Group of Neurosteroids and Behavior, Institut de Neurociències, Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, Edifici B, Cerdanyola del Vallès 08193, Barcelona, Spain.
Group of Neuroplasticity and Regeneration, Institut de Neurociències, Departament de Biologia Cel·lular, de Fisiologia i de Immunologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Prog Neurobiol. 2014 Feb;113:95-105. doi: 10.1016/j.pneurobio.2013.07.007. Epub 2013 Aug 17.
Several works have pointed out the importance of the neurosteroid allopregnanolone for the maturation of the central nervous system and for adult behavior. The alteration of neonatal allopregnanolone levels in the first weeks of life alters emotional adult behavior and sensory gating processes. Without ruling out brain structures, some of these behavioral alterations seem to be related to a different functioning of the hippocampus in adult age. We focus here on the different behavioral studies that have revealed the importance of neonatal allopregnanolone levels for the adult response to novel environmental stimuli, anxiety-related behaviors and processing of sensory inputs (prepulse inhibition). An increase in neonatal physiological allopregnanolone levels decreases anxiety and increases novelty responses in adult age, thus affecting the individual response to environmental cues. These effects are also accompanied by a decrease in prepulse inhibition, indicating alterations in sensory gating that have been related to that present in disorders, such as schizophrenia. Moreover, behavioral studies have shown that some of these effects are related to a different functioning of the dorsal hippocampus, as the behavioral effects (decrease in anxiety and locomotion or increase in prepulse inhibition) of intrahippocampal allopregnanolone infusions in adult age are not present in those subjects in whom neonatal allopregnanolone levels were altered. Recent data indicated that this hippocampal involvement may be related to alterations in the expression of gamma-aminobutyric-acid receptors containing α4 and δ subunits, molecular alterations that can persist into adult age and that can, in part, explain the reported behavioral disturbances.
已有多项研究指出神经甾体孕烷醇酮对中枢神经系统成熟和成年行为的重要性。生命最初几周内新生孕烷醇酮水平的改变会改变成年后的情绪行为和感觉门控过程。尽管尚未排除大脑结构的影响，但其中一些行为改变似乎与成年后海马体的不同功能有关。我们在此重点介绍了一些不同的行为研究，这些研究揭示了新生孕烷醇酮水平对成年后对新环境刺激、焦虑相关行为和感觉输入处理（前脉冲抑制）的反应的重要性。新生生理孕烷醇酮水平的增加会降低成年后的焦虑感并增加对新奇事物的反应，从而影响个体对环境线索的反应。这些影响还伴随着前脉冲抑制的降低，表明感觉门控发生改变，这与精神分裂症等疾病中存在的改变有关。此外，行为研究表明，其中一些影响与背侧海马体的不同功能有关，因为在成年时向海马内注射孕烷醇酮会产生降低焦虑和运动或增加前脉冲抑制的行为效应，但在新生孕烷醇酮水平改变的动物中不存在这些效应。最近的数据表明，这种海马体的参与可能与含有α4 和 δ 亚基的γ-氨基丁酸受体表达的改变有关，这些分子改变可以持续到成年期，并在一定程度上解释了所报道的行为障碍。
