Chemically functionalized single-walled carbon nanotubes enhance the glutamate uptake characteristics of mouse cortical astrocytes
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Using a radioactive glutamate uptake assay and immunolabeling, we report that single-walled carbon nanotubes, chemically functionalized with polyethylene glycol (SWCNT-PEG), delivered as a colloidal solute, cause an increase in the uptake of extracellular glutamate by astrocytes and an increase in the immunoreactivity of the glutamate transporter GLAST on their cell surface, which is likely a consequence of an increase in the immunoreactivity of glial fibrillary acidic protein. Additional corollary is that astrocytes exposed to SWCNT-PEG became larger and stellate, morphological characteristics of maturation and heightened activity of these glial cells. These results imply that SWCNT-PEG could potentially be used as a viable candidate for neural prosthesis applications, perhaps to alleviate the death toll of neurons due to glutamate excitotoxicity, a pathological process observed in brain and spinal cord injuries.
KeywordsCarbon nanotubes Astrocytes Glial fibrillary acidic protein Glutamate excitotoxicity
Excitatory amino acid transporter
Glial fibrillary acidic protein
Glial l-glutamate transporter
Rho-associated protein kinase
Single-walled carbon nanotube
We thank Stephanie M. Robert and Dr. Harald Sontheimer, University of Alabama at Birmingham, for their help with the glutamate uptake study and Dr. Vladimir Grubišić for his constructive comments on a previous version of this manuscript. V. Parpura acknowledges the support of this work by National Institutes of Health (The Eunice Kennedy Shriver National Institute of Child Health and Human Development award HD078678).
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
- Gottipati MK, Bekyarova E, Brenner M, Haddon RC, Parpura V (2014) Changes in the morphology and proliferation of astrocytes induced by two modalities of chemically functionalized single-walled carbon nanotubes are differentially mediated by glial fibrillary acidic protein. Nano Lett 14:3720–3727. doi: 10.1021/nl4048114 PubMedCentralPubMedCrossRefGoogle Scholar
- Hughes EG, Maguire JL, McMinn MT, Scholz RE, Sutherland ML (2004) Loss of glial fibrillary acidic protein results in decreased glutamate transport and inhibition of PKA-induced EAAT2 cell surface trafficking. Brain Res Mol Brain Res 124:114–123. doi: 10.1016/j.molbrainres.2004.02.021 PubMedCrossRefGoogle Scholar
- Lau CL, O’Shea RD, Broberg BV, Bischof L, Beart PM (2011) The Rho kinase inhibitor Fasudil up-regulates astrocytic glutamate transport subsequent to actin remodelling in murine cultured astrocytes. Br J Pharmacol 163:533–545. doi: 10.1111/j.1476-5381.2011.01259.x PubMedCentralPubMedCrossRefGoogle Scholar
- Roman JA, Niedzielko TL, Haddon RC, Parpura V, Floyd CL (2011) Single-walled carbon nanotubes chemically functionalized with polyethylene glycol promote tissue repair in a rat model of spinal cord injury. J Neurotrauma 28:2349–2362. doi: 10.1089/neu.2010.1409 PubMedCentralPubMedCrossRefGoogle Scholar