Llorente Ricardo, Llorente-Berzal Alvaro, Petrosino Stefania, Marco Eva-María, Guaza Carmen, Prada Carmen, López-Gallardo Meritxell, Di Marzo Vincenzo, Viveros María-Paz
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Madrid, Spain.
Dev Neurobiol. 2008 Sep 15;68(11):1334-47. doi: 10.1002/dneu.20666.
Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days (PND) 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. These behavioral impairments may be related to neuronal loss in the hippocampus triggered by elevated glucocorticoids. Furthermore, our previous data suggested functional relationships between MD stress and the endocannabinoid system. In this study, we addressed the effects of MD on hippocampal glial cells and the possible relationship with changes in plasma corticosterone (CORT) levels. In addition, we investigated the putative involvement of the endocannabinoid system by evaluating (a) the effects of MD on hippocampal levels of endocannabinoids (b) The modulation of MD effects by two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin (AA-5-HT), and the endocannabinoid reuptake inhibitor, OMDM-2. Drug treatments were administered once daily from PND 7 to PND 12 at a dose of 5 mg/kg, and the animals were sacrificed at PND 13. MD induced increased CORT levels in both genders. MD males also showed an increased number of astrocytes in CA1 and CA3 areas and a significant increase in hippocampal 2-arachidonoylglycerol. The cannabinoid compounds reversed the endocrine and cellular effects of maternal deprivation. We provide direct evidence for gender-dependent cellular and biochemical effects of MD on developmental hippocampus, including changes in the endocannabinoid system.
成年动物经历单次长时间的母婴分离（MD）（产后第9 - 10天，持续24小时）后会出现行为改变，类似于精神分裂症的特定症状。这些行为损伤可能与糖皮质激素升高引发的海马体神经元损失有关。此外，我们之前的数据表明MD应激与内源性大麻素系统之间存在功能关系。在本研究中，我们探讨了MD对海马体神经胶质细胞的影响以及与血浆皮质酮（CORT）水平变化的可能关系。此外，我们通过评估（a）MD对海马体内源性大麻素水平的影响，（b）两种内源性大麻素失活抑制剂，即脂肪酸酰胺水解酶抑制剂N - 花生四烯酰 - 5 - 羟色胺（AA - 5 - HT）和内源性大麻素再摄取抑制剂OMDM - 2对MD效应的调节作用，来研究内源性大麻素系统的假定参与情况。从产后第7天到第12天，每天以5mg/kg的剂量给药一次，在产后第13天处死动物。MD导致两性的CORT水平升高。MD雄性动物在CA1和CA3区域的星形胶质细胞数量也增加，海马体中2 - 花生四烯酸甘油酯显著增加。大麻素化合物逆转了母婴分离的内分泌和细胞效应。我们提供了直接证据，证明MD对发育中的海马体具有性别依赖性的细胞和生化效应，包括内源性大麻素系统的变化。
