Liu Wensheng, Pappas George D, Carter C Sue
Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor Street, Chicago, IL 60612, USA.
Neurol Res. 2005 Jun;27(4):339-45. doi: 10.1179/016164105X35602.
Both oxytocin (OT) and reelin are particularly significant during development and the absence of either may interfere with normal brain development. In addition, reelin is critical to the development of the GABAergic system and GABA modulates the release of OT. Availability of the reelin haploinsufficient (+/-) reeler mouse (HRM) provides a model for examining the role of reelin in the development of the OT system and especially in the expression of the OT receptor (OTR).
In this study we used immunocytochemistry and in situ hybridization in HRM versus wild-type (+/-) mice (WTM) to quantify OTR abundance in regions of the brain cortex.
Our findings reveal that the oxytocin receptor (OTR), measured either by immunohistochemistry or in situ hybridization, is significantly lower in HRM. Areas showing significant deficits included the piriform cortex, neocortex, retrosplenial cortex and certain regions of the hippocampus.
Both reelin and OT play a role in regulating affect and mood. Down-regulation of reelin has been strongly correlated with schizophrenia and it is proposed that HRM may serve as a model for neural deficits seen in both schizophrenia and autism. We report that HRM show regionally specific reductions in OTRs, especially in cortical areas, which previously have been implicated in social memory and cognitive functions. These findings offer support for the more general hypothesis that down-regulation of reelin, of either genetic or epigenetic origin, through associated reductions in the OTRs, contributes to the deficiencies in social behavior that are characteristic of both schizophrenia and autism.
催产素（OT）和瑞连蛋白在发育过程中都尤为重要，二者中任何一种缺失都可能干扰大脑正常发育。此外，瑞连蛋白对γ-氨基丁酸（GABA）能系统的发育至关重要，且GABA可调节OT的释放。瑞连蛋白单倍剂量不足（+/-）的reeler小鼠（HRM）为研究瑞连蛋白在OT系统发育尤其是OT受体（OTR）表达中的作用提供了一个模型。
在本研究中，我们对HRM和野生型（+/-）小鼠（WTM）使用免疫细胞化学和原位杂交技术，以量化大脑皮质区域中OTR的丰度。
我们的研究结果显示，无论是通过免疫组织化学还是原位杂交测量，HRM中的催产素受体（OTR）均显著降低。显示出明显缺陷的区域包括梨状皮质、新皮质、压后皮质和海马体的某些区域。
瑞连蛋白和OT在调节情感和情绪方面均发挥作用。瑞连蛋白的下调与精神分裂症密切相关，有人提出HRM可作为精神分裂症和自闭症中所见神经缺陷的模型。我们报告称，HRM的OTR在区域上有特异性减少，尤其是在皮质区域，这些区域先前与社会记忆和认知功能有关。这些发现为更普遍的假设提供了支持，即无论是遗传还是表观遗传起源的瑞连蛋白下调，通过OTR的相关减少，导致了精神分裂症和自闭症所特有的社会行为缺陷。
