Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice
Abstract Background We examined chronic gadolinium retention impact on gene expression in the mouse central nervous system (CNS) after injection of linear or macrocyclic gadolinium-based contrast agents (GBCAs). Methods From 05/2022 to 07/2023, 36 female mice underwent weekly intraperitoneal injecti...
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SpringerOpen
2025-01-01
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| Series: | European Radiology Experimental |
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| Online Access: | https://doi.org/10.1186/s41747-024-00546-x |
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| author | Chuanbing Wang Yuxia Tang Jiajia Tang Jie Zhang Siqi Wang Feiyun Wu Shouju Wang |
| author_facet | Chuanbing Wang Yuxia Tang Jiajia Tang Jie Zhang Siqi Wang Feiyun Wu Shouju Wang |
| author_sort | Chuanbing Wang |
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| description | Abstract Background We examined chronic gadolinium retention impact on gene expression in the mouse central nervous system (CNS) after injection of linear or macrocyclic gadolinium-based contrast agents (GBCAs). Methods From 05/2022 to 07/2023, 36 female mice underwent weekly intraperitoneal injections of gadodiamide (2.5 mmol/kg, linear), gadobutrol (2.5 mmol/kg, macrocyclic), or saline. Mice were sacrificed on day 29 or 391 after a 1-year washout. Assessments included magnetic resonance imaging (MRI), mechanical hyperalgesia tests, and inductively coupled plasma mass spectrometry to measure gadolinium levels. Ribonucleic acid (RNA) sequencing and bioinformatic analyses identified differentially expressed genes (DEGs), with validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). Results Post-gadodiamide, MRI showed increased signal intensity in the deep cerebellar nuclei (pre, 0.997 ± 0.006 versus post, 1.086 ± 0.013, p < 0.001). Mechanical hyperalgesia tests indicated transient sensory changes. After 1-year, gadolinium retention was noted in the brain (5.92 ± 0.32 nmol/kg) and spinal cord (1.23 ± 0.66 nmol/kg) with gadodiamide, compared to saline controls (0.06 ± 0.02 nmol/kg in brains and 0.28 ± 0.06 nmol/kg in spinal cords). RNA sequencing identified 17 shared DEGs between brain and spinal cord in the gadodiamide group on day 391, with altered Hmgb2 and Sgk1 expression confirmed by qRT-PCR and WB. Reactome pathway analysis showed enrichment in neuroinflammation pathways. No DEGs were detected in brains on day 29. Conclusion Chronic gadolinium deposition from repeated linear GBCA but not macrocyclic administration causes significant gene expression alterations in the mouse CNS, particularly affecting neuroinflammation pathways. Relevance statement This study examined the long-term impact of chronic gadolinium retention on gene expression in the mouse CNS, uncovering significant changes associated with neuroinflammation pathways after repeated administration of linear GBCA, but not with macrocyclic GBCA. These findings highlight the importance of further research on the long-term safety of linear GBCA in medical imaging. Key Points Chronic gadolinium retention alters gene expression in the mouse central nervous system. Significant neuroinflammatory pathway changes were observed after linear gadodiamide exposure. MRI showed increased signal intensity in deep cerebellar nuclei after gadodiamide injection. Graphical Abstract |
| format | Article |
| id | doaj-art-8e44b12eca364c9388d2030babe8c3d2 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | European Radiology Experimental |
| spelling | doaj-art-8e44b12eca364c9388d2030babe8c3d22025-01-12T12:07:26ZengSpringerOpenEuropean Radiology Experimental2509-92802025-01-019111110.1186/s41747-024-00546-xLong-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of miceChuanbing Wang0Yuxia Tang1Jiajia Tang2Jie Zhang3Siqi Wang4Feiyun Wu5Shouju Wang6Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background We examined chronic gadolinium retention impact on gene expression in the mouse central nervous system (CNS) after injection of linear or macrocyclic gadolinium-based contrast agents (GBCAs). Methods From 05/2022 to 07/2023, 36 female mice underwent weekly intraperitoneal injections of gadodiamide (2.5 mmol/kg, linear), gadobutrol (2.5 mmol/kg, macrocyclic), or saline. Mice were sacrificed on day 29 or 391 after a 1-year washout. Assessments included magnetic resonance imaging (MRI), mechanical hyperalgesia tests, and inductively coupled plasma mass spectrometry to measure gadolinium levels. Ribonucleic acid (RNA) sequencing and bioinformatic analyses identified differentially expressed genes (DEGs), with validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). Results Post-gadodiamide, MRI showed increased signal intensity in the deep cerebellar nuclei (pre, 0.997 ± 0.006 versus post, 1.086 ± 0.013, p < 0.001). Mechanical hyperalgesia tests indicated transient sensory changes. After 1-year, gadolinium retention was noted in the brain (5.92 ± 0.32 nmol/kg) and spinal cord (1.23 ± 0.66 nmol/kg) with gadodiamide, compared to saline controls (0.06 ± 0.02 nmol/kg in brains and 0.28 ± 0.06 nmol/kg in spinal cords). RNA sequencing identified 17 shared DEGs between brain and spinal cord in the gadodiamide group on day 391, with altered Hmgb2 and Sgk1 expression confirmed by qRT-PCR and WB. Reactome pathway analysis showed enrichment in neuroinflammation pathways. No DEGs were detected in brains on day 29. Conclusion Chronic gadolinium deposition from repeated linear GBCA but not macrocyclic administration causes significant gene expression alterations in the mouse CNS, particularly affecting neuroinflammation pathways. Relevance statement This study examined the long-term impact of chronic gadolinium retention on gene expression in the mouse CNS, uncovering significant changes associated with neuroinflammation pathways after repeated administration of linear GBCA, but not with macrocyclic GBCA. These findings highlight the importance of further research on the long-term safety of linear GBCA in medical imaging. Key Points Chronic gadolinium retention alters gene expression in the mouse central nervous system. Significant neuroinflammatory pathway changes were observed after linear gadodiamide exposure. MRI showed increased signal intensity in deep cerebellar nuclei after gadodiamide injection. Graphical Abstracthttps://doi.org/10.1186/s41747-024-00546-xAnimalsCentral nervous systemContrast mediaGadoliniumGene expression |
| spellingShingle | Chuanbing Wang Yuxia Tang Jiajia Tang Jie Zhang Siqi Wang Feiyun Wu Shouju Wang Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice European Radiology Experimental Animals Central nervous system Contrast media Gadolinium Gene expression |
| title | Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice |
| title_full | Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice |
| title_fullStr | Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice |
| title_full_unstemmed | Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice |
| title_short | Long-term effects of linear versus macrocyclic GBCAs on gene expression in the central nervous system of mice |
| title_sort | long term effects of linear versus macrocyclic gbcas on gene expression in the central nervous system of mice |
| topic | Animals Central nervous system Contrast media Gadolinium Gene expression |
| url | https://doi.org/10.1186/s41747-024-00546-x |
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