研究人員已經(jīng)發(fā)現(xiàn)了使得斑馬魚的大腦能夠在其受到創(chuàng)傷性損害之后再生的機制,。與哺乳動物不同，這些在淡水中生長的小鰷魚因為腦部損傷所致的炎癥會伴有新神經(jīng)元的產(chǎn)生,。
如今,，Nikos Kyritsis及其同事展示,，在損傷反應(yīng)中，斑馬魚腦部的炎癥會激活特定的信號傳導(dǎo)分子及神經(jīng)膠質(zhì)細(xì)胞,，后者可促進(jìn)替代神經(jīng)元的生長,。研究人員在不造成損傷的情況下用藥物引發(fā)了斑馬魚腦中的炎癥并發(fā)現(xiàn)，被稱作放射狀膠質(zhì)細(xì)胞的特定細(xì)胞仍然可受到誘導(dǎo)而產(chǎn)生新的細(xì)胞,。然而,，他們說，炎癥信號受到抑制的斑馬魚則無法產(chǎn)生新的神經(jīng)元或鰭細(xì)胞,。Kyritsis和其他的研究人員發(fā)現(xiàn),，一種叫做半胱氨酰白三烯受體1——或Cystlr1的蛋白質(zhì)的表達(dá)對斑馬魚的再生過程是至關(guān)重要的。
當(dāng)他們在斑馬魚腦內(nèi)注射一種叫做LTC4的該蛋白的配體時,，研究人員觀察到,，在沒有任何炎癥時新的神經(jīng)元也會產(chǎn)生。因此,，他們鑒于這些結(jié)果提出,，在放射狀膠質(zhì)細(xì)胞內(nèi)，炎癥一定是通過與LTC4信號傳導(dǎo)級聯(lián)反應(yīng)進(jìn)行耦合才能使斑馬魚的受損神經(jīng)元重新生長,。
他們表示,，他們的發(fā)現(xiàn)可能最終會在治療創(chuàng)傷性腦損傷及神經(jīng)退行性疾病中找到治療性的應(yīng)用。（生物谷Bioon.com）
doi: 10.1126/science.1228773
PMC:
PMID:
Acute Inflammation Initiates the Regenerative Response in the Adult Zebrafish Brain
Nikos Kyritsis, Caghan Kizil, Sara Zocher, Volker Kroehne, Jan Kaslin, Dorian Freudenreich, Anne Iltzsche, Michael Brand
The zebrafish regenerates its brain after injury and hence is a useful model organism to study the mechanisms enabling regenerative neurogenesis, which is poorly manifested in mammals. Yet, the signaling mechanisms initiating such a regenerative response in fish are unknown. Using cerebroventricular microinjection of immunogenic particles and immunosuppression assays, we show that inflammation is required and sufficient for enhancing the proliferation of neural progenitors and subsequent neurogenesis by activating injury-induced molecular programs that can be observed after traumatic brain injury. We also identified the cysteinyl leukotriene signaling as an essential component of inflammation on the regenerative process of the adult zebrafish brain. Thus, our results demonstrate that in zebrafish—in contrast to mammals—inflammation is a positive regulator of neuronal regeneration in the central nervous system.
