The entry of manganese ions into the brain is accelerated by the activation of N-methyl-D-aspartate receptors.
Manganese-enhanced magnetic resonance imaging (MEMRI) is receiving increased interest as a valuable tool for monitoring the physiological functions in the animal brain based on the ability of manganese ions to mimic calcium ions entering to excitable cells. Here the possibility that in vivo MEMRI can detect the entry of manganese ions (Mn2+) in the brain of rats behaving without intended stimulation is tested. This hypothesis was a result of the unexpected observation that Mn2+-dependent signal enhancement was dramatically suppressed in ketamine-anesthetized rats compared with other anesthetics, such as urethane, pentobarbital and isoflurane. The effects of noncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonists, ketamine and MK-801, on MEMRI for MnCl2 injected rats were examined. Treatment with MK-801 suppressed the signal enhancement more effectively than with ketamine. NMDAR agonists, glutamate (100 mg/kg) and N-methyl-d-aspartate (NMDA) (35 mg/kg), enhanced the signal intensities on MEMRI, and this signal enhancement was completely antagonized by MK-801. The systemic administration of the competitive NMDAR antagonist, D-2-amino-5-phosphono-pentanoate (D-AP5), which does not cross the blood-brain barrier (BBB), showed no effects on the signal enhancement induced by NMDA and glutamate. A selective AMPA receptor (AMPAR) antagonist, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), did not block the signal enhancement. These data indicated that the Mn2+-dependent signal enhancement took place as a result of the activation of glutamatergic neurons through NMDAR, but not through AMPAR in the brain.
Itoh
K
K
Laboratory for Brain Science, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki-shi, Kagawa, Japan. itoh@kph.bunri-u.ac.jp
Sakata
M
M
Watanabe
M
M
Aikawa
Y
Y
Fujii
H
H
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese / Q000378:metabolism*; D017895:Manganese Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017895:Manganese Compounds; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D008345:Manganese