大腦和脊髓一旦發(fā)生損傷,，那么這種損傷通常是永久性的,，因?yàn)槭艿綋p傷的神經(jīng)纖維(軸突)無(wú)法再生。但最近,，美國(guó)波士頓兒童醫(yī)院的一項(xiàng)關(guān)于老鼠的研究發(fā)現(xiàn),，刪除模式老鼠基因組中能抑制生長(zhǎng)因子的一個(gè)基因，將能使軸突再次形成,。這項(xiàng)研究發(fā)表在12月10日Neuron雜志上,。
此前，Zhigang He及其同事利用遺傳技術(shù)刪除了老鼠視網(wǎng)膜神經(jīng)節(jié)細(xì)胞內(nèi)生長(zhǎng)通路——mTOR通路的兩個(gè)抑制因子,。他們隨后發(fā)現(xiàn),，這兩個(gè)抑制因子被刪除后，老鼠大腦內(nèi)受損的軸突能夠快速再生,，但對(duì)為受損的軸突沒(méi)有影響,，這表明，損傷能夠誘導(dǎo)軸突再生,。
在這項(xiàng)新的研究中,，該課題的研究人員對(duì)老鼠采用了第二套遺傳技術(shù)，他們刪除了老鼠視網(wǎng)膜神經(jīng)節(jié)細(xì)胞的炎癥信號(hào)——SOCS3的抑制因子,，結(jié)果發(fā)現(xiàn)損傷后軸突又開(kāi)始生長(zhǎng),，并且生長(zhǎng)最明顯的時(shí)期發(fā)生在損傷后一周，此時(shí)也是mTOR通路的信號(hào)被重新激活的時(shí)期,。
此外,，課題組還發(fā)現(xiàn)視網(wǎng)膜內(nèi)另一種生長(zhǎng)因子——睫狀神經(jīng)營(yíng)養(yǎng)因子(ciliary neurotrophic factor,CNTF)也顯著增加。當(dāng)CNTF直接作用于眼睛內(nèi)，神經(jīng)元軸突的生長(zhǎng)速度甚至快于當(dāng)SOCS3被刪除后的軸突的生長(zhǎng)速度,。但如果SOCS3未被刪除,，那么老鼠視網(wǎng)膜內(nèi)CNTF增加的速度十分緩慢。
據(jù)He介紹,，之前也有科學(xué)家測(cè)試過(guò)CNTF及其他細(xì)胞因子對(duì)促進(jìn)軸突生長(zhǎng)的影響,，但都未成功。現(xiàn)在看來(lái),，這都是由于受到SOCS3的負(fù)調(diào)控機(jī)制的影響,。因此，通過(guò)某些小分子化合物或RNA干擾技術(shù)抑制SOCS3,，或許可以使這些細(xì)胞因子發(fā)揮功能,。
課題組還發(fā)現(xiàn)還可以通過(guò)另一條途徑促進(jìn)軸突再生，即直接刺激抑制SOCS3的信號(hào)通路JAK/STAT,。（生物谷Bioon.com）
神經(jīng)再生與修復(fù)研究：
PNAS：氨基酸可增強(qiáng)腦外傷恢復(fù)
Nature Neuroscience：嗅球中神經(jīng)干細(xì)胞可修復(fù)大腦損傷
J. Cell. Biochem.：人類(lèi)毛囊干細(xì)胞可修復(fù)神經(jīng)
PLoS ONE：重組人神經(jīng)生長(zhǎng)因子可用于神經(jīng)修復(fù)
生物谷推薦原始出處：
Neuron, Volume 64, Issue 5, 617-623, 10 December 2009 doi:10.1016/j.neuron.2009.11.021
SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo
Patrice D. Smith1, 2, 3, Fang Sun1, 3, Kevin Kyungsuk Park1, Bin Cai1, Chen Wang1, Kenichiro Kuwako1, Irene Martinez-Carrasco1, Lauren Connolly1 and Zhigang He1, ,
1 F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
2 Institute of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada
Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.
