Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy.
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, I-00161 Rome, Italy.
Eur Neuropsychopharmacol. 2014 Jun;24(6):986-95. doi: 10.1016/j.euroneuro.2013.12.010. Epub 2013 Dec 30.
Psychiatric diseases may often represent the consequence of exposure to adverse events early in life. Accordingly, exposure to stress during gestation in rats has a strong impact on development and can cause long-term abnormalities in adult behavior. Considering that neuronal plasticity has emerged as a major vulnerability element in psychiatric disorders, we investigated the postnatal developmental profile of Brain-Derived Neurotrophic Factor expression (BDNF), an important mediator for long-term functional deterioration associated to mental illness, in male and female rats following exposure to prenatal stress (PNS). Since we found that the majority of alterations became fully manifest at early adulthood, we tried to prevent these abnormalities with an early pharmacological intervention. To address this point, we treated rats during adolescence with the multi-receptor antipsychotic lurasidone, which was proven to be effective in animal models of schizophrenia. Interestingly, we show that lurasidone treatment was able to prevent the reduction of BDNF expression in adult rats that were exposed to PNS. Collectively, our results provide further support to the notion that exposure to early life stress has a negative impact on neuronal plasticity and that pharmacological intervention during critical time windows may prove effective in preventing neuroplastic dysfunction, leading to long-term beneficial effects on brain function.
精神疾病可能经常代表生命早期暴露于不利事件的后果。因此，大鼠妊娠期暴露于应激会对发育产生强烈影响，并可能导致成年后行为长期异常。鉴于神经元可塑性已成为精神疾病中一个主要的脆弱性因素，我们研究了产前应激（PNS）暴露后雄性和雌性大鼠脑源性神经营养因子表达（BDNF）的产后发育情况，BDNF 是与精神疾病相关的长期功能恶化的重要介质。由于我们发现大多数改变在成年早期完全显现，因此我们试图通过早期药物干预来预防这些异常。为了解决这一问题，我们在青春期用多受体抗精神病药鲁拉西酮治疗大鼠，该药物已被证明在精神分裂症动物模型中有效。有趣的是，我们发现鲁拉西酮治疗能够预防 PNS 暴露的成年大鼠中 BDNF 表达的减少。总的来说，我们的结果进一步支持了这样一种观点，即生命早期应激暴露对神经元可塑性有负面影响，而在关键时间窗口进行药物干预可能有助于预防神经可塑性功能障碍，从而对大脑功能产生长期的有益影响。
