Casolini Paola, Domenici Maria Rosaria, Cinque Carlo, Alemà Giovanni Sebastiano, Chiodi Valentina, Galluzzo Mariangela, Musumeci Marco, Mairesse Jerome, Zuena Anna Rita, Matteucci Patrizia, Marano Giuseppe, Maccari Stefania, Nicoletti Ferdinando, Catalani Assia
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Faculty of Medicine, 00185 Rome, Italy.
J Neurosci. 2007 Jun 27;27(26):7041-6. doi: 10.1523/JNEUROSCI.1074-07.2007.
A growing body of evidence underscores the importance of early life events as predictors of health in adulthood. Abnormalities in maternal care or other forms of early postnatal stress induce long-term changes in behavior and influence the vulnerability to illnesses throughout life. Some of these changes may be produced by the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is invariably associated with stress. We used a model in which neonate rats are fed by mothers drinking water supplemented with 0.2 mg/ml corticosterone, the main glucocorticoid hormone in rodents. Plasma corticosterone levels increased in the dams to an extent similar to that induced by a mild stress. Corticosterone-treated dams also showed an increase in maternal care. Remarkably, adult rats that had been nursed by corticosterone-treated mothers were protected against neuronal damage and cognitive impairment produced by transient global brain ischemia. Neuroprotection was associated with a reduced HPA response to ischemia and was primarily decreased when corticosterone was injected at a dose that eliminated any difference in endogenous corticosterone levels between rats raised by mothers supplemented with corticosterone and their matched controls. These data suggest that an increased maternal care protects the offspring against ischemic neuronal damage and that at least a component of neuroprotection is mediated by a reduced response of the HPA axis to ischemia.
越来越多的证据强调了早期生活事件作为成年期健康预测指标的重要性。母体护理异常或其他形式的产后早期应激会引发行为的长期变化，并影响一生对疾病的易感性。其中一些变化可能是由下丘脑 - 垂体 - 肾上腺（HPA）轴的激活引起的，该轴总是与应激相关。我们使用了一种模型，即新生大鼠由饮用补充了0.2毫克/毫升皮质酮（啮齿动物中的主要糖皮质激素）的水的母鼠喂养。母鼠的血浆皮质酮水平升高到与轻度应激诱导的水平相似的程度。接受皮质酮治疗的母鼠的母性护理也有所增加。值得注意的是，由接受皮质酮治疗的母亲哺乳的成年大鼠可免受短暂性全脑缺血所致的神经元损伤和认知障碍。神经保护作用与HPA对缺血的反应降低有关，并且当以消除补充皮质酮的母亲饲养的大鼠与其匹配对照之间内源性皮质酮水平的任何差异的剂量注射皮质酮时，神经保护作用主要降低。这些数据表明，增加的母性护理可保护后代免受缺血性神经元损伤，并且至少部分神经保护作用是由HPA轴对缺血的反应降低介导的。
