2012年10月27日 讯 /生物谷BIOON/ --由美国加州大学戴维斯分校神经科学中心科研人员最新一项研究证实:孕鼠免疫系统可引起后代大脑的变化。这一发现可能帮助研究人员更好地了解如神经发育障碍、精神分裂症和自闭症的发病原因。相关研究结果发表在Brain, Behavior and Immunity杂志上。
神经生物学家Kimberley McAllister给予孕鼠可以模仿病毒感染的化学物质。然后,测量出生后的小鼠大脑中23种不同细胞因子的水平。细胞因子是免疫信号分子,在体内激发防御感染机制抵抗病毒等。细胞因子也出现在小鼠正常大脑发育过程中。与正常鼠相比,给予孕鼠化学物质所诞生的后代,小鼠几个大脑区域的细胞因子表现出不同的模式。
在早期的实验中可以看出,化学物质处理的小鼠的后代会表现出自闭症和精神分裂症等行为。据了解,病毒触发孕妇免疫系统时,细胞因子会越过胎盘进入后代。在此之前,上述机制只在感染发生时存在。研究人员希望看到给予化学物质的小鼠大脑中高水平的细胞因子。他们惊讶地发现,母亲的免疫信号分子持续在小鼠大脑中存在。
值得注意的是,这些蛋白质的变化方向是与预期相反的。加州大学戴维斯分校研究员Judy Van de Water表示免疫系统对神经发育障碍的作用是一个有趣的发现,需要作进一步研究调查。但很明显,母体的免疫反应可影响后代大脑的发育和免疫系统,但其中也有可能存在额外的风险因素,导致小鼠出生后易患孤独症和精神分裂症。研究人员表示如果发现细胞因子的变化对神经发育障碍发挥了重要作用,那么有可能针对这些细胞因子来恢复大脑的正常发育。(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.