Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.

Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.
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DOI:
10.1371/journal.pone.0063824
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Gammie SC
Gammie SC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Eisinger BE;Zhao C;Driessen TM;Saul MC;Gammie SC

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协调基因表达的变化,整个中枢神经系统需要产生哺乳动物的母体表型。外侧隔(LS)是一个大脑区域,与孕产妇护理方面的关键参与,我们最近研究了基因表达的整个隔膜(LS和内侧隔)在选择性繁殖的母鼠。在这里,我们通过以下方式扩展了先前的研究:1)仅对处女和产后小鼠的LS进行微阵列分析,2)使用远交小鼠,3)评估感觉输入对基因表达变化的作用。鉴定了与神经元信号传导相关的基因的大规模变化,包括四个GABAA受体亚基。母体LS中α4和δ亚基下调,可能反映了突触外、神经类固醇敏感的α4/δ受体亚型的减少。相反,亚基ε和θ在母体LS中增加。15个K+通道相关基因表达改变,多巴胺受体Drd 1a和Drd 2(均下调)、下丘脑泌素受体1(Hcrtr 1)、κ阿片受体1(Oprk 1)和瞬时受体电位通道4(Trpc 4)也发生了改变。与发育过程或细胞分化相关的大量基因的表达也在产后LS中改变,包括趋化因子(C-X-C)基序配体12(Cxcl 12)、脂肪酸结合蛋白7(Fabp 7)、质膜蛋白脂质(Pllp)和细胞因子信号传导抑制因子2(Socs 2)。与焦虑有关的其他基因,如谷胱甘肽还原酶(Gsr),表现出表达改变。通路分析还确定了与环核苷酸代谢、染色质结构和Ras基因家族相关的基因的变化。研究人员发现,幼犬的感官存在有助于改变所有类别中一部分基因的表达。这项研究表明,在神经元信号和可能的神经元和/或神经胶质细胞的终末分化的大的变化在产生母体状态中发挥重要作用。
Coordinated gene expression changes across the CNS are required to produce the mammalian maternal phenotype. Lateral septum (LS) is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum) in selectively bred maternal mice. Here, we expand on the prior study by 1) conducting microarray analysis solely on LS in virgin and postpartum mice, 2) using outbred mice, and 3) evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including four GABAA receptor subunits. Subunits α4 and δ were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive α4/δ containing receptor subtype. Conversely, subunits ε and θ were increased in maternal LS. Fifteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated), hypocretin receptor 1 (Hcrtr1), kappa opioid receptor 1 (Oprk1), and transient receptor potential channel 4 (Trpc4). Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C) motif ligand 12 (Cxcl12), fatty acid binding protein 7 (Fabp7), plasma membrane proteolipid (Pllp), and suppressor of cytokine signaling 2 (Socs2). Additional genes that are linked to anxiety, such as glutathione reductase (Gsr), exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.
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