Role of Histamine H 3 Receptor Antagonist Pitolisant in Early Neural Differentiation of Mouse Embryonic Stem Cells.

التفاصيل البيبلوغرافية
العنوان:	Role of Histamine H 3 Receptor Antagonist Pitolisant in Early Neural Differentiation of Mouse Embryonic Stem Cells.
المؤلفون:	Xu G; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China., Liu N; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; Department of Clinical Pharmacy, Clinical Pharmacy Research Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Qiu Y; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China., Qi J; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China., Zhu D; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, China.
المصدر:	Stem cells and development [Stem Cells Dev] 2024 Feb; Vol. 33 (3-4), pp. 67-78. Date of Electronic Publication: 2024 Jan 08.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101197107 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-8534 (Electronic) Linking ISSN: 15473287 NLM ISO Abbreviation: Stem Cells Dev Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c2004-
مواضيع طبية MeSH:	Histamine/pharmacology , Receptors, Histamine H3/metabolism , Piperidines*, Mice ; Animals ; Mouse Embryonic Stem Cells/metabolism ; Histamine Agonists/pharmacology ; Histamine Agonists/therapeutic use
مستخلص:	The histamine H 3 receptor, prominently expressed in neurons with a minor presence in glial cells, acts as both an autoreceptor and an alloreceptor, controlling the release of histamine and other neurotransmitters. The receptor impacts various essential physiological processes. Our team's initial investigations had demonstrated that the histamine H 3 receptor antagonists could facilitate nerve regeneration by promoting the histamine H 1 receptors on primary neural stem cells (NSCs) in the traumatic brain injury mouse, which suggested the potential of histamine H 3 receptor as a promising target for treating neurological disorders and promoting nerve regeneration. Pitolisant (PITO) is the only histamine H 3 receptor antagonist approved by the Food and Drug Administration (FDA) for treating narcolepsy. However, there is no report on Pitolisant in neural development or regeneration, and it is urgent to be further studied in strong biological activity models in vitro. The embryonic stem (ES) cells were differentiated into neural cells in vitro, which replicated the neurodevelopmental processes that occur in vivo. It also provided an alternative model for studying neurodevelopmental processes and testing drugs for neurological conditions. Therefore, we aimed to elucidate the regulatory role of Pitolisant in the early differentiation of ES cells into neural cells. Our results demonstrated that Pitolisant could promote the differentiation of ES cells toward NSCs and stimulated the formation of growth cones. Furthermore, Pitolisant was capable of inducing the polarization of NSCs through the cAMP-LKB1-SAD/MARK2 pathway, but had no significant effect on later neuronal maturation. Pitolisant altered mitochondrial morphology and upregulated the levels of mitochondrion-related proteins TOM20, Drp1, and p-Drp1, and reversed the inhibitory effect of Mdivi-1 on mitochondrial fission during the early neural differentiation of ES cells. In addition, Pitolisant induced the increase in cytosolic Ca ²⁺ . Our study provided an experimental foundation for the potential application of histamine H 3 receptor-targeted modulators in the field of neuroregeneration.
فهرسة مساهمة:	Keywords: ES cells; Pitolisant; histamine H3 receptor; mitochondrial function; neural differentiation; neural stem cells
المشرفين على المادة:	820484N8I3 (Histamine) 4BC83L4PIY (pitolisant) 0 (Histamine Agonists) 0 (Receptors, Histamine H3) 0 (Piperidines)
تواريخ الأحداث:	Date Created: 20231130 Date Completed: 20240215 Latest Revision: 20240215
رمز التحديث:	20240215
DOI:	10.1089/scd.2023.0162
PMID:	38032751
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1557-8534
DOI:	10.1089/scd.2023.0162