Toll-Like Receptor 5 Promotes the Neurogenesis From Embryonic Stem Cells and Adult Hippocampal Neural Stem Cells in Mice

Author:

Seong Kyung-Joo1,Choi Seungho1,Lee Hyun-Gwan2,Rhee Joon Haeng3,Lee Jin Ho4,Koh Jeong-Tae5,Kim Sun-Hun6,Choi Won-Seok4,Jung Ji-Yeon1,Kim Won-Jae1ORCID

Affiliation:

1. Dental Science Research Institute, Hard-tissue Biointerface Research Center, Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea

2. Department of Oceanography, Marine Ecological Disturbing and Harmful Organisms Research Center, BK21+ Climate Change and Coastal Ecosystem Prediction Research Center, Chonnam National University, Gwangju, Republic of Korea

3. National Research Laboratory of Molecular Microbial Pathogenesis, Research Institute of Vibrio Infection and Genome Research Center for Enteropathogenic Bacteria, Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea

4. School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea

5. Dental Science Research Institute, Hard-tissue Biointerface Research Center, Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea

6. Dental Science Research Institute, Hard-tissue Biointerface Research Center, Department of Oral Anatomy, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea

Abstract

Abstract Toll-like receptors (TLRs) make a crucial contribution to the innate immune response. TLR5 was expressed in embryoid body derived from mouse embryonic stem cells (mESCs) and βIII-tubulin-positive cells under all-trans retinoic acid-treated condition. TLR5 was upregulated during neural differentiation from mESCs and augmented the neural differentiation of mESCs via nuclear factor-κB and interleukin 6/CREB pathways. Besides, TLR5 was expressed in SOX2- or doublecortin-positive cells in the subgranular zone of the hippocampal dentate gyrus where adult neurogenesis occurs. TLR5 inhibited the proliferation of adult hippocampal neural stem cells (NSCs) by regulating the cell cycle and facilitated the neural differentiation from the adult hippocampal NSCs via JNK pathway. Also, TLR5 deficiency impaired fear memory performance in mice. Our data suggest that TLR5 is a crucial modulator of neurogenesis from mESCs and adult hippocampal NSCs in mice and represents a new therapeutic target in neurological disorders related to cognitive function.

Funder

National Research Foundation of Korea

Korean government

Chonnam National University Hospital Research Institute of Clinical Medicine

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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