Neurodevelopmental toxicity induced by maternal PM2.5 exposure and protective effects of quercetin and Vitamin C

• Published in: Chemosphere (Oxford) 2018-12, Vol.213, p.182-196
• Main Authors: Zhang, Minjia, Liu, Wei, Zhou, Yalin, Li, Yong, Qin, Yong, Xu, Yajun
• Format: Article
• Language: English
• Subjects: Animals; Ascorbic Acid - chemistry; Female; Male; Maternal Exposure; Mice; Neurodevelopmental Disorders - chemically induced; Neurodevelopmental Disorders - pathology; Neurodevelopmental toxicity; PM2.5; Pregnancy; Quercetin; Quercetin - chemistry; Vitamin C
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2018.09.009

Epidemiological studies show that maternal exposure to PM2.5 affects the neurodevelopment of the offspring, especially the neurocognitive function. However, no relevant experimental researches have been published on toxic mechanism and diet intervention. We evaluated the effects of exposure to different doses of PM2.5 on the behavioral development of offspring via a PM2.5 exposure model established by intratracheal instillation, explored its mechanism and the protective effects of quercetin and VC intervention, and focused on the protein expression of CREB/BDNF signaling pathway. Specifically, Exposure to PM2.5 during gestation and lactation period caused maternal oxidative stress. Maternal exposure to PM2.5 changed postnatal open-field behaviors in both gender, impaired spatial learning and memory in the female offspring, increased the level of IL-1β, IL-6, down-regulated p-CREB/CREB, BDNF, TrkB, p-CaMKII/CaMKII, p-CaMKIV/CaMKIV, up-regulated p-Akt/Akt and p-ERK1/2/ERK1/2 in the offspring. In addition, maternal supplementation with quercetin ameliorate the maternal oxidative stress, improved progeny inflammatory response, regulated BDNF, TrkB, p-Akt/Akt, p-ERK1/2/ERK1/2 in female offspring, regulated TrkB, p-CREB/CREB and p-Akt/Akt in male offspring. Maternal supplementation with VC increased the levels of CAT in maternal mice, up-regulated BDNF in female offspring, regulated p-CREB/CREB and p-ERK1/2/ERK1/2 in male offspring. Our findings indicate that PM2.5 exposure during pregnancy and lactation could impair behavioral development of offspring. Quercetin shows more protective effects than VC. The mechanism of neurodevelopmental toxicity induced by PM2.5 may be related to oxidative stress, inflammatory response and modulation of the CREB/BDNF signaling pathway. •PM2.5 exposure caused maternal oxidative stress.•PM2.5 changed postnatal open-field behaviors in both gender and impaired spatial learning and memory in the female.•PM2.5 increased the level of IL-1β, IL-6, down-regulated p-CREB/CREB, BDNF, TrkB, p-CaMKII/CaMKII, p-CaMKIV/CaMKIV, upregulated p-Akt/Akt and p-ERK1/2/ERK1/2 in the offspring.•Quercetin and VC showed some protective effects.