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Ultrasound combined with glial cell line-derived neurotrophic factor-loaded microbubbles for the targeted treatment of drug addiction.
Wang, Feng; Wu, Hongwei; Hu, Azhen; Dong, Lei; Lin, Xiaoxia; Li, Menghao; Wang, Yongling; Li, Wenjun; Chang, Liansheng; Chang, Yuqiao; Liu, Hanqing; Shi, Yu; Li, Nana.
  • Wang F; Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Wu H; Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China.
  • Hu A; Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, China.
  • Dong L; Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
  • Lin X; Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Li M; Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Wang Y; Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Li W; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Chang L; Division of Oral and Craniofacial Biomedicine, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, United States.
  • Chang Y; Department of Human Anatomy Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Liu H; Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Shi Y; Central Laboratory, Shenzhen Samii Medical Center, Shenzhen, Guangdong, China.
  • Li N; Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China.
Front Bioeng Biotechnol ; 10: 961728, 2022.
Article in English | MEDLINE | ID: covidwho-2022647
ABSTRACT
Drug addiction is a serious problem globally, recently exacerbated by the COVID-19 pandemic. Glial cell-derived neurotrophic factor (GDNF) is considered a potentially effective strategy for the treatment of addiction. Previous animal experiments have proven that GDNF has a good therapeutic effect on drug addiction, but its clinical application is limited due to its poor blood-brain barrier (BBB) permeability. Low-frequency focused ultrasound, combined with microbubbles, is a non-invasive and reversible technique for locally-targeted BBB opening. In the present study, magnetic resonance imaging-guided low-frequency focused ultrasound, combined with GDNF microbubbles, was used to target BBB opening in the ventral tegmental area (VTA) region. The effects of GDNF on morphine-induced conditioned place preference (CPP) and acute withdrawal symptoms in rats after a partially opened BBB were evaluated by behavioral observation. Western blot was used to detect changes in tyrosine hydroxylase (TH) expression levels in the VTA region after different treatments, and high performance liquid chromatography was used to detect the changes in monoamine neurotransmitter content. The results showed that ultrasound combined with GDNF microbubbles targeted and opened the BBB in the VTA region, and significantly increased GDNF content, destroyed morphine-induced CPP, and reduced the withdrawal symptoms of morphine addiction in rats. Furthermore, the up-regulation of TH expression and the increase of norepinephrine and dopamine content induced by morphine were significantly reversed, and the increase of 5-hydroxytryptamine content was partially reversed. Therefore, ultrasound combined with GDNF microbubbles to target and open the BBB can effectively increase the content of central GDNF, thus playing a therapeutic role in morphine addiction. Our study provides a new approach to locally open the BBB and target delivery of neurotrophic factors, such as GDNF, to treat brain diseases like addiction.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Observational study / Prognostic study Language: English Journal: Front Bioeng Biotechnol Year: 2022 Document Type: Article Affiliation country: Fbioe.2022.961728

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Observational study / Prognostic study Language: English Journal: Front Bioeng Biotechnol Year: 2022 Document Type: Article Affiliation country: Fbioe.2022.961728