Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, D-48149 Münster, Germany; Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, Germany.
J Psychiatr Res. 2013 Nov;47(11):1791-9. doi: 10.1016/j.jpsychires.2013.08.001. Epub 2013 Aug 22.
Genetic variants as well as increased serum levels of the neurotrophic factor S100B are associated with different psychiatric disorders. However, elevated S100B levels are also related to a better therapeutic outcome in psychiatric patients. The functional role of elevated S100B in psychiatric disorders is still unclear. Hence, this study was designed in order to elucidate the differential effects of S100B overexpression in interaction with chronic social stress during adolescence on emotional behavior and adult neurogenesis. S100B transgenic and wild-type mice were housed either in socially stable or unstable environments during adolescence, between postnatal days 28 and 77. In adulthood, anxiety-related behavior in the open field, dark-light, and novelty-induced suppression of feeding test as well as survival of proliferating hippocampal progenitor cells were assessed. S100B transgenic mice revealed significantly reduced anxiety-related behavior in the open field compared to wild-types when reared in stable social conditions. In contrast, when transgenic mice grew up in unstable social conditions, their level of anxiety-related behavior was comparable to the levels of wild-type mice. In addition, S100B overexpressing mice from unstable housing conditions displayed higher numbers of surviving newborn cells in the adult hippocampus which developed into mature neurons. In conclusion, elevated S100B levels increase the susceptibility to environmental stimuli during adolescence resulting in more variable behavioral and neural phenotypes in adulthood. In humans, this increased plasticity might lead to both, enhanced risk for psychiatric disorders in negative environments and improved therapeutic outcome in positive environments.
遗传变异以及神经营养因子 S100B 的血清水平升高与不同的精神障碍有关。然而，S100B 水平升高也与精神科患者的治疗效果更好有关。S100B 在精神障碍中的功能作用尚不清楚。因此，本研究旨在阐明 S100B 过表达与青春期慢性社会应激相互作用对情绪行为和成年神经发生的差异影响。S100B 转基因和野生型小鼠在青春期（出生后第 28 天至 77 天）期间分别在社会稳定或不稳定的环境中饲养。成年后，评估了开放场、明暗箱和新异诱发摄食抑制试验中的焦虑相关行为以及增殖海马祖细胞的存活情况。与在稳定的社会条件下饲养的野生型相比，在稳定的社会条件下饲养的 S100B 转基因小鼠在开放场中表现出明显减少的焦虑相关行为。相比之下，当转基因小鼠在不稳定的社会条件下长大时，它们的焦虑相关行为水平与野生型小鼠相当。此外，来自不稳定住房条件的 S100B 过表达小鼠在成年海马体中显示出更多存活的新生细胞，这些细胞发育成成熟神经元。总之，S100B 水平升高会增加青春期对环境刺激的敏感性，从而导致成年期行为和神经表型更加多变。在人类中，这种增加的可塑性可能导致在负面环境中增加患精神障碍的风险，以及在积极环境中改善治疗效果。
