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Histamine H1 Receptors in Neural Stem Cells Are Required for the Promotion of Neurogenesis Conferred by H3 Receptor Antagonism following Traumatic Brain Injury.

Abstract
The neurological recovery following traumatic brain injury (TBI) is limited, largely due to a deficiency in neurogenesis. The present study explores the effects of histamine H3 receptor (H3R) antagonism on TBI and mechanisms related to neurogenesis. H3R antagonism or H3R gene knockout alleviated neurological injury in the late phase of TBI, and also promoted neuroblast differentiation to enhance neurogenesis through activation of the histaminergic system. Histamine H1 receptor, but not H2 receptor, in neural stem cells is shown to be essential for this promotion by using Hrh1fl/fl;NestinCreERT2 and Hrh2fl/fl;NestinCreERT2 mice. Moreover, increase in mature and functional neurons at the penumbra area conferred by H3R antagonism was abrogated in Hrh1fl/fl;NestinCreERT2 mice. Taken together, H3R antagonism provides neuroprotection against TBI in the late phase through the promotion of neurogenesis, and the H1 receptor in neural stem cells is required for this action. H3R may serve as a new target for clinical treatment of TBI.
AuthorsRujia Liao, Youchao Chen, Li Cheng, Lishi Fan, Han Chen, Yushan Wan, Yi You, Yanrong Zheng, Lei Jiang, Zhong Chen, Xiangnan Zhang, Weiwei Hu
JournalStem cell reports (Stem Cell Reports) Vol. 12 Issue 3 Pg. 532-544 (03 05 2019) ISSN: 2213-6711 [Electronic] United States
PMID30745032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Chemical References
  • Histamine Antagonists
  • Receptors, Histamine H1
  • Receptors, Histamine H3
Topics
  • Animals
  • Brain Injuries, Traumatic (drug therapy, metabolism)
  • Disease Models, Animal
  • Histamine Antagonists (pharmacology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells (drug effects, metabolism)
  • Neurogenesis (drug effects)
  • Neurons (drug effects, metabolism)
  • Receptors, Histamine H1 (metabolism)
  • Receptors, Histamine H3 (metabolism)

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