Hefter Dimitri, Marti Hugo H, Gass Peter, Inta Dragos
RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Heidelberg, Germany.
RG Neuro- and Sensory Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
Front Psychiatry. 2018 Mar 29;9:106. doi: 10.3389/fpsyt.2018.00106. eCollection 2018.
Intrauterine or perinatal complications constitute a major risk for psychiatric diseases. Infants who suffered from hypoxia-ischemia (HI) are at twofold risk to develop schizophrenia in later life. Several animal models attempt to reproduce these complications to study the yet unknown steps between an insult in early life and outbreak of the disease decades later. However, it is very challenging to find the right type and severity of insult leading to a disease-like phenotype in the animal, but not causing necrosis and focal neurological deficits. By contrast, too mild, repetitive insults may even be protective conditioning effects. Thus, it is not surprising that animal models of hypoxia lead to mixed results. To achieve clinically translatable findings, better protocols are urgently needed. Therefore, we compare widely used models of hypoxia and HI and propose future directions for the field.
宫内或围产期并发症是精神疾病的主要风险因素。患有缺氧缺血(HI)的婴儿在日后患精神分裂症的风险会增加一倍。有几种动物模型试图重现这些并发症,以研究早年的损伤与数十年后疾病发作之间尚不为人知的过程。然而,要找到合适类型和严重程度的损伤,使其在动物身上导致类似疾病的表型,但又不引起坏死和局灶性神经功能缺损,是非常具有挑战性的。相比之下,过于轻微、重复性的损伤甚至可能具有保护作用——条件作用效应。因此,缺氧动物模型得出的结果参差不齐也就不足为奇了。为了获得具有临床可转化性的研究结果,迫切需要更好的实验方案。因此,我们比较了广泛使用的缺氧和HI模型,并为该领域提出了未来的发展方向。