PDF(Pubmed)
Abstract：
UNASSIGNED: The neurotransmitter serotonin is a key regulator of neurotransmission, mood, and behavior and is essential in neurodevelopment. Dysfunction in this important neurotransmitter system is connected to behavioral disorders such as depression and anxiety. We have previously shown that the developing serotonin system is sensitive to perinatal exposure to Western-style diet (WSD).
UNASSIGNED: To advance our hypothesis that perinatal WSD has a long-term impact on the serotonergic system, we designed a fluorescent immunohistochemistry experiment using antibodies against tryptophan hydroxylase 2 (TPH2) and vesicular glutamate transporter 3 (VGLUT3) to probe protein expression in the raphe subnuclei in 13-month-old Japanese macaques (Macaca fuscata; n = 22). VGLUT3 has been shown to be coexpressed in TPH2+ cells in the dorsal raphe (DR) and median raphe nucleus (MnR) of rodent raphe nuclei and may provide information about the projection site of serotonergic fibers into the forebrain. We also sought to improve scientific understanding of the heterogeneity of the serotonin production center for the central nervous system, the midbrain raphe nuclei.
UNASSIGNED: In this immunohistochemical study, we provide the most detailed characterization of the developing primate raphe to date. We utilize multi-level modeling (MLM) to simultaneously probe the contribution of WSD, offspring sex, and raphe anatomical location, to raphe neuronal measurements. Our molecular and morphological characterization revealed that the 13-month-old macaque DR is remarkably similar to that of adult macaques and humans. We demonstrate that vesicular glutamate transporter 3 (VGLUT3), which rodent studies have recently shown can distinguish raphe populations with distinct projection targets and behavioral functions, likewise contributes to the heterogeneity of the primate raphe.
UNASSIGNED: This study provides evidence that perinatal WSD has a long-term impact on the density of serotonin-producing neurons, potentially limiting serotonin availability throughout the brain. Due to the critical involvement of serotonin in development and behavior, these findings provide important insight into the mechanisms by which maternal nutrition and metabolic state influence offspring behavioral outcomes. Finally, these findings could inform future research focused on designing therapeutic interventions to optimize neural development and decrease a child\'s risk of developing a mental health disorder.
UNASSIGNED: To advance our hypothesis that perinatal WSD has a long-term impact on the serotonergic system, we designed a fluorescent immunohistochemistry experiment using antibodies against tryptophan hydroxylase 2 (TPH2) and vesicular glutamate transporter 3 (VGLUT3) to probe protein expression in the raphe subnuclei in 13-month-old Japanese macaques (Macaca fuscata; n = 22). VGLUT3 has been shown to be coexpressed in TPH2+ cells in the dorsal raphe (DR) and median raphe nucleus (MnR) of rodent raphe nuclei and may provide information about the projection site of serotonergic fibers into the forebrain. We also sought to improve scientific understanding of the heterogeneity of the serotonin production center for the central nervous system, the midbrain raphe nuclei.
UNASSIGNED: In this immunohistochemical study, we provide the most detailed characterization of the developing primate raphe to date. We utilize multi-level modeling (MLM) to simultaneously probe the contribution of WSD, offspring sex, and raphe anatomical location, to raphe neuronal measurements. Our molecular and morphological characterization revealed that the 13-month-old macaque DR is remarkably similar to that of adult macaques and humans. We demonstrate that vesicular glutamate transporter 3 (VGLUT3), which rodent studies have recently shown can distinguish raphe populations with distinct projection targets and behavioral functions, likewise contributes to the heterogeneity of the primate raphe.
UNASSIGNED: This study provides evidence that perinatal WSD has a long-term impact on the density of serotonin-producing neurons, potentially limiting serotonin availability throughout the brain. Due to the critical involvement of serotonin in development and behavior, these findings provide important insight into the mechanisms by which maternal nutrition and metabolic state influence offspring behavioral outcomes. Finally, these findings could inform future research focused on designing therapeutic interventions to optimize neural development and decrease a child\'s risk of developing a mental health disorder.
摘要：
未经证实：神经递质5-羟色胺是神经传递的关键调节因子，心情,和行为，在神经发育中至关重要。这个重要的神经递质系统的功能障碍与抑郁和焦虑等行为障碍有关。我们先前已经表明，发育中的5-羟色胺系统对围产期暴露于西式饮食（WSD）敏感。
UNASSIGNED：为了推进我们的假设，即围产期WSD对血清素能系统有长期影响，我们设计了一个荧光免疫组织化学实验，使用抗色氨酸羟化酶2（TPH2）和囊泡谷氨酸转运蛋白3（VGLUT3）的抗体来探测13个月大的日本猕猴（Macacafuscata；n=22）的中缝亚核中的蛋白表达。已显示VGLUT3在啮齿动物中缝核的背中缝（DR）和中缝核（MnR）的TPH2细胞中共表达，并可能提供有关血清素能纤维向前脑投射部位的信息。我们还试图提高对中枢神经系统5-羟色胺生产中心异质性的科学理解，中脑中缝核。
未经证实：在这项免疫组织化学研究中，我们提供了迄今为止发展中的灵长类动物raphe的最详细的表征。我们利用多层次建模(MLM)来同时探测WSD的贡献，后代性别，和raphe解剖位置，对神经元的测量。我们的分子和形态特征表明，13个月大的猕猴DR与成年猕猴和人类非常相似。我们证明囊泡谷氨酸转运体3（VGLUT3），最近的研究表明，啮齿动物可以区分具有不同投射目标和行为功能的raphe种群，同样有助于灵长类raphe的异质性。
UNASSIGNED：这项研究提供了证据，表明围产期WSD对产生5-羟色胺的神经元的密度有长期影响，可能限制血清素在整个大脑中的可用性。由于血清素在发育和行为中的关键参与，这些发现为母亲营养和代谢状态影响后代行为结果的机制提供了重要的见解。最后,这些发现可以为未来的研究提供信息，研究重点是设计治疗干预措施，以优化神经发育并降低儿童患精神健康障碍的风险。
UNASSIGNED：为了推进我们的假设，即围产期WSD对血清素能系统有长期影响，我们设计了一个荧光免疫组织化学实验，使用抗色氨酸羟化酶2（TPH2）和囊泡谷氨酸转运蛋白3（VGLUT3）的抗体来探测13个月大的日本猕猴（Macacafuscata；n=22）的中缝亚核中的蛋白表达。已显示VGLUT3在啮齿动物中缝核的背中缝（DR）和中缝核（MnR）的TPH2细胞中共表达，并可能提供有关血清素能纤维向前脑投射部位的信息。我们还试图提高对中枢神经系统5-羟色胺生产中心异质性的科学理解，中脑中缝核。
未经证实：在这项免疫组织化学研究中，我们提供了迄今为止发展中的灵长类动物raphe的最详细的表征。我们利用多层次建模(MLM)来同时探测WSD的贡献，后代性别，和raphe解剖位置，对神经元的测量。我们的分子和形态特征表明，13个月大的猕猴DR与成年猕猴和人类非常相似。我们证明囊泡谷氨酸转运体3（VGLUT3），最近的研究表明，啮齿动物可以区分具有不同投射目标和行为功能的raphe种群，同样有助于灵长类raphe的异质性。
UNASSIGNED：这项研究提供了证据，表明围产期WSD对产生5-羟色胺的神经元的密度有长期影响，可能限制血清素在整个大脑中的可用性。由于血清素在发育和行为中的关键参与，这些发现为母亲营养和代谢状态影响后代行为结果的机制提供了重要的见解。最后,这些发现可以为未来的研究提供信息，研究重点是设计治疗干预措施，以优化神经发育并降低儿童患精神健康障碍的风险。
