Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Brain Behav. 2019 Dec;9(12):e01453. doi: 10.1002/brb3.1453. Epub 2019 Nov 11.
Fine particulate matter (PM2.5) is closely associated with many neurological disorders including neurodegenerative disease, stroke, and brain tumors. However, the toxic effects of PM2.5 on neurodevelopment remain unclear. In this study, we aimed to determine the neurotoxic effects of early postnatal exposure to PM2.5 in immature and mature rats.
We exposed neonatal rats to PM2.5 (2 or 10 mg/kg body weight) through intranasal instillation from postnatal day (PND) 3-15, once a day. Emotional and cognitive development were evaluated using the elevated plus maze, forced swimming, and Morris water maze tests. Hippocampal tissue was collected and subjected to transmission electron microscopy observation and western blot analysis.
Rats had lower body weight after exposure to high dose of PM2.5. The behavioral test results indicated that high-dose PM2.5 exposure led to increased anxiety-like symptoms in immature and mature rats, apparent depressive-like behaviors in mature rats, and impaired spatial learning and memory abilities in immature rats, and low-dose PM2.5 exposure increased anxiety-like behaviors in immature rats. Further, high-dose PM2.5 exposure contributed to fewer synapses, thinner postsynaptic density, and shorter active zone in immature and mature rats, and also decreased expressions of synaptophysin (SYP), growth associated protein-43 (GAP43), and postsynaptic density-95 (PSD95) in immature rats, SYP and PSD95 in mature rats. Moreover, low-dose PM2.5 exposure diminished the expression of PSD95 in immature rats. In addition, high-dose PM2.5 exposure reduced brain-derived neurotrophic factor (BDNF) expression and cAMP response element binding protein (CREB) phosphorylation in both immature and mature rats, and low-dose PM2.5 exposure lessened BDNF expression and CREB phosphorylation in immature rats.
Our findings indicate that PM2.5 impairs emotional and cognitive development by disrupting structural synaptic plasticity, possibly via the CREB/BDNF signaling pathway.
细颗粒物（PM2.5）与许多神经退行性疾病有关，包括神经退行性疾病、中风和脑肿瘤。然而，PM2.5 对神经发育的毒性作用尚不清楚。在这项研究中，我们旨在确定早期产后暴露于 PM2.5 对未成熟和成熟大鼠的神经毒性作用。
我们通过鼻腔滴注，使新生大鼠从出生后第 3 天到第 15 天（每天一次）暴露于 PM2.5（2 或 10mg/kg 体重）。使用高架十字迷宫、强迫游泳和 Morris 水迷宫测试评估情绪和认知发育。收集海马组织并进行透射电镜观察和 Western blot 分析。
暴露于高剂量 PM2.5 的大鼠体重较低。行为测试结果表明，高剂量 PM2.5 暴露导致未成熟和成熟大鼠出现焦虑样症状增加，成熟大鼠出现明显的抑郁样行为，未成熟大鼠的空间学习和记忆能力受损，低剂量 PM2.5 暴露增加了未成熟大鼠的焦虑样行为。此外，高剂量 PM2.5 暴露导致未成熟和成熟大鼠的突触减少、突触后密度变薄、活性区缩短，并且未成熟大鼠的突触小泡蛋白（SYP）、生长相关蛋白-43（GAP43）和突触后密度-95（PSD95）表达减少，成熟大鼠的 SYP 和 PSD95 表达减少。此外，低剂量 PM2.5 暴露减少了未成熟大鼠 PSD95 的表达。此外，高剂量 PM2.5 暴露降低了未成熟和成熟大鼠脑中源性神经营养因子（BDNF）的表达和环磷腺苷反应元件结合蛋白（CREB）的磷酸化，而低剂量 PM2.5 暴露则减少了未成熟大鼠 BDNF 的表达和 CREB 的磷酸化。
我们的研究结果表明，PM2.5 通过破坏结构突触可塑性损害情绪和认知发育，可能通过 CREB/BDNF 信号通路。
