One of the most substantial and established environmental risk factors for neurological and psychiatric disorders is stress exposure, whose detrimental consequences hinge on several variables including time. In this regard the gestational period is known to present an intrinsic vulnerability to environmental insults and thus stressful events during pregnancy can lead to severe consequences on the offspring’s brain development with long-term repercussions throughout adulthood. On this basis, we investigated the long-lasting impact of prenatal stress exposure on the susceptibility to the experimental autoimmune encephalomyelitis (EAE), a well-established murine model of multiple sclerosis. Although stress is considered a triggering factor for this chronic, progressive, autoimmune disease, little is known about the underlying mechanisms. To this end, EAE was induced by immunization with MOG35-55/CFA and pertussis toxin administration in adult female C57BL/6 mice born from control or stressed dams exposed to restraint stress during the last days of gestation. Our results demonstrate that gestational stress induces a marked increase in the severity of EAE symptoms in adulthood. Further, we highlight an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE mice, as indicated by the higher levels of GPR17, a marker of immature oligodendrocyte precursor cells. These behavioral and molecular alterations are paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination. Since several already marketed drugs are able to modulate BDNF levels, these results pave the way to the possibility of repositioning these drugs in multiple sclerosis.

神经和精神疾病最重要和最确定的环境风险因素之一是压力暴露，其有害后果取决于包括时间在内的几个变量。在这方面，已知妊娠期呈现出对环境侮辱的内在脆弱性，因此妊娠期间的压力事件可能对后代的大脑发育造成严重后果，并在整个成年期产生长期影响。在此基础上，我们研究了产前压力暴露对实验性自身免疫性脑脊髓炎 (EAE) 易感性的长期影响，EAE 是一种成熟的多发性硬化小鼠模型。尽管压力被认为是这种慢性、进行性、自身免疫性疾病的触发因素，但对其潜在机制知之甚少。为此，EAE 是通过 MOG35-55/CFA 免疫和百日咳毒素给药诱导成年雌性 C57BL/6 小鼠出生的，这些小鼠是在妊娠最后几天暴露于约束压力的对照或应激母鼠。我们的研究结果表明，妊娠期压力会导致成年期 EAE 症状的严重程度显着增加。此外，我们强调了产前应激 EAE 小鼠脊髓中少突胶质细胞成熟的改变，如未成熟少突胶质前体细胞标志物 GPR17 的较高水平所示。这些行为和分子改变与神经营养因子 BDNF 的表达和信号变化平行，BDNF 是神经可塑性的重要介质，可能导致压力诱导的髓鞘再生受损。由于几种已经上市的药物能够调节 BDNF 水平，