PMID- 29550386 OWN - NLM STAT- MEDLINE DCOM- 20190321 LR - 20190321 IS - 1872-9711 (Electronic) IS - 0161-813X (Linking) VI - 66 DP - 2018 May TI - Maternal exposure to silver nanoparticles are associated with behavioral abnormalities in adulthood: Role of mitochondria and innate immunity in developmental toxicity. PG - 66-77 LID - S0161-813X(18)30085-8 [pii] LID - 10.1016/j.neuro.2018.03.006 [doi] AB - Silver nanoparticles (Ag-NPs) are currently used in a wide range of consumer products. Considering the small size of Ag-NPs, they are able to pass through variety of biological barriers and exert their effects. In this regard, the unique physicochemical properties of Ag-NPs along with its high application in the industry have raised concerns about their negative effects on human health. Therefore, it investigated whether prenatal exposure to low doses of Ag-NPs is able to induce any abnormality in the cognitive and behavioral performance of adult offspring. We gavaged pregnant NMRI mice with, 1) Deionized water as vehicle, 2) Ag-NPs 10 nm (0.26 mg/kg/day), 3) Ag-NPs 30 nm (0.26 mg/kg/day), and 4) AgNO(3) (0.26 mg/kg/day) from gestational day (GD) 0 until delivery day. At the postnatal day (PD) 1, our results showed that high concentration of silver is present in the brain of pups. Further, we observed mitochondrial dysfunction and upregulation of the genes relevant to innate immune system in the brain. At PD 60, results revealed that prenatal exposure to Ag-NPs provoked severe cognitive and behavioral abnormalities in male offspring. In addition, we found that prenatal exposure to Ag-NPs was associated with abnormal mitochondrial function and significant up-regulation of the genes relevant to innate immunity in the brain. Although the Ag-NPs have been considered as safe compounds at low doses, our results indicate that prenatal exposure to low doses of Ag-NPs is able to induce behavioral and cognitive abnormalities in adulthood. Also, we found that these effects are at least partly associated with hippocampal mitochondrial dysfunction and the activation of sterile inflammation during early stages of life. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Amiri, Shayan AU - Amiri S AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Yousefi-Ahmadipour, Aliakbar AU - Yousefi-Ahmadipour A AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Tissue Engineering and Applied Cell Sciences, Department of School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hosseini, Mir-Jamal AU - Hosseini MJ AD - Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. FAU - Haj-Mirzaian, Arya AU - Haj-Mirzaian A AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Momeny, Majid AU - Momeny M AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hosseini-Chegeni, Heshmat AU - Hosseini-Chegeni H AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Mokhtari, Tahmineh AU - Mokhtari T AD - Research Center of Nervous System Stem Cells, Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. FAU - Kharrazi, Sharmin AU - Kharrazi S AD - Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hassanzadeh, Gholamreza AU - Hassanzadeh G AD - Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Amini, Seyed Mohammad AU - Amini SM AD - Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Jafarinejad, Somayeh AU - Jafarinejad S AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Ghazi-Khansari, Mahmoud AU - Ghazi-Khansari M AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iran Nanosafety Network (INSN) of Iran Nanotechnology Initiative Council (INIC), Tehran, Iran. Electronic address: ghazikha@sina.tums.ac.ir. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180314 PL - Netherlands TA - Neurotoxicology JT - Neurotoxicology JID - 7905589 RN - 3M4G523W1G (Silver) SB - IM MH - Animals MH - Brain/*drug effects MH - Depression/chemically induced MH - Encephalitis/chemically induced/immunology MH - Female MH - Hippocampus/drug effects/metabolism MH - Immunity, Innate/*drug effects MH - Male MH - *Maternal Exposure MH - Metal Nanoparticles/chemistry/*toxicity MH - Mice MH - Mitochondria/*drug effects/metabolism MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced/immunology/metabolism MH - Silver/chemistry/*toxicity OTO - NOTNLM OT - Behavioral dysfunction OT - Hippocampus OT - Innate immunity OT - Mitochondria OT - Prenatal stage OT - Silver nanoparticles EDAT- 2018/03/20 06:00 MHDA- 2019/03/22 06:00 CRDT- 2018/03/19 06:00 PHST- 2017/06/20 00:00 [received] PHST- 2018/03/06 00:00 [revised] PHST- 2018/03/10 00:00 [accepted] PHST- 2018/03/20 06:00 [pubmed] PHST- 2019/03/22 06:00 [medline] PHST- 2018/03/19 06:00 [entrez] AID - S0161-813X(18)30085-8 [pii] AID - 10.1016/j.neuro.2018.03.006 [doi] PST - ppublish SO - Neurotoxicology. 2018 May;66:66-77. doi: 10.1016/j.neuro.2018.03.006. Epub 2018 Mar 14.