Abstract:
:Microglial activation is a key pathogenic process at the onset of Alzheimer's disease (AD). Identifying regulators of microglial activation bears great potential in elucidating causes and mechanisms of AD and determining candidates for early intervention. Previous studies demonstrate abnormal elevation of glutaminase C (GAC) in HIV-infected or immune-activated microglia. However, whether GAC elevation causes microglial activation remains unknown. In this study, we found heightened expression levels of GAC in early AD mouse brain tissues compared with those in control littermates. Investigations on an in vitro neuroinflammation model revealed that GAC is increased in primary mouse microglia following pro-inflammatory stimulation. To model GAC elevation we overexpressed GAC by plasmid transfection and observed that GAC-overexpression shift the microglial phenotype to a pro-inflammatory state. Treatment with BPTES, a glutaminase inhibitor, reversed LPS-induced microglial activation and inflammation. Furthermore, we discovered that GAC overexpression in mouse microglia increased exosome release and changed exosome content, which includes specific packaging of pro-inflammatory miRNAs that activate microglia. Together, our results demonstrate a causal effect of GAC elevation on microglial activation and exosome release, both of which promote the establishment of a pro-inflammatory microenvironment. Therefore, GAC may have important relevance to the pathogenesis of AD.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Gao G,Zhao S,Xia X,Li C,Li C,Ji C,Sheng S,Tang Y,Zhu J,Wang Y,Huang Y,Zheng JCdoi
10.3389/fncel.2019.00264subject
Has Abstractpub_date
2019-06-28 00:00:00pages
264issn
1662-5102journal_volume
13pub_type
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