Transcranial Ultrasound Stimulation Reverses Behavior Changes and the Expression of Calcium-Binding Protein in a Rodent Model of Schizophrenia.

ABSTRACT

Cognitive dysfunctions are a core feature of schizophrenia that may be linked to abnormalities in gamma-aminobutyric-acid (GABA)ergic neurons. Traditional antipsychotics show poor efficacy in treating cognitive symptoms. The purpose of this study was to investigate the restorative role of transcranial ultrasound stimulation (TUS) in counteracting dizocilpine (MK-801)-induced cognitive deficits and GABAergic interneuron dysfunction in a simulation of schizophrenia. Some rats subjected to MK-801 administration were treated with low-intensity pulsed ultrasound (LIPUS) daily for 5 days, while other rats subjected to MK-801 administration received no LIPUS treatment. After LIPUS treatment, the neuroprotective effects of LIPUS in the LIPUS-treated rats were assessed through behavioral analysis, western blotting, and histological observations. Compared with the MK-801-treated group, the MK-801 plus LIPUS-treated rats revealed a preference for novel objects. The MK-801 plus LIPUS-treated rats also exhibited a significant decrease in swim times compared to the MK-801-treated rats. LIPUS stimulation significantly increased hippocampal levels of CB and PV and restored the cell densities of PV + and CB + in the cingulate cortex in the MK-801 plus LIPUS-treated group. In addition, LIPUS stimulation rebalanced the BDNF levels in the hippocampus and medial prefrontal cortex. Our findings indicate that LIPUS improves cognitive deficits and ameliorates neuropathology in MK-801-treated rats. These results suggest that LIPUS may constitute a potential novel therapeutic approach for the treatment of schizophrenia.