title: Effect of O-methyl-β-cyclodextrin-modified magnetic nanoparticles on the uptake and extracellular level of l-glutamate in brain nerve terminals.
abstract: Changes in cholesterol concentration in the plasma membrane of presynaptic nerve terminals nonspecifically modulate glutamate transport and homeostasis in the central nervous system. Reduction of the cholesterol content in isolated rat brain nerve terminals (synaptosomes) using cholesterol-depleting agents decreases the glutamate uptake and increases the extracellular level of glutamate in nerve terminals. Extraction of cholesterol from the plasma membrane and its further removal from the synaptosomes by external magnetic field can be achieved by means of magnetic nanoparticles with immobilized cholesterol-depleting agent such as O-methyl-β-cyclodextrin (MCD). A simple approach is developed for preparation of maghemite (γ-Fe2O3) nanoparticles containing chemically bonded MCD. The method is based on preparation of a silanization agent containing MCD. It is synthesized by the reaction of triethoxy(3-isocyanatopropyl)silane with MCD. Base-catalyzed silanization of superparamagnetic γ-Fe2O3provides a relatively stable colloid product containing 48μmol of MCDg-1. MCD-modified γ-Fe2O3nanoparticles decrease the initial rate of the uptake and accumulation of l-[14C]glutamate and increase the extracellular l-[14C]glutamate level in the preparation of nerve terminals. The effect of MCD-immobilized nanoparticles is the same as that of MCD solution; moreover, magnetic manipulation of the nanoparticles enables removal of bonded cholesterol.
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic. Electronic address: horak@imc.cas.cz.
authors.forename: Daniel
authors.initials: D
authors.lastname: Horák
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Beneš
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Procházková
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Trchová
authors.affiliation: Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine; 9 Leontovich Str., Kiev, 01601, Ukraine.
authors.forename: Arsenii
authors.initials: A
authors.lastname: Borysov
authors.affiliation: Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine; 9 Leontovich Str., Kiev, 01601, Ukraine.
authors.forename: Artem
authors.initials: A
authors.lastname: Pastukhov
authors.affiliation: Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine; 9 Leontovich Str., Kiev, 01601, Ukraine.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Paliienko
authors.affiliation: Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine; 9 Leontovich Str., Kiev, 01601, Ukraine.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Borisova
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D005290:Ferric Compounds / Q000737:chemistry; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012821:Silanes / Q000737:chemistry; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D012821:Silanes; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C000499:ferric oxide; D018698:Glutamic Acid; D002784:Cholesterol
keywords: Cholesterol; Glutamate; Maghemite nanoparticles; Nerve terminals; O-Methyl-β-cyclodextrin