Naloxone regulates the differentiation of neural stem cells via a receptor‐independent pathway
| Autor: | Qiaoran Xu, Duanqing Pei, Jingcai He, Yixin Zhang, Tingting Yang, Jinlong Chen, Hui Zheng, Lining Liang, Xiaowei Lai, Mengdan Zhang, Ping-Yee Law, Changpeng Li, Qian Li, Meiai He, Yuan Li, Horace H. Loh, Hao Sun, Fei Meng |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Narcotics 0301 basic medicine Narcotic Antagonists Neurogenesis Receptors Opioid mu Chromosomal translocation (+)-Naloxone Pharmacology Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Genetics medicine Animals Receptor Molecular Biology Endogenous opioid Mice Knockout Morphine Naloxone Chemistry Cell Differentiation Fibroblasts Embryo Mammalian Neural stem cell Mice Inbred C57BL 030104 developmental biology nervous system Opioid Female 030217 neurology & neurosurgery Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 34:5917-5930 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201902873r |
| Popis: | The abilities of opioids to activate downstream signaling pathways normally depend on the binding between opioids and their receptors. However, opioids may also function in a receptor-independent manner, especially in neural stem cells (NSCs) in which the expression of opioid receptors and endogenous opioid agonists is low. When two opioids, morphine and naloxone, were used during the early stage of NSC differentiation, increased neurogenesis was observed. However, naloxone methiodide, a membrane impenetrable analog of naloxone, did not affect the NSC differentiation. The abilities of morphine and naloxone to facilitate neurogenesis were also observed in opioid receptor-knockout NSCs. Therefore, morphine and naloxone promote neurogenesis in a receptor-independent manner at least during the early stage. In addition, the receptor-independent functions of opioids were not observed in methylcytosine dioxygenase ten-eleven translocation 1 (Tet1) knockout NSCs. When the expression of opioid receptors increased and the expression of Tet1 decreased during the late stage of NSC differentiation, morphine, but not naloxone, inhibited neurogenesis via traditional receptor-dependent and miR181a-Prox1-Notch-related pathway. In summary, the current results demonstrated the time-dependent effects of opioids during the differentiation of NSCs and provided additional insight on the complex functions of opioids. |
| Databáze: | OpenAIRE |
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