PMID- 36994418
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230331
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 14
DP  - 2023
TI  - Cortex-specific transcriptome profiling reveals upregulation of 
      interferon-regulated genes after deeper cerebral hypoperfusion in mice.
PG  - 1056354
LID - 10.3389/fphys.2023.1056354 [doi]
LID - 1056354
AB  - Background: Chronic cerebral hypoperfusion (CCH) is commonly accompanied by brain 
      injury and glial activation. In addition to white matter lesions, the intensity 
      of CCH greatly affects the degree of gray matter damage. However, little is 
      understood about the underlying molecular mechanisms related to cortical lesions 
      and glial activation following hypoperfusion. Efforts to investigate the 
      relationship between neuropathological alternations and gene expression changes 
      support a role for identifying novel molecular pathways by transcriptomic 
      mechanisms. Methods: Chronic cerebral ischemic injury model was induced by the 
      bilateral carotid artery stenosis (BCAS) using 0.16/0.18 mm microcoils. Cerebral 
      blood flow (CBF) was evaluated using laser speckle contrast imaging (LSCI) 
      system. Spatial learning and memory were assessed by Morris water maze test. 
      Histological changes were evaluated by Hematoxylin staining. Microglial 
      activation and neuronal loss were further examined by immunofluorescence 
      staining. Cortex-specific gene expression profiling analysis was performed in 
      sham and BCAS mice, and then validated by quantitative RT-PCR and 
      immunohistochemistry (IHC). Results: In our study, compared with the sham group, 
      the right hemisphere CBF of BCAS mice decreased to 69% and the cognitive function 
      became impaired at 4 weeks postoperation. Besides, the BCAS mice displayed 
      profound gray matter damage, including atrophy and thinning of the cortex, 
      accompanied by neuronal loss and increased activated microglia. Gene set 
      enrichment analysis (GSEA) revealed that hypoperfusion-induced upregulated genes 
      were significantly enriched in the pathways of interferon (IFN)-regulated 
      signaling along with neuroinflammation signaling. Ingenuity pathway analysis 
      (IPA) predicted the importance of type I IFN signaling in regulating the CCH gene 
      network. The obtained RNA-seq data were validated by qRT-PCR in cerebral cortex, 
      showing consistency with the RNA-seq results. Also, IHC staining revealed 
      elevated expression of IFN-inducible protein in cerebral cortex following 
      BCAS-hypoperfusion. Conclusion: Overall, the activation of IFN-mediated signaling 
      enhanced our understanding of the neuroimmune responses induced by CCH. The 
      upregulation of IFN-regulated genes (IRGs) might exert a critical impact on the 
      progression of cerebral hypoperfusion. Our improved understanding of 
      cortex-specific transcriptional profiles will be helpful to explore potential 
      targets for CCH.
CI  - Copyright (c) 2023 Zhang, Guo, Tu, Yang, Li, Hu, Zhang, Jin and Hou.
FAU - Zhang, Zengyu
AU  - Zhang Z
AD  - Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai, 
      China.
FAU - Guo, Zimin
AU  - Guo Z
AD  - Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai, 
      China.
FAU - Tu, Zhilan
AU  - Tu Z
AD  - Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai, 
      China.
FAU - Yang, Hualan
AU  - Yang H
AD  - Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai, 
      China.
FAU - Li, Chao
AU  - Li C
AD  - School of Pharmacy, Hubei University of Science and Technology, Hubei, China.
FAU - Hu, Mengting
AU  - Hu M
AD  - Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai, 
      China.
FAU - Zhang, Yuan
AU  - Zhang Y
AD  - Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University, 
      Shanghai, China.
FAU - Jin, Pengpeng
AU  - Jin P
AD  - Department of Chronic Disease Management, Shanghai Pudong Hospital, Fudan 
      University, Shanghai, China.
FAU - Hou, Shuangxing
AU  - Hou S
AD  - Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230313
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC10040763
OTO - NOTNLM
OT  - RNA-seq
OT  - bilateral carotid artery stenosis
OT  - cerebral cortex
OT  - chronic cerebral hypoperfusion (CCH)
OT  - type I interferon
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/03/31 06:00
MHDA- 2023/03/31 06:01
PMCR- 2023/03/13
CRDT- 2023/03/30 03:04
PHST- 2022/09/28 00:00 [received]
PHST- 2023/02/24 00:00 [accepted]
PHST- 2023/03/31 06:01 [medline]
PHST- 2023/03/30 03:04 [entrez]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/13 00:00 [pmc-release]
AID - 1056354 [pii]
AID - 10.3389/fphys.2023.1056354 [doi]
PST - epublish
SO  - Front Physiol. 2023 Mar 13;14:1056354. doi: 10.3389/fphys.2023.1056354. 
      eCollection 2023.