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Treating Depression with Ultrasound: An Exploratory Study

  • Author / Creator
    Guo, Huining
  • Depression is a common, recurrent and frequently chronic mental health disorder that has already become one of the leading health-care burdens. Despite the wide clinical application of antidepressants, a significant portion of patients does not benefit sufficiently from the standard medication therapies. Therefore, developing alternative safe and effective treatment options is required. Over the years, studies have shown that transcranial ultrasound has the ability to noninvasively and remotely modulate neurons and neural network activity. However, the prospect of using ultrasound as a treatment for depression still needs to be elucidated. The current study investigated the potential application of low-intensity pulsed ultrasound (LIPUS), a specific type of ultrasound, as a therapeutic option for depression. It was found that LIPUS stimulation significantly increased the viability of both neuron-like SH-SY5Y cells and primary glia cells in vitro. Further protein analysis revealed that LIPUS promoted the phosphorylation of β-catenin in primary glia cells and increased the level of brain-derived neurotrophic factor (BDNF) in both cell types. Animal studies using the repetitive restraint stress (RRS) model showed that LIPUS administration significantly alleviated the depression-like behaviors of mice in the sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST) and Y-maze test (YMT). Further testing indicated potential mechanisms for the beneficial effects of LIPUS on depression are associated with the promotion of neurogenesis and elevation of BDNF levels, which were consistent with the results of the in vitro study. The cuprizone (CPZ) induced demyelination animal model was used to determine the role of myelin and oligodendrocytes (OLs) both in pathogenesis and as therapeutic targets. It was found that LIPUS did not significantly attenuate the depressive-like behaviors in the TST, FST, and YMT in mice exposed to CPZ, although additional testing revealed that LIPUS alleviated CPZ-induced damage to both mature myelin and oligodendrocyte progenitor cells (OPCs). Taken together, the findings from the in vitro and in vivo studies indicate that LIPUS has potential as a promising therapeutic option for depression, not only by promoting neurogenesis and elevating BDNF levels, but also through protection and promotion of myelin and OLs. In addition to offering a new possible treatment for depression, this study also highlights the importance of neurogenesis and neurotrophy and the role of myelin and OLs in the pathogenesis of depression.

  • Subjects / Keywords
  • Graduation date
    2016-06
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R37D2QQ01
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.