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Toll-like receptor 4 differentially regulates adult hippocampal neurogenesis in an age- and sex-dependent manner.

Authors
  • Connolly, Meghan G1
  • Yost, Oriana L1
  • Potter, Opal V2
  • Giedraitis, Megan E1
  • Kohman, Rachel A1
  • 1 Department of Psychology, University of North Carolina Wilmington, Wilmington, North Carolina, USA.
  • 2 School of Medicine, Wake Forest University, Winston Salem, North Carolina, USA.
Type
Published Article
Journal
Hippocampus
Publisher
Wiley (John Wiley & Sons)
Publication Date
Sep 01, 2020
Volume
30
Issue
9
Pages
958–969
Identifiers
DOI: 10.1002/hipo.23209
PMID: 32343455
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Toll-like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with normal aging is currently unknown. The present study evaluated whether TLR4 deficiency alters adult hippocampal neurogenesis in young (3-4 months) and aged (18-20 months), male and female, TLR4 deficient (TLR4-/-; B6.B10ScN-Tlr4lps-del/JthJ) and wild type (WT) mice. Additionally, neurogenesis within the dorsal and the ventral hippocampal subdivisions was evaluated to determine if TLR4 has differential effects across the hippocampus. Bromodeoxyuridine (BrdU) was administered to quantify new cell survival as well as cell differentiation. Ki-67 was measured to evaluate cell proliferation. Results show that young TLR4-/- females had higher rates of proliferation and neuronal differentiation in both the dorsal and ventral hippocampus relative to WT females. Young TLR4-/- males show elevated proliferation and neuronal differentiation mainly in the ventral hippocampus. While young TLR4-/- mice show enhanced neurogenesis compared to young WT mice, the increase was not apparent in the aged TLR4-/- mice. Both aged WT and TLR4-/- mice showed a decrease in proliferation, new cell survival, and neuronal differentiation compared to young WT and TLR4-/- mice. The data collectively indicate that TLR4 regulates hippocampal neurogenesis in young adults, but that these effects are region-specific in males and that females show broader changes in neurogenesis throughout the hippocampus. © 2020 Wiley Periodicals, Inc.

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