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The chemokine CCL2 protects against methylmercury neurotoxicity.: chemokines and methymercury neurotoxicity
- Source :
- Toxicological Sciences, vol. 125, no. 1, pp. 209-218, Review of Economic Dynamics, Review of Economic Dynamics, 2012, 125 (1), pp.209-18. ⟨10.1093/toxsci/kfr252⟩, Review of Economic Dynamics, Elsevier, 2012, 125 (1), pp.209-18. ⟨10.1093/toxsci/kfr252⟩
- Publication Year :
- 2011
- Publisher :
- Oxford University Press (OUP), 2011.
-
Abstract
- 10, 5 figures, 3 tables, 1 suppl figure and 1 suppl table; International audience; Industrial pollution due to heavy metals such as mercury is a major concern for the environment and public health. Mercury, in particular methylmercury (MeHg), primarily affects brain development and neuronal activity, resulting in neurotoxic effects. Because chemokines can modulate brain functions and are involved in neuroinflammatory and neurodegenerative diseases, we tested the possibility that the neurotoxic effect of MeHg may interfere with the chemokine CCL2. We have used an original protocol in young mice using a MeHg-contaminated fish-based diet for 3 months relevant to human MeHg contamination. We observed that MeHg induced in the mice cortex a decrease in CCL2 concentrations, neuronal cell death, and microglial activation. Knock-out (KO) CCL2 mice fed with a vegetal control food already presented a decrease in cortical neuronal cell density in comparison with wild-type animals under similar diet conditions, suggesting that the presence of CCL2 is required for normal neuronal survival. Moreover, KO CCL2 mice showed a pronounced neuronal cell death in response to MeHg. Using in vitro experiments on pure rat cortical neurons in culture, we observed by blockade of the CCL2/CCR2 neurotransmission an increased neuronal cell death in response to MeHg neurotoxicity. Furthermore, we showed that sod genes are upregulated in brain of wild-type mice fed with MeHg in contrast to KO CCL2 mice and that CCL2 can blunt in vitro the decrease in glutathione levels induced by MeHg. These original findings demonstrate that CCL2 may act as a neuroprotective alarm system in brain deficits due to MeHg intoxication.
- Subjects :
- MESH: Cell Death
Male
CCR2
Time Factors
MESH: Neurons
Cell Culture Techniques
microglia
Gene Expression
chemokines
Toxicology
MESH: Mice, Knockout
MESH: Dose-Response Relationship, Drug
Mice
0302 clinical medicine
methylmercury neurotoxicity
Premovement neuronal activity
MESH: Animals
Tissue Distribution
MESH: Superoxide Dismutase
Cells, Cultured
Chemokine CCL2
Mercury Poisoning, Nervous System
Mice, Knockout
Neurons
0303 health sciences
Cell Death
Microglia
Chemistry
Brain
Methylmercury Compounds
3. Good health
medicine.anatomical_structure
MESH: Environmental Pollutants
[SDV.TOX]Life Sciences [q-bio]/Toxicology
neuroprotection
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Environmental Pollutants
fish diet
Neuron death
MESH: Cells, Cultured
MESH: Methylmercury Compounds
medicine.medical_specialty
Programmed cell death
MESH: Gene Expression
Neurotransmission
Neuroprotection
MESH: Brain
03 medical and health sciences
neuronal cell death
MESH: Mice, Inbred C57BL
Internal medicine
medicine
Animals
MESH: Tissue Distribution
MESH: Mice
MESH: Chemokine CCL2
030304 developmental biology
MESH: Cell Culture Techniques
Dose-Response Relationship, Drug
Superoxide Dismutase
MESH: Mercury Poisoning, Nervous System
MESH: Time Factors
Neurotoxicity
CCL2/CCR2
medicine.disease
[SDE.ES]Environmental Sciences/Environmental and Society
MESH: Male
Mice, Inbred C57BL
Endocrinology
13. Climate action
Immunology
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10960929, 10966080, and 10942025
- Volume :
- 125
- Database :
- OpenAIRE
- Journal :
- Toxicological Sciences
- Accession number :
- edsair.doi.dedup.....216c6718ad5a68d2e915f60517ad6896
- Full Text :
- https://doi.org/10.1093/toxsci/kfr252