2. Academic Validation
  3. Mixed Metal Components in PM2.5 Contribute to Chemokine Receptor CCR5-Mediated Neuroinflammation and Neuropathological Changes in the Mouse Olfactory Bulb

Mixed Metal Components in PM2.5 Contribute to Chemokine Receptor CCR5-Mediated Neuroinflammation and Neuropathological Changes in the Mouse Olfactory Bulb

  • Environ Sci Technol. 2024 Mar 4. doi: 10.1021/acs.est.3c08506.
Sheng Wei 1,  Ting Xu 1 2,  Nan Sang 3,  Huifeng Yue 3,  Yawen Chen 1 4,  Tao Jiang 5,  Tingwang Jiang 2,  Daqiang Yin 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
  • 2 Department of Key Laboratory, Changshu No.2 People's Hospital, Changshu 215500, China.
  • 3 College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan 030006, China.
  • 4 Postdoctoral Research Station of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
  • 5 Lyon Neuroscience Research Center (CRNL), Sensory Neuro-Ethology Team, 59 Bd Pinel, Bron 69500, France.
PMID: 38436231 DOI: 10.1021/acs.est.3c08506
Abstract

Particulate matter, especially PM2.5, can invade the central nervous system (CNS) via the olfactory pathway to induce neurotoxicity. The olfactory bulb (OB) is the key component integrating immunoprotection and olfaction processing and is necessarily involved in the relevant CNS health outcomes. Here we show that a microglial Chemokine Receptor, CCR5, is the target of environmentally relevant PM2.5 in the OB to trigger neuroinflammation and then neuropathological injuries. Mechanistically, PM2.5-induced CCR5 upregulation results in the pro-inflammatory paradigm of microglial activation, which subsequently activates TLR4-NF-κB neuroinflammation signaling and induces neuropathological changes that are closely related to neurodegenerative disorders (e.g., Aβ deposition and disruption of the blood-brain barrier). We specifically highlight that manganese and lead in PM2.5 are the main contributors to CCR5-mediated microglial activation and neuroinflammation in synergy with aluminum. Our results uncover a possible pathway of PM2.5-induced neuroinflammation and identify the principal neurotoxic components, which can provide new insight into efficiently diminishing the adverse health effects of PM2.5.

Keywords

CCR5; PM2.5; microglial activation; neuroinflammation; olfactory blub.

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