TY - JOUR
T1 - Potentiation of NMDA receptor-mediated synaptic responses by microglia
AU - Moriguchi, Shigeki
AU - Mizoguchi, Yoshito
AU - Tomimatsu, Yoshiro
AU - Hayashi, Yoshinori
AU - Kadowaki, Tomoko
AU - Kagamiishi, Yoshifumi
AU - Katsube, Nobuo
AU - Yamamoto, Kenji
AU - Inoue, Kazuhide
AU - Watanabe, Shigenori
AU - Nabekura, Junichi
AU - Nakanishi, Hiroshi
N1 - Funding Information:
We thank Dr. William Marszalec for the critical reading of the manuscript. This work was supported by a Grant-in-Aid for the Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (HN), and a Grant-in-Aid for the Creation of Innovations through Business–Academic–Public Sector Cooperation of Japan (HN).
PY - 2003/11/26
Y1 - 2003/11/26
N2 - To study the influence of microglia on glutamatergic synaptic transmission in the acute phase of neuronal injury, we first examined the effects of primary cultured microglia transferred onto the organotypic cortical slice cultures. In these microglia-transferred cortical slice cultures, stimulation of the subcortical white matter induced fast excitatory postsynaptic potentials followed by N-methyl-D-aspartate (NMDA) receptor-mediated plateau-like potentials that were never observed in control slice cultures. A similar potentiation of NMDA receptor-mediated postsynaptic responses was also observed by an application of a microglial-conditioned medium (MCM, 10% v/v) in acute cortical slices. These effects of MCM disappeared after boiling or incubation with proteinase K. After fractionation of MCM by anion-exchange chromatography, the enhancing activity of each fraction was quantitated electrophysiologically. When each fraction was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the fraction 24 which showed the most potent enhancing activity on NMDA receptor-mediated responses contained a relatively strong protein band with a molecular mass of approximately 70 kDa. MCM also enhanced both glutamate- and NMDA-induced inward currents recorded from acutely isolated cortical neurons. It was also noted that glutamate and NMDA induced transient large inward currents during an application of MCM, which were never observed in the control condition. These observations strongly suggest that NMDA receptor-mediated responses can be potentiated by both heat- and protease-labile (presumably 70-kDa proteins) molecules released from microglia.
AB - To study the influence of microglia on glutamatergic synaptic transmission in the acute phase of neuronal injury, we first examined the effects of primary cultured microglia transferred onto the organotypic cortical slice cultures. In these microglia-transferred cortical slice cultures, stimulation of the subcortical white matter induced fast excitatory postsynaptic potentials followed by N-methyl-D-aspartate (NMDA) receptor-mediated plateau-like potentials that were never observed in control slice cultures. A similar potentiation of NMDA receptor-mediated postsynaptic responses was also observed by an application of a microglial-conditioned medium (MCM, 10% v/v) in acute cortical slices. These effects of MCM disappeared after boiling or incubation with proteinase K. After fractionation of MCM by anion-exchange chromatography, the enhancing activity of each fraction was quantitated electrophysiologically. When each fraction was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the fraction 24 which showed the most potent enhancing activity on NMDA receptor-mediated responses contained a relatively strong protein band with a molecular mass of approximately 70 kDa. MCM also enhanced both glutamate- and NMDA-induced inward currents recorded from acutely isolated cortical neurons. It was also noted that glutamate and NMDA induced transient large inward currents during an application of MCM, which were never observed in the control condition. These observations strongly suggest that NMDA receptor-mediated responses can be potentiated by both heat- and protease-labile (presumably 70-kDa proteins) molecules released from microglia.
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U2 - 10.1016/j.molbrainres.2003.09.007
DO - 10.1016/j.molbrainres.2003.09.007
M3 - Article
C2 - 14625083
AN - SCOPUS:10744227991
SN - 0169-328X
VL - 119
SP - 160
EP - 169
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 2
ER -