Changes in the distribution of 1P1-antigen in the developing chick retina have been examined by indirect immunofluorescence staining technique using the novel monoclonal antibody (MAb) 1P1. Expression of the 1P1 antig...Changes in the distribution of 1P1-antigen in the developing chick retina have been examined by indirect immunofluorescence staining technique using the novel monoclonal antibody (MAb) 1P1. Expression of the 1P1 antigen was found to be regulated in radial as well as in tangential dimension of the retina, being preferentially or exclusively located in the inner and outer plexiform layers of the neural retina depending on the stages of development. With the onset of the formation of the inner plexiform layer 1P1 antigen becomes expressed in the retina. With progressing differentiation of the inner plexiform layer 1P1 immunofluorescence revealed 2 subbands at E9 and 6 sub-bands at E18. At postnatal stages (after P3) immunoreac-tivity was reduced in an inside-outside sequence leading to the complete absence of the 1P1 antigen in adulthood. 1P1 antigen expression in the outer plexiform layer was also subject to developmental regulation. The spatio-temporal pattern of 1P1 antigen expression was correlated with the time course of histological differentiation of chick retina, namely the synapse rich plexiform layers. Whether the 1P1 antigen was functionally involved in dendrite extension and synapse formation was discussed.展开更多
Cortical spreading depression (CSD) is a transient synaptic excitation, followed by depression, which can propagate slowly across cortex, subcortex and retina. CSD is implicated in migraine with aura and may lead to m...Cortical spreading depression (CSD) is a transient synaptic excitation, followed by depression, which can propagate slowly across cortex, subcortex and retina. CSD is implicated in migraine with aura and may lead to migraine pain. CSD can be suppressed by inhibition of both NR2A and NR2B containing N-methyl-D-aspartic acid (NMDA) receptors. However, whether there is a synergistic effect of co-inhibition of NR2A and NR2B containing receptors on CSD remains unknown. In this study, an efficient in vitro model of migraine with intrinsic optical imaging approach was applied to address this role of co-activation of both NR2A and NR2B in CSD. The results showed that co-application of NVP-AAM077, a drug selectively targeting for NR2A and Ro 25-6981, a drug selectively targeting for NR2B containing receptors, showed synergistic inhibitory effects on propagation rate and the magnitude of CSD in a concentration dependent manner in chick retina. Inhibition of CSD propagation was also observed by a clinical acceptable drug that antagonizes both NR2A and NR2B containing receptors, memantine, at 10 μM. These data suggest that combinational use of antagonists selectively targeting NR2A and NR2B containing receptors could be a useful strategy for preventative treatment of migraine with improved efficacy with potential alleviated side effects.展开更多
基金This work was completed in Max-Planck vip Laboratory at the shanghai Institrte of Cell Biology,Academia Sinica,as a collabgorative project of 3 Institutes.
文摘Changes in the distribution of 1P1-antigen in the developing chick retina have been examined by indirect immunofluorescence staining technique using the novel monoclonal antibody (MAb) 1P1. Expression of the 1P1 antigen was found to be regulated in radial as well as in tangential dimension of the retina, being preferentially or exclusively located in the inner and outer plexiform layers of the neural retina depending on the stages of development. With the onset of the formation of the inner plexiform layer 1P1 antigen becomes expressed in the retina. With progressing differentiation of the inner plexiform layer 1P1 immunofluorescence revealed 2 subbands at E9 and 6 sub-bands at E18. At postnatal stages (after P3) immunoreac-tivity was reduced in an inside-outside sequence leading to the complete absence of the 1P1 antigen in adulthood. 1P1 antigen expression in the outer plexiform layer was also subject to developmental regulation. The spatio-temporal pattern of 1P1 antigen expression was correlated with the time course of histological differentiation of chick retina, namely the synapse rich plexiform layers. Whether the 1P1 antigen was functionally involved in dendrite extension and synapse formation was discussed.
文摘Cortical spreading depression (CSD) is a transient synaptic excitation, followed by depression, which can propagate slowly across cortex, subcortex and retina. CSD is implicated in migraine with aura and may lead to migraine pain. CSD can be suppressed by inhibition of both NR2A and NR2B containing N-methyl-D-aspartic acid (NMDA) receptors. However, whether there is a synergistic effect of co-inhibition of NR2A and NR2B containing receptors on CSD remains unknown. In this study, an efficient in vitro model of migraine with intrinsic optical imaging approach was applied to address this role of co-activation of both NR2A and NR2B in CSD. The results showed that co-application of NVP-AAM077, a drug selectively targeting for NR2A and Ro 25-6981, a drug selectively targeting for NR2B containing receptors, showed synergistic inhibitory effects on propagation rate and the magnitude of CSD in a concentration dependent manner in chick retina. Inhibition of CSD propagation was also observed by a clinical acceptable drug that antagonizes both NR2A and NR2B containing receptors, memantine, at 10 μM. These data suggest that combinational use of antagonists selectively targeting NR2A and NR2B containing receptors could be a useful strategy for preventative treatment of migraine with improved efficacy with potential alleviated side effects.
