Suárez Juan, Llorente Ricardo, Romero-Zerbo Silvana Y, Mateos Beatriz, Bermúdez-Silva Francisco J, de Fonseca Fernando Rodríguez, Viveros María-Paz
Laboratorio de Medicina Regenerativa, Fundación IMABIS, Hospital Carlos Haya, 29010 Málaga, Spain.
Hippocampus. 2009 Jul;19(7):623-32. doi: 10.1002/hipo.20537.
Early maternal deprivation (MD) in rats (24 h, postnatal day 9-10) is a model for neurodevelopmental stress. There are some data proving that MD affects the endocannabinoid system (ECS) in a gender-dependent manner, and that these changes may account for the proposed schizophrenia-like phenotype of MD rats. The impact of MD on cannabinoid receptor distribution in the hippocampus is unknown. The aim of this study is to evaluate the expression of CB(1) and CB(2) receptors in diverse relevant subregions (DG, CA1, and CA3) of the hippocampus in 13-day-old rats by immunohistochemistry and densitometry. MD induced a significant decrease in CB(1) immunoreactivity (more marked in males than in females), which was mainly associated with fibers in the strata pyramidale and radiatum of CA1 and in the strata oriens, pyramidale, and radiatum of CA3. In contrast, MD males and females showed a significant increase in CB(2) immunoreactivity in the three hippocampal areas analyzed that was detected in neuropil and puncta in the stratum oriens of CA1 and CA3, and in the polymorphic cell layer of the dentate gyrus. A marked sex dimorphism was observed in CA3, with females exhibiting higher CB(1) immunoreactivity than males, and in dentate gyrus, with females exhibiting lower CB(2) immunoreactivity than males. These results point to a clear association between developmental stress and dysregulation of the ECS. The present MD procedure may provide an interesting experimental model to further address the role of the ECS in neurodevelopmental mental illnesses such as schizophrenia.
大鼠早期母体剥夺（MD，出生后第9 - 10天剥夺24小时）是一种神经发育应激模型。有一些数据证明，MD以性别依赖的方式影响内源性大麻素系统（ECS），并且这些变化可能解释了MD大鼠所呈现的精神分裂症样表型。MD对海马中大麻素受体分布的影响尚不清楚。本研究的目的是通过免疫组织化学和密度测定法评估13日龄大鼠海马不同相关亚区（齿状回、CA1和CA3）中CB(1)和CB(2)受体的表达。MD导致CB(1)免疫反应性显著降低（雄性比雌性更明显），这主要与CA1的锥体层和辐射层以及CA3的原层、锥体层和辐射层中的纤维有关。相比之下，MD雄性和雌性在分析的三个海马区域中CB(2)免疫反应性显著增加，在CA1和CA3的原层神经毡和小点以及齿状回的多形细胞层中检测到。在CA3中观察到明显的性别二态性，雌性的CB(1)免疫反应性高于雄性，在齿状回中，雌性的CB(2)免疫反应性低于雄性。这些结果表明发育应激与ECS失调之间存在明显关联。目前的MD程序可能提供一个有趣的实验模型，以进一步探讨ECS在精神分裂症等神经发育性精神疾病中的作用。
