Changes in mint1, a novel synaptic protein, after transient global ischemia in mouse hippocampus

Mints (munc18-interacting proteins) are novel multimodular adapter proteins in membrane transport and organization. Mint1, a neuronal isoform, is invo lved in synaptic vesicle exocytosis. Its potential effects on development o f ischemic damage to neurons have not yet been evaluated. The authors exami ned changes in mint1 and other synaptic proteins by immunohistochemistry af ter transient global ischemia in mouse hippocampus. In sham-ischemic mice, immunoreactivity for mint1 was rich in fibers projecting from the entorhina l cortex to the hippocampus and in the mossy fibers linking the granule cel ls of the dentate gyrus to CA3 pyramidal neurons. Munc18-1, a binding partn er of mint1, was distributed uniformly throughout the hippocampus, and syna ptophysin 2, a synaptic vesicle protein, was localized mainly in mossy fibe rs. After transient global ischemia, mint1 immunoreactivity in mossy fibers was dramatically decreased at 1 day of reperfusion but actually showed enh ancement at 3 days. However, munc18-1 and synaptophysin 2 were substantiall y expressed in the same region throughout the reperfusion period. These fin dings suggest that mint1 participates in neuronal transmission along the ex citatory pathway linking the entorhinal cortex to CA3 in the hippocampus. B ecause mint1 was transiently decreased in the mossy fiber projection after ischemia, functional impairment of neuronal transmission in the projection from the dentate gyrus to CA3 pyramidal neurons might be involved in delaye d neuronal death.