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Lead exposure induced microgliosis and astrogliosis in hippocampus of young mice potentially by triggering TLR4-MyD88-NFκB signaling cascades.
- Source :
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Toxicology letters [Toxicol Lett] 2015 Dec 03; Vol. 239 (2), pp. 97-107. Date of Electronic Publication: 2015 Sep 16. - Publication Year :
- 2015
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Abstract
- Proper proliferation and differentiation of neural stem cells or progenitors in hippocampus is critical to learn and memory functions, which might be disturbed by lead toxicity particularly in young individuals. While astroglial and microglial cells are known to play an important role in regulating neurogenesis of hippocampus, their abnormal response and influence on hippocampal neurogenesis remains unclear. In this study, therefore, glial response including microgliosis, astrogliogenesis and mediating involvement of TLR4-MyD88-NFκB signaling cascades were observed in hippocampus of young mice by animal model with lead (plumbum, Pb) exposure. It revealed that (1) significant microglial activation occurred in hippocampus soon following Pb exposure; (2) increased levels of TLR4, MyD88, NFκB expression were concomitantly detected; (3) BrdU-incorporated progenitor cells were observed in dentate gyrus with significantly-increased numbers at d28 in Pb insult group; (4) obvious astrogliogenesis was observed while these doublecortin-labeled differentiated neurons were not significantly changed in hippocampus; (5) administration of MyD88 inhibitory peptide attenuated or relieved above effects; (6) enhanced expression levels of IL-1β, TNFα, p38MAPK and ERK1/2 were also detected in hippocampus, indicating potential implication of inflammatory response and MAPK signaling activation in lead-induced microgliosis and astrogliosis. Data of this study overall have indicated that lead exposure could trigger or induce abnormal microgliosis and astrogliogenesis in the hippocampus of young mice through triggering TLR4-MyD88-NFκB signaling cascades, which might possibly thereafter disturb hippocampal neurogenesis and functional plasticity.<br /> (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Subjects :
- Aging
Animals
Astrocytes drug effects
Bromodeoxyuridine
Gene Expression Regulation
Hippocampus cytology
Mice
Mice, Inbred C57BL
Microglia drug effects
Myeloid Differentiation Factor 88 genetics
NF-kappa B genetics
Neurons drug effects
Neurons physiology
Toll-Like Receptor 4 genetics
Hippocampus drug effects
Lead toxicity
Myeloid Differentiation Factor 88 metabolism
NF-kappa B metabolism
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 239
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 26386401
- Full Text :
- https://doi.org/10.1016/j.toxlet.2015.09.015