2012年10月27日 訊 /生物谷BIOON/ --由美國加州大學(xué)戴維斯分校神經(jīng)科學(xué)中心科研人員最新一項研究證實：孕鼠免疫系統(tǒng)可引起后代大腦的變化,。這一發(fā)現(xiàn)可能幫助研究人員更好地了解如神經(jīng)發(fā)育障礙,、精神分裂癥和自閉癥的發(fā)病原因,。相關(guān)研究結(jié)果發(fā)表在Brain, Behavior and Immunity雜志上,。
神經(jīng)生物學(xué)家Kimberley McAllister給予孕鼠可以模仿病毒感染的化學(xué)物質(zhì),。然后,，測量出生后的小鼠大腦中23種不同細(xì)胞因子的水平,。細(xì)胞因子是免疫信號分子,，在體內(nèi)激發(fā)防御感染機制抵抗病毒等,。細(xì)胞因子也出現(xiàn)在小鼠正常大腦發(fā)育過程中,。與正常鼠相比，給予孕鼠化學(xué)物質(zhì)所誕生的后代,，小鼠幾個大腦區(qū)域的細(xì)胞因子表現(xiàn)出不同的模式,。
在早期的實驗中可以看出，化學(xué)物質(zhì)處理的小鼠的后代會表現(xiàn)出自閉癥和精神分裂癥等行為,。據(jù)了解,，病毒觸發(fā)孕婦免疫系統(tǒng)時,，細(xì)胞因子會越過胎盤進入后代。在此之前,，上述機制只在感染發(fā)生時存在,。研究人員希望看到給予化學(xué)物質(zhì)的小鼠大腦中高水平的細(xì)胞因子。他們驚訝地發(fā)現(xiàn),，母親的免疫信號分子持續(xù)在小鼠大腦中存在,。
值得注意的是，這些蛋白質(zhì)的變化方向是與預(yù)期相反的,。加州大學(xué)戴維斯分校研究員Judy Van de Water表示免疫系統(tǒng)對神經(jīng)發(fā)育障礙的作用是一個有趣的發(fā)現(xiàn),，需要作進一步研究調(diào)查。但很明顯,，母體的免疫反應(yīng)可影響后代大腦的發(fā)育和免疫系統(tǒng),，但其中也有可能存在額外的風(fēng)險因素，導(dǎo)致小鼠出生后易患孤獨癥和精神分裂癥,。研究人員表示如果發(fā)現(xiàn)細(xì)胞因子的變化對神經(jīng)發(fā)育障礙發(fā)揮了重要作用,，那么有可能針對這些細(xì)胞因子來恢復(fù)大腦的正常發(fā)育。（生物谷：Bioon.com）
doi:10.1016/j.bbi.2012.07.008
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Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development
Paula A. Garaya, Elaine Y. Hsiaob, Paul H. Pattersonb, A.K. McAllistera, ,
Maternal infection is a risk factor for autism spectrum disorder (ASD) and schizophrenia (SZ). Indeed, modeling this risk factor in mice through maternal immune activation (MIA) causes ASD- and SZ-like neuropathologies and behaviors in the offspring. Although MIA upregulates pro-inflammatory cytokines in the fetal brain, whether MIA leads to long-lasting changes in brain cytokines during postnatal development remains unknown. Here, we tested this possibility by measuring protein levels of 23 cytokines in the blood and three brain regions from offspring of poly(I:C)- and saline-injected mice at five postnatal ages using multiplex arrays. Most cytokines examined are present in sera and brains throughout development. MIA induces changes in the levels of many cytokines in the brains and sera of offspring in a region- and age-specific manner. These MIA-induced changes follow a few, unexpected and distinct patterns. In frontal and cingulate cortices, several, mostly pro-inflammatory, cytokines are elevated at birth, followed by decreases during periods of synaptogenesis and plasticity, and increases again in the adult. Cytokines are also altered in postnatal hippocampus, but in a pattern distinct from the other regions. The MIA-induced changes in brain cytokines do not correlate with changes in serum cytokines from the same animals. Finally, these MIA-induced cytokine changes are not accompanied by breaches in the blood–brain barrier, immune cell infiltration or increases in microglial density. Together, these data indicate that MIA leads to long-lasting, region-specific changes in brain cytokines in offspring—similar to those reported for ASD and SZ—that may alter CNS development and behavior.
