Gestational Exposure to Particulate Matter 2.5 (PM2.5) Leads to Spatial Memory Dysfunction and Neurodevelopmental Impairment in Hippocampus of Mice Offspring

Abstract

Prenatal exposure to air pollutants has long-term impact on growth retardation of nervous system development and is related to central nervous system diseases in children. However, it is not well-characterized whether gestational exposure to air pollutants affects the development of nervous system in offspring. Here, we investigated the effects of gestational exposure to particulate matter 2.5 (PM_2.5) on hippocampus development in mice offspring, through neurobehavioral, ultrastructural, biochemical and molecular investigations. We found that spatial memory in mice offspring from PM_2.5 high-dosage group was impaired. Next, hippocampal ultrastructure of the mice offspring in puberty exhibited mitochondrial damage related to PM_2.5 exposure. Interestingly, EdU-positive cells in the subgranular zone (SGZ) of offspring from PM_2.5 high-dosage group decreased, with NeuN⁺/EdU⁺cells reduced significantly. Furthermore, the numbers of NeuN⁺/TUNEL⁺, GFAP⁺/TUNEL⁺, and Iba1⁺/TUNEL⁺ double-labeled cells increased with PM_2.5 exposure in a dosage-dependent manner. In addition, gestational exposure to PM_2.5 resulted in increased levels of both mRNAs and proteins involved in apoptosis, including caspase-3, -8, -9, p53, and c-Fos, and decreased Bcl-2/Bax ratios in the hippocampus of mice offspring. Moreover, gestational exposure to PM_2.5 was dosage-dependently associated with the increased secretions of inflammatory proteins, including NF-κB, TNF-α, and IL-1β. Collectively, our results suggest that gestational exposure to PM_2.5 leads to spatial memory dysfunction and neurodevelopmental impairment by exerting effects on apoptotic and neuroinflammatory events, as well as the neurogenesis in hippocampus of mice offspring.