Laviola Giovanni, Rea Monica, Morley-Fletcher Sara, Di Carlo Simonetta, Bacosi Antonella, De Simone Roberta, Bertini Mario, Pacifici Roberta
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Viale Regina Elena, 299, I-00161 Roma, Italy.
Eur J Neurosci. 2004 Sep;20(6):1655-64. doi: 10.1111/j.1460-9568.2004.03597.x.
The capacity of an early environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. Pregnant Sprague-Dawley rats underwent three 45-min sessions per day of prenatal restraint stress (PS) on gestation days 11-21, and their offspring were assigned to either an enriched-environment or standard living cages throughout adolescence [postnatal days (pnd) 22-43]. Juvenile rats from stressed pregnancies had a prominent depression of affiliative/playful behaviour and of basal circulating CD4 T lymphocytes, CD8 T lymphocytes and T4/T8 ratio. They also showed increased emotionality and spleen and brain frontal cortex levels of pro-inflammatory interleoukin-1beta (IL-1beta) cytokine. A more marked response to cyclophosphamide (CPA: two 2 mg/kg IP injections) induced immunosuppression was also found in prenatal stressed rats. Enriched housing increased the amount of time adolescent PS rats spent in positive species-typical behaviours (i.e. play behaviour), reduced emotionality and reverted most of immunological alterations. In addition to its effects in PS rats, enriched housing increased anti-inflammatory IL-2 and reduced pro-inflammatory IL-1beta production by activated splenocytes, also producing a marked alleviation of CPA-induced immune depression. In the brain, enriched housing increased IL-1beta values in hypothalamus, while slightly normalizing these values in the frontal cortex from PS rats. This is a first indication that an environmental intervention, such as enriched housing, during adolescence can beneficially affect basal immune parameters and rats response to both early stress and drug-induced immunosuppression.
研究了早期环境干预对缓解应激妊娠所导致的行为和免疫功能障碍的能力。将妊娠的斯普拉格-道利大鼠在妊娠第11至21天每天进行3次,每次45分钟的产前束缚应激(PS),其后代在整个青春期(出生后第22至43天)被分配到丰富环境或标准生活笼中。应激妊娠的幼年大鼠在社交/玩耍行为以及基础循环CD4 T淋巴细胞、CD8 T淋巴细胞和T4/T8比值方面有明显降低。它们还表现出情绪性增加以及脾脏和脑额叶皮质中促炎细胞因子白细胞介素-1β(IL-1β)水平升高。在产前应激大鼠中还发现对环磷酰胺(CPA:两次腹腔注射2mg/kg)诱导的免疫抑制有更明显的反应。丰富的饲养环境增加了青春期PS大鼠用于积极的典型物种行为(即玩耍行为)的时间,降低了情绪性,并逆转了大部分免疫改变。除了对PS大鼠的影响外,丰富的饲养环境还增加了抗炎性IL-2的产生,并减少了活化脾细胞产生的促炎性IL-1β,同时也显著减轻了CPA诱导的免疫抑制。在大脑中,丰富的饲养环境增加了下丘脑的IL-1β值,同时使PS大鼠额叶皮质中的这些值略有恢复正常。这首次表明,青春期的环境干预,如丰富的饲养环境,可以有益地影响基础免疫参数以及大鼠对早期应激和药物诱导的免疫抑制的反应。