Diagenode

Neutral sphingomyelinase 2 inhibition attenuates extracellular vesiclerelease and improves neurobehavioral deficits in murine HIV.


Zhu X. et al.

People living with HIV (PLH) have significantly higher rates of cognitive impairment (CI) and major depressive disorder (MDD) versus the general population. The enzyme neutral sphingomyelinase 2 (nSMase2) is involved in the biogenesis of ceramide and extracellular vesicles (EVs), both of which are dysregulated in PLH, CI, and MDD. Here we evaluated EcoHIV-infected mice for behavioral abnormalities relevant to depression and cognition deficits, and assessed the behavioral and biochemical effects of nSMase2 inhibition. Mice were infected with EcoHIV and daily treatment with either vehicle or the nSMase2 inhibitor (R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)-carbamate (PDDC) began 3 weeks post-infection. After 2 weeks of treatment, mice were subjected to behavior tests. EcoHIV-infected mice exhibited behavioral abnormalities relevant to MDD and CI that were reversed by PDDC treatment. EcoHIV infection significantly increased cortical brain nSMase2 activity, resulting in trend changes in sphingomyelin and ceramide levels that were normalized by PDDC treatment. EcoHIV-infected mice also exhibited increased levels of brain-derived EVs and altered microRNA cargo, including miR-183-5p, miR-200c-3p, miR-200b-3p, and miR-429-3p, known to be associated with MDD and CI; all were normalized by PDDC. In conclusion, inhibition of nSMase2 represents a possible new therapeutic strategy for the treatment of HIV-associated CI and MDD.

Tags
D-Plex small RNA-seq

Share this article

Published
July, 2022

Source

Products used in this publication

  • Small RNA library preparation with UMI for Illumina
    C05030001
    D-Plex Small RNA-seq Library Prep Kit x24
  • Illumina index primers for D-Plex small RNA library preparation with UMI
    C05030010
    D-Plex 24 Single Indexes for Illumina - Set #A

イベント

  • Symposium of the Young Scientist Association
    Vienna, Austria
    May 28-May 29, 2024
  • ESHG 2024
    Berlin, Germany
    Jun 1-Jun 4, 2024
  • CLEPIC 2024
    Warsaw, Poland
    Jun 5-Jun 7, 2024
  • EACR 2024
    Rotterdam, Netherlands
    Jun 10-Jun 13, 2024
  • Chromatin meets South 2024
    Marseille, France
    Jun 13-Jun 14, 2024
 すべてのイベントを見る

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics