Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus
Background: Chronic immunosuppressive treatment with cyclosporine A (CsA) leads to multiple side effects, including some that occur in the central nervous system (CNS). This study aims to investigate the impact of long-term CsA treatment on anxiety behavior and verify the alterations related to glut...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Affective Disorders Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666915322000865 |
| _version_ | 1811207771458109440 |
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| author | Marina Minto Cararo-Lopes Débora Guerini Souza Marcelo Ganzella Gisele Hansel Vanessa Kazlauckas Paloma Segura De Mello Larissa De Sá Lima Elisa Mitiko Kawamoto Luis Valmor Portela Diogo Onofre Souza Cristoforo Scavone Ana Elisa Böhmer |
| author_facet | Marina Minto Cararo-Lopes Débora Guerini Souza Marcelo Ganzella Gisele Hansel Vanessa Kazlauckas Paloma Segura De Mello Larissa De Sá Lima Elisa Mitiko Kawamoto Luis Valmor Portela Diogo Onofre Souza Cristoforo Scavone Ana Elisa Böhmer |
| author_sort | Marina Minto Cararo-Lopes |
| collection | DOAJ |
| description | Background: Chronic immunosuppressive treatment with cyclosporine A (CsA) leads to multiple side effects, including some that occur in the central nervous system (CNS). This study aims to investigate the impact of long-term CsA treatment on anxiety behavior and verify the alterations related to glutamate signaling in the rat hippocampus. Methods: Adult male Wistar rats were intraperitoneally injected with 15 mg/kg/day CsA for eight weeks, subjected to anxiety tests, and had their brains collected for biochemistry and Western blot analysis. Results: Herein, we reported that eight weeks of CsA treatment promoted an anxiety-like effect and increased N-methyl-D-aspartate receptor (NMDAR) GluN2 subunit levels, nitric oxide synthase, and cAMP-response element binding protein (CREB) activities. Limitations: Future work should consider the impact of long-term CsA treatment on NMDAR function, as well as on other neurotransmitter signaling pathways. Peripheral side effects should also be considered a factor that could lead to CsA-induced neuropsychiatric effects. Conclusions: In conclusion, this work reports modifications to CNS adaptive responses following chronic CsA treatment, which can influence anxiogenic behavior and other associated neurotoxic events. Understanding the mechanisms underlying CsA-induced neuropsychiatric side effects is an important step toward better symptom management in patients submitted to immunosuppression in the clinical setting. |
| first_indexed | 2024-04-12T04:10:26Z |
| format | Article |
| id | doaj.art-f99023825e4d4fe69ee5ec7611242149 |
| institution | Directory Open Access Journal |
| issn | 2666-9153 |
| language | English |
| last_indexed | 2024-04-12T04:10:26Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Affective Disorders Reports |
| spelling | doaj.art-f99023825e4d4fe69ee5ec76112421492022-12-22T03:48:31ZengElsevierJournal of Affective Disorders Reports2666-91532022-12-0110100394Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampusMarina Minto Cararo-Lopes0Débora Guerini Souza1Marcelo Ganzella2Gisele Hansel3Vanessa Kazlauckas4Paloma Segura De Mello5Larissa De Sá Lima6Elisa Mitiko Kawamoto7Luis Valmor Portela8Diogo Onofre Souza9Cristoforo Scavone10Ana Elisa Böhmer11Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo 05508-900, Brazil; Corresponding author.Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilNeurobiology Department, Max Planck Institute for Biophysical Chemistry, Göttingen, GermanyDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo 05508-900, BrazilDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo 05508-900, BrazilDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo 05508-900, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo 05508-900, BrazilDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo 05508-900, BrazilBackground: Chronic immunosuppressive treatment with cyclosporine A (CsA) leads to multiple side effects, including some that occur in the central nervous system (CNS). This study aims to investigate the impact of long-term CsA treatment on anxiety behavior and verify the alterations related to glutamate signaling in the rat hippocampus. Methods: Adult male Wistar rats were intraperitoneally injected with 15 mg/kg/day CsA for eight weeks, subjected to anxiety tests, and had their brains collected for biochemistry and Western blot analysis. Results: Herein, we reported that eight weeks of CsA treatment promoted an anxiety-like effect and increased N-methyl-D-aspartate receptor (NMDAR) GluN2 subunit levels, nitric oxide synthase, and cAMP-response element binding protein (CREB) activities. Limitations: Future work should consider the impact of long-term CsA treatment on NMDAR function, as well as on other neurotransmitter signaling pathways. Peripheral side effects should also be considered a factor that could lead to CsA-induced neuropsychiatric effects. Conclusions: In conclusion, this work reports modifications to CNS adaptive responses following chronic CsA treatment, which can influence anxiogenic behavior and other associated neurotoxic events. Understanding the mechanisms underlying CsA-induced neuropsychiatric side effects is an important step toward better symptom management in patients submitted to immunosuppression in the clinical setting.http://www.sciencedirect.com/science/article/pii/S2666915322000865CyclosporineAnxietyGlutamateN-methyl-D-aspartate receptorsCREBNitric oxide synthase |
| spellingShingle | Marina Minto Cararo-Lopes Débora Guerini Souza Marcelo Ganzella Gisele Hansel Vanessa Kazlauckas Paloma Segura De Mello Larissa De Sá Lima Elisa Mitiko Kawamoto Luis Valmor Portela Diogo Onofre Souza Cristoforo Scavone Ana Elisa Böhmer Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus Journal of Affective Disorders Reports Cyclosporine Anxiety Glutamate N-methyl-D-aspartate receptors CREB Nitric oxide synthase |
| title | Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus |
| title_full | Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus |
| title_fullStr | Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus |
| title_full_unstemmed | Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus |
| title_short | Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus |
| title_sort | long term cyclosporine a treatment promotes anxiety like behavior possible relation with glutamate signaling in rat hippocampus |
| topic | Cyclosporine Anxiety Glutamate N-methyl-D-aspartate receptors CREB Nitric oxide synthase |
| url | http://www.sciencedirect.com/science/article/pii/S2666915322000865 |
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