Research press release


Nature Neuroscience

Genes regulating neuronal sprouting after stroke

脳卒中後の回復に伴う成長を示す神経細胞と示さない神経細胞の遺伝子発現の違いが、Nature Neuroscience(電子版)の論文で報告されている。この発見は、ヒトの脳卒中の新たな治療標的を特定する可能性を秘めている。


T Carmichaelらは、脳卒中を起こしたラットの同一個体から、発芽した神経細胞と発芽していない神経細胞を選択的に標識し単離できる方法を開発した。次に、これら2種類の神経群の遺伝子発現プロファイルを比較し、違いを同定した。ヒトの脳卒中患者は高齢者が大多数であり、また脳卒中は加齢性疾患なので、若年ラットと老年ラットの遺伝子発現の違いを比較したところ、多くの有意な差を発見した。


Gene expression differences between neurons that show recovery-associated growth after stroke and neurons that don’t show such growth are reported in a study published online this week in Nature Neuroscience. These findings have the potential to identify novel therapeutic targets for the treatment of stroke in humans.

Recovery from stroke had been associated with the brain’s ability to reorganize by having spared regions assume functions carried out by the compromised tissue. This reorganization is thought to be sub-served, in part, by axonal growth or “sprouting” of spared neurons, which allows them to make new connections in the recovering brain. However, only a subset of spared neurons show sprouting and what makes these neurons “special” is unknown.

Thomas Carmichael and colleagues developed a technique that allowed them to selectively label and then isolate sprouting and non-sprouting neurons from the same rats after stroke. They then compared gene expression profiles of these two neuronal groups to identify differences. Because the majority of human stroke victims are older adults, they also compared gene expression differences between young and aged rats. Because stroke is an age-related disease, they also compared gene expression differences between young and aged rats and found a number of significant differences.

As proof of concept, the authors selected a set of the genes which were highly activated in sprouting neurons from aged rats and studied these further. They report that an epigenetic regulatory protein and a growth factor acted to promote sprouting, whereas up-regulated inhibitory myelin receptors acted to limit sprouting.

doi: 10.1038/nn.2674

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