Home > Research > Publications & Outputs > Nanoformulated Bumetanide Ameliorates Social De...

Links

Text available via DOI:

View graph of relations

Nanoformulated Bumetanide Ameliorates Social Deficiency in BTBR Mice Model of Autism Spectrum Disorder

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published
  • Hui Lv
  • Xiao Gu
  • Xingyue Shan
  • Tailin Zhu
  • Bingke Ma
  • Hao-Tian Zhang
  • Victorio Bambini-Junior
  • Tiantian Zhang
  • Wei-Guang Li
  • Xiaoling Gao
  • Fei Li
Close
Article number870577
<mark>Journal publication date</mark>23/05/2022
<mark>Journal</mark>Frontiers in Immunology
Volume13
Number of pages13
Publication StatusPublished
<mark>Original language</mark>English

Abstract

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with few medication options. Bumetanide, an FDA-approved diuretic, has been proposed as a viable candidate to treat core symptoms of ASD, however, neither the brain region related to its effect nor the cell-specific mechanism(s) is clear. The availability of nanoparticles provides a viable way to identify pharmacological mechanisms for use in ASD. Here, we found that treatment with bumetanide, in a systemic and medial prefrontal cortex (mPFC) region-specific way, attenuated social deficits in BTBR mice. Furthermore, using poly (ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles [NP(bumetanide)], we showed that the administration of NP(bumetanide) in a mPFC region-specific way also alleviated the social deficits of BTBR mice. Mechanistically, the behavioral effect of NP(bumetanide) was dependent on selective microglia-specific targeting in the mPFC. Pharmacological depletion of microglia significantly reduced the effect of nanoencapsulation and depletion of microglia alone did not improve the social deficits in BTBR mice. These findings suggest the potential therapeutic capabilities of nanotechnology for ASD, as well as the relevant link between bumetanide and immune cells.