Columba-Cabezas Sandra, Iaffaldano Grazia, Chiarotti Flavia, Alleva Enrico, Cirulli Francesca
Section of Inflammatory and Demyelinating Diseases of the Nervous System, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
J Neuroimmunol. 2009 Jul 25;212(1-2):10-6. doi: 10.1016/j.jneuroim.2009.05.007. Epub 2009 Jun 2.
Brief maternal separations of neonatal animals can exert long-lasting effects on the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether manipulations of the mother-infant interaction could affect susceptibility to immune-mediated diseases, such experimental autoimmune encephalomyelitis (EAE), and whether this effect would be mediated by changes in leptin which has been shown to regulate disease susceptibility and severity at adulthood. Given the different gender susceptibility to EAE previously described, we tested also whether early experiences could differentially affect the two genders. To this purpose, female and male C56BL/6 mice were subjected to handling (15 min daily) postnatally, from day 2 until day 14. All subjects were weaned at 21 days. At 7 weeks of age mice were immunized with MOG(35-55) to actively induce EAE. We thus determined the effect of neonatal handling on plasma concentrations of testosterone in male mice and leptin in both genders at different times post EAE induction. Our results show that early experiences influence susceptibility to EAE in a gender-specific manner, early manipulations resulting in an enhancement of sex-related differences in susceptibility. These effects were associated with changes in the testosterone profile of male subjects. Changes in leptin levels during the preclinical stage of EAE may predict a more severe disease course.
新生动物与母亲的短暂分离会对神经内分泌系统的反应性产生持久影响。本研究的目的是调查母婴互动的改变是否会影响对免疫介导疾病（如实验性自身免疫性脑脊髓炎，EAE）的易感性，以及这种影响是否会由瘦素的变化介导，瘦素已被证明在成年期可调节疾病易感性和严重程度。鉴于先前描述的EAE的不同性别易感性，我们还测试了早期经历是否会对两种性别产生不同影响。为此，对雌性和雄性C57BL/6小鼠在出生后第2天至第14天每天进行15分钟的抚摸处理。所有小鼠在21天断奶。7周龄时，用MOG(35-55)对小鼠进行免疫以主动诱导EAE。我们由此确定了新生期抚摸处理对EAE诱导后不同时间雄性小鼠血浆睾酮浓度和两性瘦素浓度的影响。我们的结果表明，早期经历以性别特异性方式影响对EAE的易感性，早期处理导致易感性方面性别相关差异增大。这些影响与雄性受试者睾酮水平的变化有关。EAE临床前期瘦素水平的变化可能预示着疾病进程更严重。
