Cyclosporin A impairs neurogenesis and cognitive abilities in brain development via the IFN-γ-Shh-BDNF pathway
| Autor: | Hongyang Zhang, Fen He, Jiancong Sun, Ge Wang, Yuwei Zhang, Juntao Zou |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty medicine.drug_class Neurogenesis Immunology Hippocampus Hippocampal formation Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Neurotrophic factors GLI1 Cyclosporin a Internal medicine medicine Animals Immunology and Allergy Hedgehog Proteins Receptor Pharmacology biology Brain-Derived Neurotrophic Factor Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Animals Newborn 030220 oncology & carcinogenesis Cyclosporine biology.protein Cognition Disorders Immunosuppressive Agents Signal Transduction |
| Zdroj: | International Immunopharmacology. 96:107744 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2021.107744 |
| Popis: | A wealth of evidence indicate that the peripheral immune activation alters brain development. However, it is still largely unclear whether and how peripheral immunosuppression affects neurodevelopment. Here, we found that the immunosuppressant cyclosporin A (CsA) decreased the number of BrdU+, BrdU+/DCX+, BrdU+/NeuN + cells in the hippocampus, impaired learning and memory and inhibited protein levels of the shh signaling pathway, including Shh, Smo and Gli1. However, the shh pathway receptor agonist SAG could block the impairment of cognitive ability and the decrease of hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) level induced by CsA. We also found that CsA decreased the level of interferon-gamma (IFN-γ), while up-regulation of IFN-γ altered the inhibitory effect of the shh signaling pathway and the decrease of BDNF induced by CsA. Collectively, these data indicate that peripheral CsA impairs neurogenesis and cognition in brain development through downregulating the IFN-γ-Shh-BDNF pathway. The present study guides us to correctly apply immunomodulatory drugs in early life and suggests that the IFN-γ-Shh-BDNF pathway may represent a novel protective target for neurodevelopment under the condition of immunosuppression. |
| Databáze: | OpenAIRE |
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