UNDERSTANDING NEURODEVELOPMENT IN MACAQUES WITH DIFFERENT REARING EXPERIENCES

了解不同饲养经历的猕猴的神经发育

• 批准号: 8172398
• 负责人: MAR M SANCHEZ
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172398
• 关键词: Adolescence; Adolescent; Affect; Age; Amygdaloid structure; Animals; Brain; Brain region; Caring; Computer Retrieval of Information on Scientific Projects Database; Development; Diffusion Magnetic Resonance Imaging; Employee Strikes; Funding; Grant; Gray unit of radiation dose; Hippocampus (Brain); Hydrocortisone; Infant; Institution; Life; Life Stress; Long-Term Effects; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Modeling; Parietal; Period Analysis; Prefrontal Cortex; Research; Research Personnel; Resources; Source; Stress; Structure; Technology; United States National Institutes of Health; Visual Cortex; brain volume; experience; in vivo; infancy; interest; myelination; neurodevelopment; neuroimaging; nonhuman primate; white matter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We used a naturalistic nonhuman primate model of early life stress (ELS) consisting of poor maternal care to characterize the long-term impact on neurodevelopment using in vivo neuroimaging technology, using structural MRI, diffusion tensor imaging (DTI) and MR spectroscopy. In order to understand the effects on brain development, we had to examine normative brain development during the rhesus monkey infant period, and analyzed potential associations with socioemotional maturation. Our findings revealed dramatic brain developmental changes during infancy, particularly fast and striking between 2 weeks and 3 months, including increased brain volume, deepening of sulci and intense rates of myelination. We found that at 2 weeks some cortical regions, such as the prefrontal cortex, were not yet myelinated. These findings underscored the high vulnerability of the brain, particularly prefrontal circuits with protracted development, to stress experienced at these early ages, which could result in alterations in normal brain developmental trajectories. We demonstrated that ELS indeed affects brain development using a model of poor maternal care. For example, long-term alterations in brain myelinated tracts were detected during adolescence, particularly in prefrontal, temporal, parietal and visual cortices. We found a significant decrease in amygdala volume of animals with ELS, despite no differences in overall brain, gray or white matter volumes, or in other regions of interest (e.g. hippocampus). Interestingly, the amygdala volume negatively correlated with basal cortisol at month 1, when animals experienced the highest levels of stress as infants. Altogether, our findings suggest the ELS has long-term effects on the structure and connectivity of limbic brain regions of nonhuman primates. The reduced amygdala volume detected during the adolescent period seems related to the stress-induced elevations in cortisol early in life.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们使用了一个自然主义的非人灵长类动物模型的早期生活压力（ELS），包括产妇护理不佳的特点，在体内神经成像技术，使用结构MRI，扩散张量成像（DTI）和磁共振波谱的神经发育的长期影响。 为了了解对大脑发育的影响，我们必须检查恒河猴婴儿时期的正常大脑发育，并分析与社会情感成熟的潜在关联。我们的研究结果揭示了婴儿期大脑发育的巨大变化，特别是在2周到3个月之间，包括脑体积增加，脑沟加深和髓鞘形成的强烈速度。我们发现，在2周时，一些皮质区域，如前额叶皮质，还没有髓鞘。这些发现强调了大脑的高度脆弱性，特别是具有长期发展的前额叶回路，在这些早期年龄经历的压力，这可能导致正常大脑发育轨迹的改变。 我们证明，ELS确实会影响大脑发育，使用一个模型的母亲照顾不好。例如，在青春期检测到大脑有髓鞘束的长期变化，特别是在前额叶，颞叶，顶叶和视觉皮质。我们发现ELS动物的杏仁核体积显著减少，尽管整个大脑、灰质或白色物质体积或其他感兴趣区域（例如海马体）没有差异。有趣的是，杏仁核的体积与基础皮质醇在1个月时呈负相关，当动物经历了最高水平的压力作为婴儿。 总而言之，我们的研究结果表明ELS对非人类灵长类动物边缘脑区域的结构和连接性具有长期影响。在青少年时期检测到的杏仁核体积减少似乎与生命早期应激诱导的皮质醇升高有关。