Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse.

Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse.
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reelin补充恢复了杂合子卷轴小鼠中的感觉运动门控,突触可塑性和关联学习缺陷。

DOI:
10.1177/0269881112463468
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发表时间:
2013-04
期刊:
Journal of psychopharmacology (Oxford, England)
影响因子:
--
通讯作者:
Weeber EJ
Weeber EJ
中科院分区:
其他
文献类型:
--
作者:
Rogers JT;Zhao L;Trotter JH;Rusiana I;Peters MM;Li Q;Donaldson E;Banko JL;Keenoy KE;Rebeck GW;Hoe HS;D'Arcangelo G;Weeber EJ

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脂蛋白受体配体 Reelin 对于正常突触可塑性、树突形态发生以及学习和记忆过程非常重要。杂合 reeler 小鼠 (HRM) 显示出许多与精神分裂症相关的神经解剖学、生化和行为特征。 HRM 显示出微妙的形态缺陷,包括树突棘密度降低、突触可塑性改变以及联想学习和记忆以及前脉冲抑制的行为缺陷。目前的研究验证了这样的假设:体内 Reelin 水平升高可以挽救与 HRM 相关的突触和行为表型。我们证明,单次体内注射 Reelin 会增加 GAD67 表达并改变树突棘形态。与此同时,我们观察到海马突触功能以及联想学习和记忆的增强。 Reelin 补充剂还可以增强预脉冲抑制。这些结果表明,HRM 的特征与精神分裂症中观察到的特征相似,对 Reelin 水平敏感,并且可以通过补充男性和女性成人的 Reelin 来改变。
The lipoprotein receptor ligand Reelin is important for the processes of normal synaptic plasticity, dendritic morphogenesis, and learning and memory. Heterozygous reeler mice (HRM) show many neuroanatomical, biochemical, and behavioral features that are associated with schizophrenia. HRM show subtle morphological defects including reductions in dendritic spine density, altered synaptic plasticity and behavioral deficits in associative learning and memory and pre-pulse inhibition. The present studies test the hypothesis that in vivo elevation of Reelin levels can rescue synaptic and behavioral phenotypes associated with HRM. We demonstrate that a single in vivo injection of Reelin increases GAD67 expression and alters dendritic spine morphology. In parallel we observed enhancement of hippocampal synaptic function and associative learning and memory. Reelin supplementation also increases pre-pulse inhibition. These results suggest that characteristics of HRM, similar to those observed in schizophrenia, are sensitive to Reelin levels and can be modified with Reelin supplementation in male and female adults.
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