens.The presence of amyloid β peptides(Aβ)is suggested as one of the crucial causative agent of AD pathologies.In addition,accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles and neuroinflammation are pathological hallmarks of the disease.Medical ozone has been shown useful in the treatment of various disease,at nontoxic doses(below 70 μg/m L)facilitated tissues to adapt to oxidative stress by maintaining an equilibrated redox balance and provided a modulation of body’s metabolism.Although ozone therapy is widely used in medical field,however,the effect of ozone on AD has not been researched to date.In this present study,our group aimed to find whether ozone therapy has an effect on AD mouse models,we examined the effects of long-term intraperitoneal ozone injection on cognitive impairment and Aβ deposition in APP/PS1 mouse model.Methods Thirty male APP/PS1 double transgenic mice(APP/PS1 mice)and twenty 5-month-old male C57BL/6J mice(wild-type mice,WT mice)were used in this study.The WT control group and the 50 μg/m L ozone therapy group.The 5-month-old male APP/PS1 mice were randomly separated into three groups as follows: the model control group,the 30 μg/m L ozone therapy group and the 50 μg/m L ozone therapy group.Before and during the ozone injection treatment,ethological tests were performed to analyze the cognitive function and the anxiety emotion of mice.In addition,some molecular and histopathological examination were performed to investigate the protein levels and histomorphology changes.Results(1)In trial 1(visible phase,day 1-3),and trial 2(hidden phase,day 4-8)of the MWM task,APP/PS1 mice showed poor performance compared with the wild-type mice,but the significant difference did not find at every time point.After 21 days of ozone treatment,the daily learning latencies of the mice from AD50 group mice were significantly shorter than those of the mice in the AD group(P<0.05).(2)For the analysis of the probe tests(test 1-4),we recorded the number of plate crossing of three different target areas(target1,2,3).In test 2,AD30 group and AD50 group exhibited increased crossing numbers compared with the AD group.And in test 3,the crossing number of AD50 group significantly increased compared with the AD group.However,all groups were failed to reach significance in test 4(P>0.05).(3)Open field test showed that ozone has no influence in the anxious emotion.(4)Western blot test showed that ozone therapy reduced APP levels in the brains of APP/PS1 mice.And for the prefrontal cortex,the expressions of IBA1 in the WT50 group were significantly increased(P<0.05).For the prefrontal cortex and hippocampal,the ratios of p-AKT/AKT in the mice from the WT50 group was significantly increased,as compared to WT group.However,the expressions of i NOS and Neu N did not change between any of the groups.(5)ELISA test showed the levels of soluble Aβ1-40 and Aβ1-42 in all the groups did not have a significant difference(P>0.05).(6)Histopathological examination showed that ozone therapy can reduce Aβ depositon in APP/PS1 mice.Conclusion This study evaluated the efficacy of ozone administration could alleviate cognitive impairment of APP/PS1 mice and modify the protein levels of APP and Aβ in the prefrontal cortex and hippocampus.Taken together,this investigation showed that ozone intraperitoneal injection could partially improve the behavior performance,suppress the expression of APP and reduce Aβ deposits of APP/PS1 transgenic mice.These findings support that the administration of ozone has a therapeutic potential in APP/PS1 mice. |
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