Switching on microglia with electro-conductive multi walled carbon nanotubes

Abstract

OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. This is an author-deposited version published in : http://oatao. a b s t r a c tWe explored the mechanisms underlying microglia cell-carbon nanotube interactions in order to investigate whether electrical properties of Carbon-Nanotubes (CNTs) could affect microglia brain cells function and phenotype. We analyzed the effects induced by highly electro-conductive Multi-WalledCarbon-Nanotubes (a-MWCNTs), on microglia cells from rat brain cortex and compared the results with those obtained with as prepared not conductive MWCNTs (MWCNTs) and redox-active Double-WalledCarbon-Nanotubes (DWCNTs). Cell viability and CNT capacity to stimulate the release of nitric oxide (NO), pro-inflammatory (IL-1b, TNF-a) and anti-inflammatory (IL-10, TGF-b1) cytokines and neurotrophic factors (mNGF) were assessed.Electro-conductive MWCNTs, besides not being cytotoxic, were shown to stimulate, at 24 h cell exposure, classical "M1 00 microglia activation phenotype, increasing significantly the release of the main pro-inflammatory cytokines. Conversely, after 48 h cell exposure, they induced the transition from classical "M1 00 to alternative "M2 00 microglia phenotype, supported by anti-inflammatory cytokines and neuroprotective factor mNGF release. The analysis of cell morphology change, by tubulin and CD-206 þ labelling showed that M2 phenotype was much more expressed at 48 h in cells exposed to aMWCNTs than in untreated cells.Our data suggest that the intrinsic electrical properties of CNTs could be exploited to modulate microglia phenotype and function stimulating microglia anti-inflammatory potential.

Distribution in the brain and possible neuroprotective effects of intranasally delivered multi-walled carbon nanotubes

“…The exploration of delivering CNTs to the CNS in an efficient and not invasive way was specifically driven by our previous observation concerning the ability of electroconductive MWCNTs to change phenotype and function of microglial cells, positively regulating the expression of neuroprotective molecular markers such as mature NGF 12 . Herein, we revealed that both MWCNTs delivered through the olfactory epithelium consistently diffused into the brain parenchyma, reaching at least medial regions of the brain, following the rostro-caudal axis, such as the hippocampus, thalamus and hypothalamus.…”

“…We already demonstrated the ability of annealed MWCNTs to positively regulate the expression of molecular markers of neurodegenerative diseases, inducing the release of the neuroprotective factor mNGF in vitro 12 . Following these findings, we aimed to verify the hypothesis that a-MWCNTs 2 were able to stimulate also in vivo a pro-neurotrophic function in the brain areas reached after their delivery via the olfactory route.…”

“…In the last years CNTs were investigated for their beneficial use in nervous system tissue engineering and recent researches increasingly focused on their exploitation as nanotools to modulate neurobiological processes, such as growth and organization of neural networks, in order to accomplish nerve tissue reconstruction and repair 4,5 . CNTs were shown to be promising nanomaterials for new tissue-engineered products such as prosthetic neuronal devices [6][7][8] as well as drug delivery devices 9 , to affect neurons, astrocytes and microglia cell functions [10][11][12] and to sustain and promote electrical activity in networks of cultured neurons 13 . Moreover, functionalized carbon nanotubes (f-CNTs) were reported to induce neurite outgrowth 14,15 and CNT substrates are known to boost neuronal electrical signalling increasing GABAergic and glutamatergic synaptogenesis 16,17 and to directly stimulate brain circuit activity 13 .…”

Neurotoxicity of metal‐containing nanoparticles and implications in glial cells

“…The latter also produce anti‐inflammatory cytokines such as IL‐4, IL‐10 and TGF‐β to help resolve the inflammatory response (Desestret et al, 2013). Fiorito et al found that a classical “M1” microglial cell‐activation phenotype increased the release of nitric oxide and proinflammatory cytokines (IL‐1β, TNF‐α) induced by NPs (Fiorito et al, 2018). In addition, NPs found in air pollutants increase neuroinflammation and alter brain functions.…”

“…The latter also produce anti-inflammatory cytokines such as IL-4, IL-10 and TGF-β to help resolve the inflammatory response (Desestret et al, 2013). Fiorito et al found that a classical "M1" microglial cell-activation phenotype increased the release of nitric oxide and proinflammatory cytokines (IL-1β, TNFα) induced by NPs(Fiorito et al, 2018). In addition, NPs found in air pollutants increase neuroinflammation and alter brain functions.Duffy et al reported that activation of BV2 microglial cells and TNF-α secretion was induced by AgNPs, so microglial cells could be surrogate biomarkers of neuroinflammation(Duffy et al, 2016).Microglial cells and ALTs are critical for brain functions.…”