title: Silver nanoparticles (AgNPs) cause degeneration of cytoskeleton and disrupt synaptic machinery of cultured cortical neurons.
abstract: BACKGROUND
  Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.
  
  
  RESULTS
  Here we examine the effects of ultra fine scales (20 nm) of AgNPs at various concentrations (1, 5, 10 and 50 μg/ml) on primary rat cortical cell cultures. We found that AgNPs (at 1-50 μg/ml) not only inhibited neurite outgrowth and reduced cell viability of premature neurons and glial cells, but also induced degeneration of neuronal processes of mature neurons. Our immunocytochemistry and confocal microscopy studies further demonstrated that AgNPs induced the loss of cytoskeleton components such as the β-tubulin and filamentous actin (F-actin). AgNPs also dramatically reduced the number of synaptic clusters of the presynaptic vesicle protein synaptophysin, and the postsynaptic receptor density protein PSD-95. Finally, AgNP exposure also resulted in mitochondria dysfunction in rat cortical cells.
  
  
  CONCLUSIONS
  Taken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.forename: Cortt
authors.initials: C
authors.lastname: Piett
authors.forename: Svetlana
authors.initials: S
authors.lastname: Farkas
authors.forename: Munir
authors.initials: M
authors.lastname: Qazzaz
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology*; D005453:Fluorescence; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects / Q000473:pathology*; D013572:Synaptic Vesicles / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D005904:Glial Fibrillary Acidic Protein; D014404:Tubulin; D012834:Silver