加州大學(xué)戴維斯分?？茖W(xué)家的一項(xiàng)最新研究表明,，一種免疫系統(tǒng)蛋白分子能調(diào)控大腦神經(jīng)元之間突觸連接的數(shù)量。這也顯示出,，在人們的免疫能力,、感染疾病和精神狀態(tài)，如精神分裂,、孤獨(dú)癥之間可能存在著某種關(guān)聯(lián),。相關(guān)研究發(fā)表在2月27日出版的《自然·神經(jīng)科學(xué)》上。
加州大學(xué)戴維斯分校神經(jīng)病與神經(jīng)生物學(xué),、生理與行為學(xué)院副教授金伯利·麥卡利斯特解釋說(shuō),，精神分裂、孤獨(dú)癥以及其他精神錯(cuò)亂等神經(jīng)疾病與腦神經(jīng)連接的改變有關(guān),，這些改變影響了大腦正確處理信息的能力,。“某些免疫基因和免疫失調(diào)也和孤獨(dú)癥和精神分裂有關(guān)系，根據(jù)我們的研究,，大腦中免疫分子的形成可能會(huì)改變腦神經(jīng)的連通性,。”
他們研究的是一種名為主要組織相容性復(fù)合物I型（MHC type I）的蛋白質(zhì)。10年前人們就發(fā)現(xiàn),，在出生后較晚時(shí)的大腦發(fā)育關(guān)鍵期,，MHC-I型蛋白質(zhì)與突觸連接的消除有關(guān)。而新研究發(fā)現(xiàn)了MHC-I型蛋白質(zhì)的另一項(xiàng)功能,，它還能在出生后早期的大腦發(fā)育期間建立起神經(jīng)元的連接,。
無(wú)論是嚙齒類動(dòng)物還是人類，MHC-Ⅰ型蛋白質(zhì)在每個(gè)個(gè)體之間都不同,，免疫系統(tǒng)以此來(lái)區(qū)分出“自己”和“異己”,，從而在防御癌癥、抵抗病毒感染以及排斥移植器官等方面發(fā)揮著重要作用,。
研究小組在出生后較早發(fā)育期的小鼠年輕的腦細(xì)胞中發(fā)現(xiàn)了MHC-I型分子,，并對(duì)其功能進(jìn)行了檢測(cè)，同時(shí)研究在小鼠神經(jīng)元表面MHC-I型分子的水平不同會(huì)對(duì)神經(jīng)元造成何種影響,。他們發(fā)現(xiàn),，當(dāng)腦細(xì)胞表面這種分子密度增加時(shí)，神經(jīng)元與相鄰腦細(xì)胞的突觸連接就會(huì)下降,；反過(guò)來(lái),，當(dāng)分子水平下降，突觸連接會(huì)增加,。
“由于MHC-I型蛋白質(zhì)的作用,，突觸密度受到了影響。”麥卡利斯特解釋說(shuō),，這些免疫蛋白不僅能調(diào)控突觸密度,，它們還能平衡年輕腦細(xì)胞的興奮和抑制，這種性質(zhì)是大腦信息處理和可塑性的關(guān)鍵,。神經(jīng)活躍性調(diào)控著腦中MHC-I型蛋白質(zhì)的表達(dá),，而MHC-I型蛋白質(zhì)也調(diào)控著神經(jīng)活躍性轉(zhuǎn)變?yōu)橥挥|連接的能力。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature Neuroscience doi:10.1038/nn.2764
MHCI negatively regulates synapse density during the establishment of cortical connections
Marian W Glynn,1, 2 Bradford M Elmer,1, 3 Paula A Garay,1, 3 Xiao-Bo Liu,1 Leigh A Needleman,1 Faten El-Sabeawy1 & A Kimberley McAllister1
Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. We found that MHCI also negatively regulates the density and function of cortical synapses during their initial establishment both in vitro and in vivo. MHCI molecules are expressed on cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increased glutamatergic and GABAergic synapse density, whereas overexpression decreased it. In vivo, synapse density was higher throughout development in β2m?/? mice. MHCI also negatively regulated the strength of excitatory, but not inhibitory, synapses and controlled the balance of excitation and inhibition onto cortical neurons. sMHCI levels were modulated by activity and were necessary for activity to negatively regulate glutamatergic synapse density. Finally, acute changes in sMHCI and activity altered synapse density exclusively during early postnatal development. These results identify a previously unknown function for immune proteins in the negative regulation of the initial establishment and function of cortical connections.
