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Toxicol Lett. 2019 Oct 10;314:106-116. doi: 10.1016/j.toxlet.2019.07.015. Epub 2019 Jul 12.

Early chronic low-level lead exposure reduced C-C chemokine receptor 7 in hippocampal microglia.

Author information

1
Dept of Psychology, The University of Texas at El Paso, El Paso, TX, USA; Dept of Psychology, Carleton College, Northfield, MN, USA. Electronic address: mflores@carleton.edu.
2
Dept of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA.
3
Dept of Public Health Sciences, The University of Texas at El Paso, El Paso, TX, USA; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.

Abstract

Chronic low-level lead exposure alters cognitive function in young children however the mechanisms mediating these deficits in the brain are not known. Previous studies in our laboratory showed that early lead exposure reduced the number of microglial cells in hippocampus/dentate gyrus of C57BL/6 J mice. In the current study, C-C chemokine receptor 7 (CCR7) and major histocompatibility complex II (MHC II) were examined to investigate whether these neuroimmune factors which are known to trigger cell migration and antigen presentation, were altered by early chronic lead exposure. Thirty-six C57BL/6 J male mice were exposed to 0 ppm (controls, n = 12), 30 ppm (low-dose, n = 12), or 430 ppm (higher-dose, n = 12) of lead acetate via dams' milk from postnatal day (PND) 0 to 28. Flow cytometry was used to quantify cell types and cell surface expression of MHC II and CCR7 in hippocampal and whole brain microglia. Non-parametric independent samples median tests were used to test for statistically significant differences between groups. As compared to controls, CCR7 in hippocampal microglia was decreased in the low-dose group, measured as geometric mean fluorescence intensity (GMFI); in the higher-dose group CCR7+MHC II- hippocampal microglia were decreased. Further analyses revealed that the higher-dose group had decreased percentage of CCR7+MHC II- hippocampal macrophages as compared to controls but increased MHC II levels in CCR7+MHC II+ hippocampal macrophages as compared to controls. It was also noted that lead exposure disrupted the balance of MHC II and/or CCR7 in lead exposed animals. Reduced CCR7 in hippocampal microglia might alter the neuroimmune environment in hippocampi of lead exposed animals. Additional studies are needed to test this possibility.

KEYWORDS:

CCR7; Flow cytometry; Lead; MHC II; Microglia

PMID:
31306743
DOI:
10.1016/j.toxlet.2019.07.015
[Indexed for MEDLINE]

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