Academic journal article Environmental Health Perspectives

Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia

Academic journal article Environmental Health Perspectives

Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia

Article excerpt

BACKGROUND: Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for non-viral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes.

OBJECTIVE: We examined the effects of SiNP exposure using primary rat microglia.

METHODS: We observed microglial uptake of SiNPs using transmission electron and fluorescence confocal microscopy. Microglial functions, including phagocytosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), expression of proinflammatory genes, and cytokine release, were measured after SiNP exposure at different concentrations.

RESULTS: Microglia are capable of avidly taking up SiNPs at all concentrations tested. These same concentrations did not elicit cytotoxicity or a change in phagocytic activity. SiNPs did increase the productions of both intracellular ROS and RNS. We also observed a significant decrease in tumor necrosis factor-[alpha] gene expression at all concentrations tested and a significant increase in COX-2 (cyclooxygenase-2) gene expression at the highest concentration of SiNPs. Analysis of cytokine release showed a detectable level of interleukin-1[beta].

CONCLUSIONS: This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons.

KEY WORDS: inflammation, microglia, nanoparticle, neurotoxicity, ROS, RNS, silica. Environ Health Perspect 118:589-595 (2010). doi:10.1289/ehp.0901534 [Online 21 December 2009]

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The use of engineered nanoparticles (NPs) has increased significantly in the past decade. Because of the flexibility of producing NPs of different sizes, shapes, and surface modifications, engineered NPs can be used in a variety of applications, including skin care products, foods, electronics, and medicine. Anthropogenic sources of NPs also emerge from power plants and industries. It is likely that humans will be exposed to NPs through dermal absorption, ingestion, and inhalation. This may pose a health concern because studies have shown that NPs can elicit adverse cellular effects in vitro (Fubini and Hubbard 2003; Napierska et al. 2009; Park and Park 2009). A recent study has shown that workers occupationally exposed to NPs for 5-13 months exhibited symptoms of pulmonary fibrosis, with NPs present in the cytoplasm of pulmonary epithelial and mesothelial cells (Song et al. 2009).

Entry of engineered NPs into the brain may be possible via several pathways. One of the well-studied pathways is the nose-to-brain transport through the olfactory epithelium. Olfactory sensory neurons (OSNs) reside in the olfactory epithelium and have processes in direct contact with the outside environment. Thus, NPs might be able to gain access to the brain by OSNs and its projections to the olfactory bulb and subsequently to other regions in the brain (Calderon-Garciduenas et al. 2002; Oberdorster et al. 2004). Another possible nose-to-brain transport can occur through the trigeminal nerve, the largest of the cranial nerves. Afferent neurons from the trigeminal nerve pass directly through the nasal mucosa and enter the brainstem at the level of the pons (Mistry et al. 2009). For example, in rats, intranasal administration of the neurotrophic factor insulin-like growth factor-1 (IGF-1) resulted in the delivery of IGF-1 to both the olfactory bulb and brainstem areas (Thorne et al. 2004). In addition, NPs can be synthetically engineered to bypass the blood-brain barrier. …

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