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Updated: May 22, 2026
Sex Differences in Mouse Hippocampal Astrocytes after In-Vitro Ischemia
Published on: October 25, 2016
Variations in target gene expression and pathway profiles in the mouse hippocampus following treatment with different
Yinying Chen1, Caixiu Zhou, Yanan Yu
1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimen, Beijing 100700, China.
Abstract:
In order to elucidate the overlapping and diverse pharmacological protective mechanisms of different Chinese medicinal compounds, we investigated the alteration of gene expression and activation of signaling pathways in the mouse hippocampus after treatment of cerebral ischemia-reperfusion injury with various compounds. A microarray including 16,463 genes was used to identify differentially expressed genes among six treatment groups: baicalin (BA), jasminoidin (JA), cholic acid (CA), concha margaritiferausta (CM), sham, and vehicle. The US Food and Drug Administration (FDA) ArrayTrack system and Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to screen significantly altered genes and pathways (P < 0.05, fold change >1.5). Vehicle treatment alone resulted in alteration of 726 genes (283 upregulated, 443 downregulated) compared to the sham treatment group. BA, JA, and CA treatments, but not CM treatment, were effective in reducing infarct volume compared with vehicle treatment (P < 0.05). Compared with the CM group, a total of 167 (73 upregulated, 94 downregulated), 379 (211 upregulated, 168 downregulated), and 181 (76 upregulated, 105 downregulated) altered genes were found in the BA, JA, and CA groups, respectively. The numbers of overlapping genes between the BA and JA, BA and CA, and JA and CA groups were 28 (16 upregulated, 12 downregulated), 14 (4 upregulated, 10 downregulated), and 31 (8 upregulated, 23 downregulated), respectively. Three overlapping genes were identified among the BA, JA, and CA treatment groups: Il1rap, Gnb5, and Wdr38. Based on KEGG pathway analysis, two, seven, and four pathways were significantly activated in the BA, JA, and CA groups, respectively, when compared to the CM group. The ATP-binding cassette (ABC) transporters general pathway was activated by BA and JA treatment, and the mitogen-activated protein kinase (MAPK) signaling pathway was activated by JA and CA treatment. Alteration of IL-1 and Hspa1a expression was found by real time reverse transcription polymerase chain reaction, confirming the results of the microarray analysis. Our data demonstrated that polytypic profiles of 167-379 altered genes exist in the mouse hippocampus treated with different compounds known to be therapeutically effective in cerebral ischemia-reperfusion injury, and we were able to identify overlapping genes and pathways among these groups. Therefore, these different compounds may function through both overlapping and distinct pharmacological mechanisms to exert their therapeutic action.
Insights
Chinese medicinal compounds like baicalin, jasminoidin, and cholic acid protect against stroke by altering gene expression in the mouse hippocampus. These compounds show overlapping and distinct mechanisms, offering new therapeutic insights for cerebral ischemia-reperfusion injury.
Area of Science:
- Neuroscience
- Pharmacology
- Genomics
Background:
- Cerebral ischemia-reperfusion injury (CRI) poses a significant health challenge.
- Understanding the protective mechanisms of traditional Chinese medicines (TCMs) is crucial for developing novel therapies.
- Chinese medicinal compounds are known for their diverse pharmacological actions.
Purpose of the Study:
- To investigate the gene expression alterations and signaling pathway activations in the mouse hippocampus following CRI treatment with various TCMs.
- To elucidate the overlapping and distinct pharmacological protective mechanisms of different TCMs.
- To identify common and unique therapeutic targets for CRI.
Main Methods:
- Microarray analysis of 16,463 genes in mouse hippocampus after CRI.
- Treatment groups included baicalin (BA), jasminoidin (JA), cholic acid (CA), concha margaritiferausta (CM), sham, and vehicle.
- Analysis using FDA ArrayTrack and KEGG database to identify significantly altered genes and pathways (P < 0.05, fold change >1.5).
- Real-time reverse transcription polymerase chain reaction (RT-PCR) for validation.
Main Results:
- BA, JA, and CA treatments significantly reduced infarct volume compared to vehicle.
- Vehicle treatment altered 726 genes; BA, JA, and CA altered 167, 379, and 181 genes, respectively, compared to CM.
- Three overlapping genes (Il1rap, Gnb5, Wdr38) were identified among BA, JA, and CA treatments.
- Key pathways like ABC transporters and MAPK signaling were activated by specific treatments.
Conclusions:
- TCMs like BA, JA, and CA exhibit therapeutic effects in CRI by modulating gene expression in the hippocampus.
- These compounds exert their actions through both shared and unique pharmacological mechanisms.
- Identification of overlapping genes and pathways provides potential targets for CRI treatment development.
