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

Rujia Liao; Youchao Chen; Li Cheng; Lishi Fan; Han Chen; Yushan Wan; Yi You; Yanrong Zheng; Lei Jiang; Zhong Chen; Xiangnan Zhang; Weiwei Hu

doi:10.1016/j.stemcr.2019.01.004

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

Stem Cell Reports. 2019 Mar 5;12(3):532-544. doi: 10.1016/j.stemcr.2019.01.004. Epub 2019 Feb 7.

Authors

Rujia Liao¹, Youchao Chen¹, Li Cheng¹, Lishi Fan¹, Han Chen¹, Yushan Wan¹, Yi You¹, Yanrong Zheng¹, Lei Jiang¹, Zhong Chen¹, Xiangnan Zhang², Weiwei Hu³

Affiliations

¹ Department of Pharmacology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Basic Medical Science, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
² Department of Pharmacology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Basic Medical Science, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China. Electronic address: [email protected].
³ Department of Pharmacology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Basic Medical Science, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China; Pharmacy of Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China. Electronic address: [email protected].

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 Hrh1^fl/fl;Nestin^CreERT2 and Hrh2^fl/fl;Nestin^CreERT2 mice. Moreover, increase in mature and functional neurons at the penumbra area conferred by H3R antagonism was abrogated in Hrh1^fl/fl;Nestin^CreERT2 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.

Keywords: differentiation; histamine H1 receptor; histamine H3 receptor; neurogenesis; neuroprotection; traumatic brain injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Injuries, Traumatic / drug therapy*
Brain Injuries, Traumatic / metabolism
Disease Models, Animal
Histamine Antagonists / pharmacology*
Male
Mice
Mice, Inbred C57BL
Neural Stem Cells / drug effects*
Neural Stem Cells / metabolism*
Neurogenesis / drug effects*
Neurons / drug effects
Neurons / metabolism
Receptors, Histamine H1 / metabolism*
Receptors, Histamine H3 / metabolism*

Substances

Histamine Antagonists
Receptors, Histamine H1
Receptors, Histamine H3