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

Area of Science:

• Neuroscience
• Immunology
• Toxicology

Background:

• Chronic low-level lead exposure is known to impair cognitive function in children.
• The precise brain mechanisms underlying lead-induced cognitive deficits remain unclear.
• Previous research indicated lead exposure reduces microglial cell numbers in the hippocampus.

Purpose of the Study:

• To investigate the impact of early chronic lead exposure on neuroimmune factors C-C chemokine receptor 7 (CCR7) and major histocompatibility complex II (MHC II) in mice.
• To determine if lead exposure alters CCR7 and MHC II expression in hippocampal microglia, potentially affecting cell migration and antigen presentation.

Main Methods:

• C57BL/6J mice were exposed to lead acetate (0, 30, or 430 ppm) via maternal milk from postnatal day 0 to 28.
• Flow cytometry was employed to quantify microglial cell types and surface expression of CCR7 and MHC II in hippocampal and whole brain samples.
• Statistical analysis utilized non-parametric independent samples median tests to compare groups.

Main Results:

• Low-dose lead exposure decreased CCR7 geometric mean fluorescence intensity in hippocampal microglia compared to controls.
• Higher-dose lead exposure reduced CCR7+MHC II- hippocampal microglia and the percentage of CCR7+MHC II- hippocampal macrophages.
• Lead exposure altered MHC II levels in CCR7+MHC II+ hippocampal macrophages and disrupted the overall balance of MHC II and CCR7 in lead-exposed animals.

Conclusions:

• Early chronic lead exposure significantly alters CCR7 and MHC II expression in hippocampal microglia and macrophages.
• Reduced CCR7 in hippocampal microglia may contribute to neuroimmune dysregulation in the hippocampus following lead exposure.
• These findings highlight potential mechanisms by which lead impacts brain development and cognitive function, warranting further investigation.