Ambient PM_2.5 chronic exposure leads to cognitive decline in mice: From pulmonary to neuronal inflammation

Fine particulate matter 2.5 (PM_2.5), one of the main components of air pollutants, seriously threatens human health. Possible neuronal dysfunction induced by PM_2.5 has received extensive attention. However, there is little evidence for the specific biochemical mechanism of neuronal injury induced by PM_2.5. Moreover, the pathway for PM_2.5 transport from peripheral circulation to the central nervous system (CNS) is still unclear. In the current work, C57BL/6 mice were chronically exposed to ambient PM_2.5 for 3, 6, 9, and 12 months. Exposure to ambient PM_2.5 resulted in a significant reduction of cognitive ability in mice by Morris water maze test. PM_2.5 exposure induced a neuroinflammatory reaction after cognitive impairment, while inflammation in the hypothalamus and olfactory bulb tissue occurred earlier. The expression levels of integrity tight junction proteins in the blood-brain barrier (BBB) were reduced by PM_2.5 exposure. Pulmonary inflammation occurred much earlier and diminished at later stage of PM_2.5 exposure. The results indicated that chronic exposure to ambient PM_2.5 led to cognitive decline in mice; CNS dysfunction may be due to neuroinflammatory reactions; the reduced integrity of the BBB allowed the influence of pulmonary inflammation to neuronal alterations. The work may provide promising therapeutic or preventive targets for air pollution-induced neurodegenerative disease.