Stem Cells:星形膠質細胞控制神經幹細胞產生的新神經元

神經幹細胞分化圖。

2012年8月28日 訊 /生物谷BIOON/ --瑞典哥德堡大學薩爾格學院(Sahlgrenska Academy)研究員Milos Pekny教授領導的一個研究小組在Stem Cells期刊上發表了一篇關於控制大腦中新神經元產生的分子機制方面的研究論文。

星形膠質細胞是在中樞神經系統發揮著很多功能的細胞，這些功能包括控制神經元突觸和血液流動，或者大腦對神經外傷或中風的反應。

減少大腦組織損傷

Pekny教授實驗室與合作人員開展研究，並在早期證實星形膠質細胞降低中風發作後大腦組織遭受的損傷，和通過調節星形膠質細胞的活性能夠極大地改善移植的神經幹細胞的整合。

產生新的神經元

在當前這項研究中，研究人員證實星形膠質細胞如何控制大腦中新神經元的產生。

Pekny教授說，「在大腦中，星形膠質細胞控制著神經幹細胞形成新的神經元的數量和成功整合到現存的神經元網絡的神經元數量。為完成這種控制，星形膠質細胞分泌特異性的分子以及通過人們很少了解的與幹細胞之間發生直接的細胞間相互作用。」

重要的調劑物

Pekny教授說，「星形膠質細胞與神經幹細胞之間發生物理接觸，並且我們證實它們通過Notch通路給幹細胞發生信號從而保持較低的新神經元產生率。我們還證實星形膠質細胞中間纖維系統是這種過程的一種重要的調節物。它似乎表明星形膠質細胞中間纖維能夠被用來一種靶標來增加新神經元的產生率。」

用於未來療法的靶標

Pekny教授說，「我們正開始理解控制神經元發生背後的一些細胞機制和分子機制。神經發生是大腦可塑性組分之一，其中大腦可塑性在學習過程和大腦損傷或中風發作之後的恢復中發揮著作用。這項研究有助於我們理解人們在未來如何能夠在治療上促進可塑性和再生反應。」(生物谷Bioon.com)

本文編譯自Astrocytes Control the Generation of New Neurons from Neural Stem Cells

Astrocytes Negatively Regulate Neurogenesis through the Jagged1-Mediated Notch Pathway

Richard Virgen-Slanea, Janet M. Rozovicsa, Kerry D. Fitzgeralda, Tuan Ngob, Wayne Choub, Gerbrand J. van der Heden van Noortc, Dmitri V. Filippovc, Paul D. Gershonb, and Bert L. Semler

Astrocytes participate actively in brain development, regulation of the mature CNS, and brain plasticity. They are important regulators of the local environment in adult neurogenic niches through the secretion of diffusible morphogenic factors, such as Wnts. Astrocytes control the neurogenic niche also through membrane-associated factors, however the identity of these factors and the mechanisms involved are largely unknown. In this study, we sought to determine the mechanisms underlying our earlier finding of increased neuronal differentiation of neural progenitor cells when co-cultured with astrocytes lacking glial fibrillary acidic protein and vimentin (GFAP−/−Vim−/−). We used primary astrocyte and neurosphere co-cultures to demonstrate that astrocytes inhibit neuronal differentiation through a cell-cell contact. GFAP−/−Vim−/− astrocytes showed reduced endocytosis of Notch ligand Jagged1, reduced Notch signaling and increased neuronal differentiation of neurosphere cultures. This effect of GFAP−/−Vim−/− astrocytes was abrogated in the presence of immobilized Jagged1 in a manner dependent on the activity of gamma-secretase. Lastly, we used GFAP−/−Vim−/− mice to show that in the absence of GFAP and vimentin, hippocampal neurogenesis under basal conditions as well as after injury is increased. We conclude that astrocytes negatively regulate neurogenesis through the Notch pathway, and endocytosis of Notch ligand Jagged1 in astrocytes and Notch signaling from astrocytes to neural stem/progenitor cells depends on the intermediate filament proteins GFAP and vimentin.