Departament de Psicobiologia i Metodologia en Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Valles, Campus de Bellaterra, Barcelona, Spain.
Psychoneuroendocrinology. 2013 Aug;38(8):1397-406. doi: 10.1016/j.psyneuen.2012.12.007. Epub 2013 Jan 5.
Diverse studies indicate that the alteration of the physiological levels of neurosteroids in early neonatal phases provokes alterations in the maturation of certain cerebral structures. Allopregnanolone (ALLO) has important modulatory effects in the hippocampus during the postnatal period where the adult pattern of inhibitory transmission is being established. In order to study whether endogenous neonatal ALLO levels would be a determinant parameter involved in mediating adult hippocampal GABAA system maturation, we investigated the effects of neonatal finasteride (50mg/kg, SC) treatment and ALLO (ALLO; 20mg/kg, SC) supplementation on an animal behavioural model with relevance to neurodevelopmental disorder, such as schizophrenia. Two sets of experiments were conducted. Neonatal treatment (from postnatal day (pnd) 5 to pnd9) was performed in 23 male Wistar rats and steroid quantification was performed in hippocampal homogenates at pnd9. A second group (n=127) underwent neonatal treatment (pnd5-pnd9) and were submitted to hippocampal surgery at 80d. The behavioural response to bilateral intrahippocampal neurosteroid administration (ALLO, 0.2μg/0.5μl per side or pregnenolone sulphate 5ng/0.5μl per side) on novelty-induced exploration activity and prepulse inhibition (PPI) was assessed at 95d. Results showed that neonatal ALLO and finasteride administration decreased novelty directed exploratory behaviour and impaired the prepulse inhibition of the acoustic startle response at 95 days of age. Moreover, intrahippocampal ALLO increased head-dipping behaviour independently of the neonatal treatment, while intrahippocampal ALLO decreased PPI only in finasteride and ALLO groups. The results obtained in the present study indicate the importance of neonatal neurosteroid levels in the development of hippocampal function and their relevance in a behavioural phenotype that some have likened to that present in schizophrenia.
多项研究表明，早期新生儿阶段神经甾体的生理水平改变会引起某些大脑结构的成熟改变。在出生后期间，变孕烷醇酮（ALLO）对海马具有重要的调节作用，在该期间正在建立成年抑制性传递模式。为了研究内源性新生 ALLO 水平是否会成为参与调节成年海马 GABA A 系统成熟的决定因素，我们研究了新生期非那雄胺（50mg/kg，SC）处理和 ALLO（ALLO；20mg/kg，SC）补充对具有神经发育障碍相关性的动物行为模型的影响，例如精神分裂症。进行了两组实验。在 23 只雄性 Wistar 大鼠中进行了新生期治疗（从出生后第 5 天到第 9 天），并在第 9 天进行了海马匀浆中的类固醇定量。第二组（n=127）接受了新生期治疗（第 5-9 天），并在 80d 时进行了海马手术。在 95d 时，评估了双侧海马内神经甾体给药（ALLO，每侧 0.2μg/0.5μl 或孕烯醇酮硫酸盐 5ng/0.5μl）对新奇诱导的探索活动和预脉冲抑制（PPI）的行为反应。结果表明，新生期 ALLO 和非那雄胺给药降低了对新奇事物的探索行为，并损害了 95 天龄时的听觉起始反应的预脉冲抑制。此外，海马内 ALLO 增加了头浸行为，而与新生期治疗无关，而海马内 ALLO 仅降低了仅在非那雄胺和 ALLO 组中的 PPI。本研究的结果表明，新生神经甾体水平在海马功能发育中的重要性及其在某些人认为类似于精神分裂症的行为表型中的相关性。
