近期，美國加州大學圣地亞哥分校（UC San Diego）研究人員首次實現(xiàn)大鼠腦損傷部位神經(jīng)軸突的再生,。加州大學圣地亞哥分校神經(jīng)修復中心主任Mark Tuszynski 表示,，該發(fā)現(xiàn)標志著一類神經(jīng)纖維系統(tǒng)——皮質(zhì)脊髓運動軸突（orticospinal motor axon）再生方法的建立，而這類軸突的再生是脊髓損傷病人實現(xiàn)隨意運動的關(guān)鍵一步,。該研究發(fā)表在4月6日的Proceedings of the National Academy of Sciences雜志上,。該研究得到美國國立衛(wèi)生研究院（NIH）、退伍軍人管理局（Veterans Administration）醫(yī)療中心等有關(guān)機構(gòu)的資助,。
神經(jīng)軸突是貫穿大腦皮層和脊髓之間神經(jīng)元的細長突出,，分布于大腦和脊髓之間，為一種關(guān)鍵類型的神經(jīng)纖維,，參與皮質(zhì)脊髓的構(gòu)成和隨意運動（voluntary movement）的實現(xiàn),。位于大腦前葉的上運動神經(jīng)元激活后，引導隨意運動的發(fā)生,，并通過其脊髓軸突傳遞到下運動神經(jīng)元,。下運動神經(jīng)元則將軸突伸展到肌肉細胞。脊髓損傷后,，沿皮質(zhì)脊髓的軸突嚴重受損,，從而導致位于損傷部位的下運動神經(jīng)元與大腦失去有效功能鏈接,。
Tuszynski 表示，此前的脊髓損傷研究證明參與隨意運動其他類型神經(jīng)纖維的再生,，但沒有明確證實皮質(zhì)脊髓系統(tǒng)的再生性,。理論上，這是由于皮質(zhì)脊髓神經(jīng)元有關(guān)軸突再生的基因表達調(diào)控能力有限,。因此,，沒有皮質(zhì)脊髓神經(jīng)軸突的再生，則不可能真正實現(xiàn)神經(jīng)系統(tǒng)的恢復,。
Tuszynski 研究小組通過遺傳工程,，使得受損神經(jīng)元過量表達一種腦源性神經(jīng)營養(yǎng)因子（BNDF）的受體蛋白trkB。隨后,，在腦損傷部位施用BNDF,。由于表達受體蛋白trkB 的神經(jīng)軸突可以對BDNF 做出有效反應(yīng)，從而實現(xiàn)收損傷部位的軸突再生,。相反,，沒有trkB 的過量表達，沒有觀察到神經(jīng)軸突再生發(fā)生,。
盡管還沒有對動物實驗中的神經(jīng)功能恢復情況進行評估,，新的研究首次證實，皮質(zhì)脊髓系統(tǒng)的再生有可能實現(xiàn),。研究人員表示,，一旦成功實現(xiàn)受損神經(jīng)元向神經(jīng)軸突和脊髓輸送這種生長因子受體，下一步工作將圍繞神經(jīng)功能修復評估展開,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS April 9, 2009, doi: 10.1073/pnas.0810624106
Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation
Edmund R. Hollis IIa, Pouya Jamshidia, Karin L?wa, Armin Blescha and Mark H. Tuszynskia,b,1
aDepartment of Neurosciences, University of California at San Diego, La Jolla, CA 92093-0626; and
bVeterans Affairs Medical Center, La Jolla, CA 92161
Abstract
Several experimental manipulations of the CNS environment successfully elicit regeneration of sensory and bulbospinal motor axons but fail to elicit regeneration of corticospinal axons, suggesting that cell-intrinsic mechanisms limit the regeneration of this critical class of motor neurons. We hypothesized that enhancement of intrinsic neuronal growth mechanisms would enable adult corticospinal motor axon regeneration. Lentiviral vectors were used to overexpress the BDNF receptor trkB in layer V corticospinal motor neurons. After subcortical axotomy, trkB transduction induced corticospinal axon regeneration into subcortical lesion sites expressing BDNF. In the absence of trkB overexpression, no regeneration occurred. Selective deletion of canonical, trkB-mediated neurite outgrowth signaling by mutation of the Shc/FRS-2 activation domain prohibited Erk activation and eliminated regeneration. These findings support the hypothesis that the refractory regenerative state of adult corticospinal axons can be attributed at least in part to neuron-intrinsic mechanisms, and that activation of ERK signaling can elicit corticospinal tract regeneration.
