|
Status |
Public on Feb 23, 2022 |
Title |
RNA Sequencing Facilitates Quantitative Analysis of Wild Type(MRL-mpj) and MRL-lpr (PBS or MSC treated) Hippocampoal Transcriptomes |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Complement cascades mediate synaptic pruning by microglia during early postnatal brain development. The process in NPSLE remains unclear. Here, we show that complement-coordinated elimination of synaptic terminals participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We elucidated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. Microglial engulfment of synapses explained behavioral disorders. We further determined that neuronal Nr4a1 signaling was essential for attracting C1q synaptic deposition then apposition of phagocytic microglia, ensuing synaptic loss and neurological disease. Minocycline-deactivated microglia, antibody-blocked C1q, or neuronal Nr4a1 restore protected lupus mice from synapse loss and NP manifestations. Our findings revealed an active role of neurons in coordinating microglia-mediated synaptic loss and highlight neuronal Nr4a1 and C1q as critical components amenable to pharmacological intervention.
|
|
|
Overall design |
RNA sequencing in hippocampus tissues from WT(MRL-mpj) mice and MRL-lpr mice with or without MSC(mesenchymal stem cell) administration, in triplicate.
|
|
|
Contributor(s) |
Han X, Sun L |
Citation(s) |
35177587 |
|
Submission date |
Jul 13, 2020 |
Last update date |
Feb 24, 2022 |
Contact name |
Han Xiaojuan |
E-mail(s) |
hxj_719@126.com
|
Phone |
15951950715
|
Organization name |
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
|
Street address |
Zhongshan Road 321
|
City |
Nanjing |
State/province |
Jiangsu |
ZIP/Postal code |
210008 |
Country |
China |
|
|
Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
Samples (9)
|
|
Relations |
BioProject |
PRJNA645810 |
SRA |
SRP271530 |