Department of Psychology and Institute for Neuroscience, University of Texas at Austin, 1 University Station A8000, Austin, TX 78712, USA.
Brain Res. 2011 Jan 7;1367:198-206. doi: 10.1016/j.brainres.2010.10.038. Epub 2010 Oct 19.
This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life.
这是第一项评估母婴分离对新生大鼠大脑区域性代谢能力影响的研究。母婴分离通常被认为对大鼠幼崽有压力。在新生期经历母婴分离后，霍尔茨曼青春期大鼠表现出类似抑郁的行为表型。然而，关于母婴分离对大鼠幼崽大脑的影响，信息还很缺乏。我们通过使用细胞色素氧化酶组织化学方法来研究这个问题，该方法反映了大脑代谢能力的长期变化，在两周的反复、长时间母婴分离后，我们将其与早期处理和未处理的幼崽进行了比较。定量图像分析显示，母婴分离降低了中前额皮质和伏隔核壳的细胞色素氧化酶活性。与雄性幼崽相比，母婴分离使雌性幼崽前额皮质中的细胞色素氧化酶活性降低的程度更大。早期处理降低了后顶叶皮层、腹侧被盖区和下托的细胞色素氧化酶活性，但增加了外侧额叶皮层的细胞色素氧化酶活性。早期处理对细胞色素氧化酶活性的性别依赖性影响仅限于中前额皮质。无论分离组如何，雌性幼崽的缰核和腹侧被盖区的细胞色素氧化酶活性都大于雄性幼崽。这些发现表明，生命早期的母婴分离导致新生大鼠大脑前额叶和中边缘区域的功能障碍，这可能导致生命后期的行为变化。
