Subacute silica nanoparticle exposure induced oxidative stress and inflammation in rat hippocampus combined with disruption of cholinergic system and behavioral functions

被引:13
作者
Boukholda, Khadija [1 ]
Gargouri, Brahim [1 ,2 ]
Aouey, Bakhta [1 ]
Attaai, Abdelraheim [3 ]
Abd Elkodous, Mohamed [4 ]
Najimi, Mohamed [5 ]
Fiebich, L. Bernd [2 ]
Bouchard, Michele [6 ]
Fetoui, Hamadi [1 ]
机构
[1] Univ Sfax, Fac Sci Sfax, Lab Toxicol Microbiol & Environm Hlth 17ES06, BP1171, Sfax 3000, Tunisia
[2] Univ Freiburg, Med Ctr, Neurochem & Neuroimmunol Res Grp, Fac Med,Dept Psychiat & Psychotherapy, Hauptstr 5, D-79104 Freiburg, Germany
[3] Assiut Univ, Fac Vet Med, Dept Anat & Histol, Assiut, Egypt
[4] Toyohashi Univ Technol, Dept Elect & Elect Informat Engn, 1-Hibarigaoka,Tempaku Cho, Toyohashi, Aichi 4418580, Japan
[5] Sultan Moulay Slimane Univ, Fac Sci & Tech, Bioengn Lab, Beni Mellal 23000, Morocco
[6] Univ Montreal, Publ Hlth Res Ctr CReSP, Chair Toxicol Risk Assessment & Management, Dept Environm & Occupat Hlth, Roger Gaudry Bldg,U424,POB 6128,Main Stn, Montreal, PQ H3C 3J7, Canada
关键词
Silica nanoparticles; Signaling pathway; Oxidative stress; Neuroinflammation; hippocampus; IN-VIVO; TOXICITY; NEUROTOXICITY; MECHANISMS; DIOXIDE; SILVER; CELLS; CYTOTOXICITY; MODULATION; MEMORY;
D O I
10.1016/j.impact.2021.100358
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Increasing environmental exposure to silica nanoparticles (SiNPs) and limited neurotoxicity studies pose a challenge for safety evaluation and management of these materials. This study aimed to explore the adverse effects and underlying mechanisms of subacute exposure to SiNPs by the intraperitoneal route on hippocampus function in rats. Data showed that SiNPs induced a significant increase in oxidative/nitrosative stress markers including reactive oxygen species (ROS), malondialdehyde (MDA), protein oxidation (PCO) and nitrite (NO) production accompanied by reduced antioxidant enzyme activity (catalase, superoxide dismutase, and glutathione peroxidase) and decreased glutathione (GSH). Phenotypically, SiNPs exhibited spatial learning and memory impairment in the Morris water maze (MWM) test, a decrease of the discrimination index in the novel object recognition test (NORT) and higher anxiety-like behavior. SiNPs affected the cholinergic system as reflected by reduced acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. In addition, SiNPs significantly increased mRNA expression level of genes related to inflammation (TNF-alpha, IL-1 beta, IL-6, and COX-2) and decreased mRNA expression level of genes related to cholinergic system including choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), AChE, muscarinic acetylcholine receptor M1 (m1AChR) and nicotinic acetylcholine receptors (nAChR). Histopathological results further showed an alteration in the hippocampus of treated animals associated with marked vacuolation in different hippocampus areas. These findings provide new insights into the molecular mechanism of SiNPs-induced hippocampal alterations leading to impairment of cognitive and behavioral functions, and implicating oxidative stress and inflammation in the hippocampus, as well as disruption of cholinergic system.
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页数:15
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