title: Manipulation of isolated brain nerve terminals by an external magnetic field using D-mannose-coated γ-Fe2O3 nano-sized particles and assessment of their effects on glutamate transport.
abstract: The manipulation of brain nerve terminals by an external magnetic field promises breakthroughs in nano-neurotechnology. D-Mannose-coated superparamagnetic nanoparticles were synthesized by coprecipitation of Fe(II) and Fe(III) salts followed by oxidation with sodium hypochlorite and addition of D-mannose. Effects of D-mannose-coated superparamagnetic maghemite (γ-Fe2O3) nanoparticles on key characteristics of the glutamatergic neurotransmission were analysed. Using radiolabeled L-[(14)C]glutamate, it was shown that D-mannose-coated γ-Fe2O3 nanoparticles did not affect high-affinity Na(+)-dependent uptake, tonic release and the extracellular level of L-[(14)C]glutamate in isolated rat brain nerve terminals (synaptosomes). Also, the membrane potential of synaptosomes and acidification of synaptic vesicles was not changed as a result of the application of D-mannose-coated γ-Fe2O3 nanoparticles. This was demonstrated with the potential-sensitive fluorescent dye rhodamine 6G and the pH-sensitive dye acridine orange. The study also focused on the analysis of the potential use of these nanoparticles for manipulation of nerve terminals by an external magnetic field. It was shown that more than 84.3 ± 5.0% of L-[(14)C]glutamate-loaded synaptosomes (1 mg of protein/mL) incubated for 5 min with D-mannose-coated γ-Fe2O3 nanoparticles (250 µg/mL) moved to an area, in which the magnet (250 mT, gradient 5.5 Т/m) was applied compared to 33.5 ± 3.0% of the control and 48.6 ± 3.0% of samples that were treated with uncoated nanoparticles. Therefore, isolated brain nerve terminals can be easily manipulated by an external magnetic field using D-mannose-coated γ-Fe2O3 nanoparticles, while the key characteristics of glutamatergic neurotransmission are not affected. In other words, functionally active synaptosomes labeled with D-mannose-coated γ-Fe2O3 nanoparticles were obtained.
authors.affiliation: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev, 01601, Ukraine.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Borisova
authors.affiliation: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev, 01601, Ukraine.
authors.forename: Natalia
authors.initials: N
authors.lastname: Krisanova
authors.affiliation: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev, 01601, Ukraine ; The Biological Faculty, Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str, Kiev, Ukraine.
authors.forename: Arsenii
authors.initials: A
authors.lastname: Borуsov
authors.affiliation: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev, 01601, Ukraine.
authors.forename: Roman
authors.initials: R
authors.lastname: Sivko
authors.affiliation: The Biological Faculty, Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str, Kiev, Ukraine.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Ostapchenko
authors.affiliation: The Department of Polymer Particles, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Babic
authors.affiliation: The Department of Polymer Particles, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Horak
keywords: D-mannose; extracellular level; glutamate uptake and release; manipulation by an external magnetic field; membrane potential; nanoparticles; rat brain nerve terminals; synaptic vesicle acidification; γ-Fe2O3