title: Silver nanoparticle exposure induces rat motor dysfunction through decrease in expression of calcium channel protein in cerebellum.
abstract: Silver nanoparticles (AgNPs) are currently used widely, however, their impact on central nervous system still remains ambiguous and needs to be elucidated. This study is performed to investigate the neurotoxicity of AgNPs and illustrate the potential molecular mechanism. Neonatal Sprague-Dawley (SD) rats are exposed to AgNPs by intranasal instillation for 14 weeks. It is demonstrated that AgNPs exposure causes cerebellar ataxia like symptom in rats, evidenced by dysfunction of motor coordination and impairment of locomotor activity. Observation of cerebellum section reveals that AgNPs can provoke destruction of cerebellum granular layer with concomitant activation of glial cells. AgNPs treatment decreases calcium channel protein (CACNA1A) levels in cerebellum without changing potassium channel protein (KCNA1) levels. The levels of silver in rat cerebellum tissue are correlated with exposure doses. In vitro experiments reveal that AgNPs treatment significantly reduces the protein and mRNA levels of CACNA1A in primary cultured cerebellum granule cells (CGCs). These findings suggest that AgNPs-induced rat motor dysfunction is associated with CACNA1A expression decrease, which reveals the underlying molecular mechanism for the neurotoxicity of AgNPs. Possible counteractions may accordingly be suggested to attenuate the unexpected harmful effects in biological applications of AgNPs.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
authors.forename: Nuoya
authors.initials: N
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China. Electronic address: zhouqf@rcees.ac.cn.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
authors.forename: Guibin
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000032:analysis*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000633:toxicity*; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D012834:Silver; C491367:Cacna1a protein, rat; D020864:Calcium Channels, N-Type
keywords: Calcium channel protein; Locomotor activity impairment; Motor coordination dysfunction; Neurotoxicity; Silver nanoparticles