論文

国際誌
2022年2月2日

Involvement of Denervated Midbrain-Derived Factors in the Formation of Ectopic Cortico-Mesencephalic Projection after Hemispherectomy.

The Journal of neuroscience : the official journal of the Society for Neuroscience
  • Leechung Chang
  • ,
  • Mayuko Masada
  • ,
  • Masami Kojima
  • ,
  • Nobuhiko Yamamoto

42
5
開始ページ
749
終了ページ
761
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1523/JNEUROSCI.1371-21.2021

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain, but the molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at early developmental stages using mice of either sex, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by glial cells. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit β three or neurotrophic receptor tyrosine kinase 2 (also known as TrkB) was knocked out. Overall, the present study suggests that denervated midbrain-derived glial factors contribute to lesion-induced remodeling of the cortico-mesencephalic projection via these receptors.SIGNIFICANCE STATEMENT After brain injury, compensatory neural circuits are established that contribute to functional recovery. However, little is known about the intrinsic mechanism that underlies the injury-induced remodeling. We found that after unilateral cortical ablation expression of axon-growth promoting factors is elevated in the denervated midbrain and is involved in the formation of ectopic axonal projection from the intact cortex. Evidence further demonstrated that these factors are expressed by astrocytes and microglia, which are activated in the denervated midbrain. Thus, our present study provides a new insight into the mechanism of lesion-induced axonal remodeling and further therapeutic strategies after brain injury.

リンク情報
DOI
https://doi.org/10.1523/JNEUROSCI.1371-21.2021
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34887319
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808734
ID情報
  • DOI : 10.1523/JNEUROSCI.1371-21.2021
  • PubMed ID : 34887319
  • PubMed Central 記事ID : PMC8808734

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