Counteraction by repetitive daily exposure to static magnetism against sustained blockade of N-methyl-D-aspartate receptor channels in cultured rat hippocampal neurons.
In rat hippocampal neurons cultured with the antagonist for N-methyl-D-aspartate (NMDA) receptors dizocilpine (MK-801) for 8 days in vitro (DIV), a significant decrease was seen in the expression of microtubule-associated protein-2 (MAP-2) as well as mRNA for both brain-derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43), in addition to decreased viability. MK-801 not only decreased the expression of the NR1 subunit of NMDA receptors but also increased NR2A expression, without affecting NR2B expression. Repetitive daily exposure to static magnetic fields at 100 mT for 15 min led to a decrease in the expression of MAP-2, without significantly affecting cell viability or the expression of neuronal nuclei (NeuN) and GAP-43. However, the repetitive magnetism prevented decreases in both BDNF mRNA and MAP-2 and additionally increased the expression of NR2A subunit, without altering NR1 expression in neurons cultured in the presence of MK-801. Repetitive magnetism was also effective in preventing the decrease by MK-801 in the ability of NMDA to increase intracellular free Ca2+ ions, without affecting the decrease in the maximal response. These results suggest that repetitive magnetism may at least in part counteract the neurotoxicity of MK-801 through modulation of the expression of particular NMDA receptor subunits in cultured rat hippocampal neurons.
Hirai
Takao
T
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, Ishikawa, Japan.
Taniura
Hideo
H
Goto
Yasuaki
Y
Tamaki
Keisuke
K
Oikawa
Hirotaka
H
Kambe
Yuki
Y
Ogura
Masato
M
Ohno
Yu
Y
Takarada
Takeshi
T
Yoneda
Yukio
Y
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D008280:Magnetics; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D002118:Calcium; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D008869:Microtubule-Associated Proteins; D016202:N-Methylaspartate; D010751:Phosphopyruvate Hydratase; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate