title: Synaptic degeneration in rat brain after prolonged oral exposure to silver nanoparticles.
abstract: Neurotoxicity of silver nanoparticles has been confirmed in both in vitro and in vivo studies. However, the mechanisms of the toxic action have not been fully clarified. Since nanoparticles are likely to have the ability to enter the brain and significantly accumulate in this organ, it is important to investigate their neurotoxic mechanisms. Here we examine the effect of prolonged exposure of rats to small (10nm) citrate-stabilized silver nanoparticles (as opposed to the ionic silver) on synapse ultrastructure and specific proteins. Administration of both nanosilver and ionic silver over a two-week period resulted in ultrastructural changes including blurred synapse structure and strongly enhanced density of synaptic vesicles clustering in the center of the presynaptic part. Disturbed synaptic membrane leading to liberation of synaptic vesicles into neuropil, which testifies for strong synaptic degeneration, was characteristic feature observed under AgNPs exposure. Also a noteworthy finding was the presence of myelin-like structures derived from fragmented membranes and organelles which are associated with neurodegenerative processes. Additionally, we observed significantly decreased levels of the presynaptic proteins synapsin I and synaptophysin, as well as PSD-95 protein which is an indicator of postsynaptic densities. The present study demonstrates that exposure of adult rats to both forms of silver leads to ultrastructural changes in synapses. However, it seems that small AgNPs lead to more severe synaptic degeneration, mainly in the hippocampal region of brain. The observations may indicate impairment of nerve function and, in the case of hippocampus, may predict impairment of cognitive processes.
authors.affiliation: Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Skalska
authors.affiliation: Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frontczak-Baniewicz
authors.affiliation: Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland. Electronic address: lidkas@imdik.pan.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Strużyńska
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D055032:Electron Microscope Tomography; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism; D053758:Nanoparticles / Q000378:metabolism / Q000633:toxicity* / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018030:Silver Compounds / Q000097:blood / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D016704:Synapsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018030:Silver Compounds; D016704:Synapsins; D016708:Synaptophysin
keywords: Myelin-like bodies; Nanotoxicity; PSD-95; Synapsin I; Synaptophysin