Central Institute of Mental Health Mannheim (ZI), University of Heidelberg, Germany.
Neuroscience. 2012 Sep 18;220:267-76. doi: 10.1016/j.neuroscience.2012.06.016. Epub 2012 Jun 16.
Experimental evidence in mice indicates that environmental conditions affect females and males differently. However, in a recent study analyzing the heterozygous mutation of brain-derived neurotrophic factor (BDNF), both sexes presented a similar emotional phenotype, which became obvious only under impoverished, but not in enriched conditions suggesting an "enrichment-induced" rescue. To investigate the basis of this behavioral "rescue" effect, we analyzed neurochemical changes (BDNF expression, serotonergic changes, and corticosterone) in the hippocampus, frontal cortex and hypothalamus of animals housed under respective conditions. In male mice, enrichment induced an increase of BDNF expression in the hippocampus of both BDNF heterozygous (BDNF(+/-)) and wild-types. Notably, in enriched-reared BDNF(+/-) mice BDNF mRNA and protein increased to levels comparable to those of wild-types in impoverished environment. In the frontal cortex of males, only wild-types presented an enrichment-induced increase of BDNF mRNA, while no effect of environment could be detected in BDNF protein levels of the male hypothalamus. A further male-specific effect of "environment" is the significant reduction of hypothalamic 5-hydroxyindoleacetic acid in enriched-housed wild-types. In female mice, environmental enrichment did not affect BDNF expression in the hippocampus and hypothalamus. However, comparable to males, an enrichment-induced increase of BDNF mRNA was detected in the frontal cortex of wild-types only. In contrast to males, no influence of environment on serotonergic parameters was observed. Male and female corticosterone levels were neither affected by "genotype" nor by "environment". In conclusion, we propose that the rescue of the emotional phenotype by environmental enrichment in BDNF(+/-) mice is directed by distinct mechanisms in males and females. Only in male BDNF(+/-) mice the rescue is related to an increase in hippocampal BDNF expression suggesting that enrichment triggers different neuronal systems in a gender-specific manner.
实验证据表明，环境条件对雌性和雄性的影响不同。然而，在最近一项分析脑源性神经营养因子（BDNF）杂合突变的研究中，雌雄两性均表现出相似的情绪表型，这种表型仅在贫困环境中明显，而在丰富环境中则不明显，这表明存在一种“丰富诱导”的拯救作用。为了探究这种行为“拯救”效应的基础，我们分析了在不同环境下饲养的动物的神经化学变化（BDNF 表达、5-羟色胺能变化和皮质酮），包括海马体、前额皮质和下丘脑。在雄性小鼠中，丰富环境诱导 BDNF 杂合子（BDNF(+/-)）和野生型小鼠的海马体中 BDNF 表达增加。值得注意的是，在丰富环境中饲养的 BDNF(+/-) 小鼠中，BDNF mRNA 和蛋白质水平增加到与贫困环境中野生型相当的水平。在雄性小鼠的前额皮质中，只有野生型小鼠的 BDNF mRNA 表达增加，而环境对雄性下丘脑的 BDNF 蛋白水平没有影响。“环境”对雄性的另一个特定影响是丰富环境显著降低了雄性下丘脑的 5-羟色胺酸。在雌性小鼠中，环境丰富对海马体和下丘脑的 BDNF 表达没有影响。然而，与雄性小鼠类似，仅在野生型小鼠的前额皮质中检测到 BDNF mRNA 的诱导增加。与雄性小鼠不同的是，环境对 5-羟色胺能参数没有影响。雌雄小鼠的皮质酮水平既不受“基因型”也不受“环境”的影响。总之，我们提出，在 BDNF(+/-) 小鼠中，环境丰富对情绪表型的拯救作用是由雌雄两性不同的机制介导的。只有雄性 BDNF(+/-) 小鼠的拯救作用与海马体 BDNF 表达的增加有关，这表明丰富环境以性别特异性的方式触发了不同的神经元系统。
