Premium
Naloxone regulates the differentiation of neural stem cells via a receptor‐independent pathway
Author(s) -
Chen Jinlong,
Liang Lining,
Li Yuan,
Zhang Yixin,
Zhang Mengdan,
Yang Tingting,
Meng Fei,
Lai Xiaowei,
Li Changpeng,
He Jingcai,
He Meiai,
Xu Qiaoran,
Li Qian,
Law PingYee,
Loh Horace H.,
Pei Duanqing,
Sun Hao,
Zheng Hui
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902873r
Subject(s) - neural stem cell , (+) naloxone , microbiology and biotechnology , chemistry , receptor , neuroscience , stem cell , biology , opioid , biochemistry
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.