Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Nuevo León, San Nicolas de los Garza, México.
Unidad de Neurometabolismo, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, San Nicolas de los Garza, México.
J Neurochem. 2021 Feb;156(4):415-434. doi: 10.1111/jnc.15141. Epub 2020 Sep 9.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disease which involves functional and structural defects in selective central nervous system (CNS) regions that harm function and individual ability to process and respond to external stimuli. Individuals with ASD spend less time engaging in social interaction compared to non-affected subjects. Studies employing structural and functional magnetic resonance imaging reported morphological and functional abnormalities in the connectivity of the mesocorticolimbic reward pathway between the nucleus accumbens and the ventral tegmental area (VTA) in response to social stimuli, as well as diminished medial prefrontal cortex in response to visual cues, whereas stronger reward system responses for the non-social realm (e.g., video games) than social rewards (e.g., approval), associated with caudate nucleus responsiveness in ASD children. Defects in the mesocorticolimbic reward pathway have been modulated in transgenic murine models using D2 dopamine receptor heterozygous (D2+/-) or dopamine transporter knockout mice, which exhibit sociability deficits and repetitive behaviors observed in ASD phenotypes. Notably, the mesocorticolimbic reward pathway is modulated by systemic and central inflammation, such as primed microglia, which occurs during obesity or maternal overnutrition. Therefore, we propose that a positive energy balance during obesity/maternal overnutrition coordinates a systemic and central inflammatory crosstalk that modulates the dopaminergic neurotransmission in selective brain areas of the mesocorticolimbic reward pathway. Here, we will describe how obesity/maternal overnutrition may prime microglia, causing abnormalities in dopamine neurotransmission of the mesocorticolimbic reward pathway, postulating a possible immune role in the development of ASD.
自闭症谱系障碍（ASD）是一种复杂的神经发育疾病，涉及选择性中枢神经系统（CNS）区域的功能和结构缺陷，这些缺陷损害了功能和个体对外界刺激的处理和反应能力。与未受影响的受试者相比，ASD 患者在社交互动上花费的时间更少。研究采用结构和功能磁共振成像技术，报告了中边缘奖赏通路的连接在对社会刺激的反应中存在形态和功能异常，在对视觉线索的反应中存在内侧前额叶皮层功能减退，而对非社会领域（例如视频游戏）的奖赏系统反应比社会奖赏（例如认可）更强，这与 ASD 儿童的尾状核反应有关。使用多巴胺 D2 受体杂合子（D2+/-）或多巴胺转运体敲除小鼠的转基因鼠模型已经调节了中边缘奖赏通路的缺陷，这些模型表现出 ASD 表型中的社交缺陷和重复行为。值得注意的是，中边缘奖赏通路受到全身和中枢炎症的调节，例如被激活的小胶质细胞，这种情况发生在肥胖或母体营养过剩期间。因此，我们提出，肥胖/母体营养过剩期间的正能平衡协调了全身和中枢炎症的串扰，调节了中边缘奖赏通路中选择性脑区的多巴胺能神经传递。在这里，我们将描述肥胖/母体营养过剩如何激活小胶质细胞，导致中边缘奖赏通路的多巴胺能神经传递异常，并假设在 ASD 的发展中存在免疫作用。
