Effects Of Transcranial Electrical Stimulation On Cognitive Function In Normal Aged And APP/PS1 Double Transgenic Mice

Alzheimer’s disease(AD)is the most common neurodegenerative disease with a high proportion of morbidity,incidence and disability,leading to a potential threat to human health.The main clinical manifestations of AD are cognitive declines,various neuropsychiatric and behavioral symptoms,and final loss of self-care ability.To date,the pathogenesis of AD is still unclear.There are several theroies mainly including amyloid β(Aβ)plaques and hyperphosphorylated tau protein.The AD treatments involve drug therapies and non-drug therapies.However,effective drug therapies that can slow or cure the disease are lacking.Transcranial electrical stimulation(t ES)is a non-invasive method of brain electrical stimulation,which includes transcranial direct current(tDCS)and alternating current stimulation(tACS).Both stimulations can regulate the nervous system.Accumulating evidences suggest that the neural mechanism involves an adjustment of balance in neurotransmitter systems between excitation and inhibition,changes of neural plasticity,and so on.There are recent advances in that tACS and tDCS restore the cognitive function degenerated with age.However,the researches on animal models of tACS and tDCS are limited,especially on their assessment of therapeutic effects in AD brain.This study aimed to investigate the effects of tDCS and tACS on cognitive function and neurological activity in normal aging mice and APP/PS1 double transgenic AD mice.First,we conducted experiments on normal aging mice to compare the differences of cognitive and behavioral indices before and after transcranial electrical stimulation,by using open field,Morris water maze,two-trial Y-maze,and novel object recognition tasks.Secondly,we conducted experiments on AD mice model and compared their behavioral and electrophysiological difference before and after transcranial electrical stimulation with self-control design.We recorded EEGs from the prefrontal cortex(PFC),hippocampus(Hip),and occipital cortex(Ctx,serving as a control)in mice under spontaneous state,during Y-maze task performance,and during open-field task performance.The main results are as follows.(1)For the normal aging mice,before stimulation,there were differences in cognition between early and late senescence mice.In total,the learning and memory performance of mice in water maze and the ability to explore open fields and new objects are reduced in the process of aging.The recognition memory of Y-maze and new objects of mice are affected at the early stage of aging.But the memory showed recovery at the late stage of aging.After stimulation,we mainly analyzed the effects on early aging mice.We found that the effects of two types of t ES on behavior of different age mice were different.The tACS increased anxiety in young mice and decreased exploration ability in old mice in OPF.The results of Y-maze and new object recognition show that both types of t ES,especially tACS,can enhance memory in old mice,but not in young mice.The results of water maze showed there was no significant effect of both stimuli in two age groups.(2)For the AD mice model.The changes of indicators before and after stimulation were analyzed.Firstly,the analysis of the overall change of power spectrum shows that the effects of transcranial electrical stimulation on the EEG activities of Hip and PFC in different genotypes of mice are mainly reflected in the frequency band and had significant difference under task-state EEG paradigm.The effect of tDCS on WT mice is mainly in the high frequency band(Beta-Gamma;14-34 Hz),but it affects AD mice in all bands except theta.The effect of tACS on WT mice was mainly in the low frequency band(Delta-Theta;2-8 Hz),while the effect on AD mice was mainly in the high frequency band(Beta-Gamma;15-33 Hz).In addition,tDCS significantly reduced the full-band EEG activity of WT mice in spontaneous state.Movover,analysis of bands relative power in different frequency showed that the effects of the two stimuli were mainly reflected in Gamma power recorded by EEG in spontaneous state,and tDCS increased Gamma power of Hip in two kinds of mice,and tACS also enhanced Hip and PFC in AD mice.Task-state EEG records showed that the two stimuli enhanced theta or gamma of Hip and PFC in different mice,but decreased the other bands,and these changes were different in different genotypes of mice.Finally,the task-state paradigm downward behavior analysis showed that there was no significant difference between the two stimuli on Y-maze and OPF indicators in different genotypes of mice.Overall,the two stimuli had different effects on the number of mice explored new foreign arms in Y-maze,and tACS showed a certain enhancement effect.Conclusion:(1)tDCS and tACS can rehabilitate the cognitive ability of mice,especially tACS,to some extent in the early stage of aging.(2)the difference in the effects of tDCS and tACS on the EEG of Hip and PFC in AD and WT mice was mainly reflected in the changing frequency band,and the effects could be detected in the EEG recording mode of task state.(3)tDCS and tACS also have an effect on the relative power of EEG frequency band in mice,mainly by enhancing the Gamma power,which can be detected in the EEG recording mode of spontaneous state and task state,and there are differences in AD and WT mice.(4)tDCS and tACS have no significant difference in the influence on the behavioral indexes of AD and WT mice.Overall,tACS can promote the cognitive function of mice.