| 日本神経化学会第2回優秀受賞者講演 |
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| 1L4
Promotion of glial cell research by virtue of transgenic approach
Tanaka Kenji
Department of Neuropsychiatry, School of Medicine, Keio Univ
Glial cells are present in every brain region and show complex interactions with neurons. Therefore, when observing or manipulating glial cell functions, glial cell-specific expression of functional molecules is vital. These functional molecules should be fully expressed in transfected glial cells in a cell type-specific manner to exert their activities. In general, however, it is not easy to simultaneously achieve both a high level and a cell type-specific expression. To accomplish cell type-specific expression of functional probes in the brain, many researchers have employed local viral injections as a means to introduce those genes. However, viral injection via a needle causes cerebral parenchyma injury and will induce substantial alterations in the nature of glial cells. Injury-induced augmentation of glial cell activity and subsequent cross-interactions between glia and neurons are inevitable to some degree. Yes, glial cells respond to injuries. If one compares this response to a "scream," and responses during normal interactions between glia and neurons to a "whisper," then the most intriguing scientific phenomenon for glia researchers is the "whisper" being washed out by the "scream". To date, there is no definitive evidence indicating responses to injury are extensive and normal responses are imperceptible. However, glia researchers need to implant functional molecules into glial cells like a "spy" to extract information and to alert them of any tiny response in glial cells. Using genetically modified mice, functional molecules can be expressed specifically in glial cells without injury. Furthermore, it is desirable that outcomes of the manipulation is extracted without injury. I believe that only through these types of efforts we can understand the glial cell function. I would like to emphasize that expression of functional probes in sufficient amounts in cell-type specific manner is the first step toward promoting glial cell research, and knockin-mediated enhanced gene expression-tet system (KENGE-tet) provides a strategy for achieving this. The second step is that we challenge glia to unveil overlooked their function by taking advantage of sufficient probe expression. | | | |
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