Publication date: Jul 21, 2025
Cadmium (Cd), a significant occupational and environmental pollutant, poses significant health risks due to its bioaccumulation and long biological half-life. Although Cd exposure has been identified as a risk factor for neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease, its specific effects on microglia-the resident immune cells of the central nervous system (CNS)-remain poorly understood. Here, we demonstrate that Cd exerts dual, dose-dependent effects on primary microglia. High doses (1-2 μM) triggered oxidative stress, apoptosis, and viability loss, whereas subtoxic doses (0. 125-0. 5 μM) enhanced phagocytic activity and ATP production. Notably, low-dose Cd elevated glutathione (GSH) levels, suggesting adaptive redox activation. Pretreatment with N-acetylcysteine (NAC) prevented high-dose Cd-induced cytotoxicity but suppressed the stimulatory effects of low-dose Cd on phagocytic activity and ATP production. Interestingly, NAC pretreatment paradoxically amplified phagocytosis at 1 μM Cd, despite partial ROS reduction. Collectively, our findings reveal that mild oxidative stress from low-dose Cd exposure promotes microglial phagocytosis via antioxidant responses, offering new insights into Cd’s neurotoxic mechanisms.
| Concepts | Keywords |
|---|---|
| Alzheimer | Cadmium |
| Atp | Cd |
| Cadmium | Dose |
| Environmental | Doses |
| Neurodegenerative | Dual |
| Exposure | |
| High | |
| Low | |
| Microglia | |
| Microglial | |
| Oxidative | |
| Phagocytic | |
| Phagocytosis | |
| Significant | |
| Stress |
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Cadmium |
| disease | MESH | neurodegenerative disorders |
| disease | MESH | Alzheimer’s disease |
| disease | MESH | Parkinson’s disease |
| disease | MESH | oxidative stress |
| pathway | REACTOME | Apoptosis |
| drug | DRUGBANK | ATP |
| drug | DRUGBANK | Glutathione |
| drug | DRUGBANK | Acetylcysteine |