Long Term Music Increase Sensitivity Of Anti-Epileptic Drugs In Temporal Lobe Epilepsy

Epilepsy is one of the most common neurological disease,with the prevalence of 1%There are about 70 million epilepsy patients worldwide.Clinicians usually use anti-epileptic drugs(AEDs)to control seizures.Despite the existence of various AEDs with different mechanisms,epileptic patients still need life-long medication,the long-term and large-dose medicine will raise more economic concerns and unwanted side effects Therefore,it is urgent to find add-on therapies in epileptic research.At present,Mozart K.448(Mozart's Sonata for two pianos in D major,K.448)music therapy has shown therapeutic potential for neurological diseases including epilepsy and caught increasing attention.However,the characteristics and underlying mechanisms of music therapy are still unclear,needs further investigation.In this study,we investigated the therapeutic effect of Mozart K.448 music therapy and low-dose anti-epileptic drugs in mouse temporal lobe epilepsy models.We found that the 14 days long-term music therapy can increase the sensitivity of anti-epileptic drugs,which means that the generalized seizures of kindled mice can be controlled by low-dose sodium valproate or levetiracetam after receiving at least 12h daily music therapy lasting for 14 days.These mice are considered as the response(Res)group.While the generalized seizures of other mice cannot be controlled by low-dose AEDs even after receiving music,and these mice are considered as the non-response(Non)group.Even extending the music therapy could not show efficacy in Non group.Besides,only the whole Mozart K.448 is effective,the different isolated chapters of Mozart K.448 or other symphony had no similar effects.Further microdialysis and electrophysiology studies found that the long-term music could not raise the intracerebral AEDs' concentration but could directly inhibit the excitability of glutamatergic neurons in the primary auditory cortex in the response group.These results suggest that long-term music therapy can increase the sensitivity of AEDs in temporal lobe epilepsy,and may be a promising add-on therapy for temporal lobe epilepsy.