1. Academic Validation
  2. Role of PKA/CREB/BDNF signaling in PM2.5-induced neurodevelopmental damage to the hippocampal neurons of rats

Role of PKA/CREB/BDNF signaling in PM2.5-induced neurodevelopmental damage to the hippocampal neurons of rats

  • Ecotoxicol Environ Saf. 2021 May;214:112005. doi: 10.1016/j.ecoenv.2021.112005.
Jie Liu 1 Benke Liu 1 Ping Yuan 1 Li Cheng 1 Hong Sun 1 Jianxiong Gui 1 Yanan Pan 1 Dishu Huang 1 Hengsheng Chen 1 Li Jiang 2
Affiliations

Affiliations

  • 1 Department of Neurology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, 136# Zhongshan 2nd Road, Chongqing 400014, China.
  • 2 Department of Neurology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, 136# Zhongshan 2nd Road, Chongqing 400014, China. Electronic address: ljiang@hospital.cqmu.edu.cn.
Abstract

Exposure to fine particulate matter (PM2.5) is implicated in neurodevelopmental disorders including cognitive decline, attention-deficit/hyperactivity disorder, and autism spectrum disorder. However, the specific molecular mechanisms by which PM2.5 impacts neurodevelopment are poorly understood. Accordingly, in the present study, the role of protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling in PM2.5-induced neurodevelopmental damage was investigated using primary cultured hippocampal neurons. When hippocampal neurons cultured for 3 days in vitro (DIV3) were exposed to PM2.5 for 24 h and 96 h, neuronal viability decreased by 18.8% and 32.7% respectively, percentage of TUNEL-positive neurons increased by 78.5% and 64.0% separately, caspase-9 expression increased, lower postsynaptic density and shorter active zones were observed by transmission electron microscopy, expression of synapse-related proteins including postsynaptic density-95 (PSD95), growth associated protein-43 (GAP43), and synaptophysin (SYP) were decreased, and the phosphorylation levels of PKA, CREB, and BDNF expression also decreased. However, the PM2.5-induced neuronal damage could be ameliorated or aggravated to varying degrees by up- or down-regulation of the PKA/CREB/BDNF signaling pathway, respectively. Our results indicate that PM2.5 exposure exerts neurodevelopmental toxicity as indicated by lower viability, Apoptosis, and synaptic damage in primary cultured hippocampal neurons, and that the PKA/CREB/BDNF pathways could play a vital role in PM2.5-mediated neurodevelopmental toxicity.

Keywords

Fine particulate matter; Hippocampal neuron; PKA/CREB/BDNF; Synapse.

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