Antidepressant-like Effect Of Low-intensity Transcranial Ultrasound Stimulation

Compared with TMS,tDCS and DBS,transcranial ultrasound stimulation(TUS)is a non-invasive neuromodulation technique with high spatial resolution and deep penetration depth and has gained increasing attention in recent years.We firstly applied optical intrinsic signal(OIS)imaging to study the whole process of neural activity in SD rats under TUS stimulation with different parameters.We found that the pulse repetition frequency(PRF)was a key parameter for effective brain stimulation by TUS.Inspired by clinical therapeutic of depression with transcranial magnetic stimulation(TMS),we then investigated the potential antidepressant-like effects of TUS in a rat model.We applied daily TUS for 2 weeks to the prelimbic cortex(PLC)of restraint depressed rats.Then we investigated both short-term(1 week after restraint)and long-term(3 weeks after restraint)effects of restraint and the antidepressant-like effects of TUS with a group of behavioral tests.In addition,we measured the hippocampal BDNF by western blotting to test the underlying mechanisms of antidepressant-like effects of TUS on depression,and also assessed the safety of long-term TUS by histologic analysis.The 48-hour-restraint stress could lead to long lasting reduction of exploratory behavior(1 week and 3 weeks after restraint)and protracted anhedonia(only observed 3 weeks after restraint).TUS application successfully reversed the depression-like phenotypes and promote the BDNF expression in left hippocampus.Our histologic results of H& E staining showed the safety of the TUS.These results proved that low intensity TUS had antidepressant-like effect and it could be a potential therapeutics of depression which are not responsive to current clinical treatments.