Altered postnatal cell proliferation in brains of mouse pups prenatally exposed to IgG from mothers of children with autistic disorder.

Altered postnatal cell proliferation in brains of mouse pups prenatally exposed to IgG from mothers of children with autistic disorder.
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DOI:
10.4137/jen.s12979
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发表时间:
2013
影响因子:
--
通讯作者:
Singer HS
Singer HS
中科院分区:
其他
文献类型:
--
作者:
Kadam SD;French BM;Kim ST;Morris-Berry CM;Zimmerman AW;Blue ME;Singer HS

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在自闭症儿童(MCAD)的母亲中发现的自身抗体,当被动转移到怀孕的小鼠时,会导致幼年和成年后代的行为改变。本研究的目的是确定妊娠期间腹腔注射MCAD-IgG是否会影响P7后代的出生后细胞增殖和存活。每日向C57 BL/J6妊娠母鼠(妊娠第E13-E18天)注射来自未受影响儿童(MUC)母亲的合并MCAD-IgG或IgG或磷酸盐缓冲盐水。MCAD-IgG暴露显著增加了脑室下和颗粒下区的细胞增殖。相比之下,与MUC和PBS注射小鼠相比,P1上的BrdU标记细胞和存活至P7的细胞(P1产生的细胞)显示MCAD小鼠额叶和顶叶皮质2-4层的细胞密度降低。总之,与MUC和PBS相比,P7时细胞增殖的显著增加和P1产生的细胞密度的降低区分了子宫内暴露于MCAD。
Auto antibodies found in the mothers of children with autistic disorder (MCAD) when passively transferred to pregnant mice cause behavioral alterations in juvenile and adult offspring. The goal of this study was to identify whether intraperitoneal injection of MCAD-IgG during gestation affected postnatal cell proliferation and survival in P7 offspring. Pooled MCAD-IgG or IgG from mothers of unaffected children (MUC) or phosphate-buffered saline was injected daily into C57BL/J6 pregnant dams (gestational days E13–E18). MCAD-IgG exposure significantly increased cell proliferation in the subventricular and subgranular zones. In contrast, BrdU-labeled cells on P1 and surviving until P7 (P1-generated cells) showed reduced cell densities in layers 2–4 of frontal and parietal cortices of MCAD mice compared to those in MUC and PBS-injected mice. In conclusion, significant increases in cell proliferation at P7 and reduced densities of P1-generated cells distinguish in utero exposure to MCAD compared to MUC and PBS.