Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen-glucose deprivation.
Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.
1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|2 Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|3 Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yang
Y
Du
4 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Wenjun
W
Deng
5 Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zixing
Z
Wang
4 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
MingMing
M
Ning
1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|3 Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Wei
W
Zhang
2 Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Yiming
Y
Zhou
2 Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Eng H
EH
Lo
2 Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Changhong
C
Xing
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D018925:Chemokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose; D010100:Oxygen
Inflammation; human; mouse; oxygen–glucose deprivation; rat