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Potential role of primed microglia during obesity on the mesocorticolimbic circuit in autism spectrum disorder
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-08-09 , DOI: 10.1111/jnc.15141
Luis A- Trujillo Villarreal 1, 2 , Marcela Cárdenas-Tueme 3 , Roger Maldonado-Ruiz 1, 2 , Diana Reséndez-Pérez 3 , Alberto Camacho-Morales 1, 2
Affiliation  

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.

中文翻译:

肥胖期间引发小胶质细胞在自闭症谱系障碍中皮层皮质回路中的潜在作用

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,损害功能和个体处理和响应外部刺激的能力。与未受影响的受试者相比,患有自闭症的人花费在社交互动上的时间更少。使用结构和功能磁共振成像的研究报告了伏伏核与腹侧被盖区(VTA)之间的中皮层皮质奖励路径的连通性在形态和功能方面的异常,以响应社会刺激,以及对视觉的响应减弱了内侧前额叶皮层提示,而非社会领域(例如,视频游戏)的奖励系统响应要比社会奖励(例如,批准)更强,与ASD儿童的尾状核反应有关。使用D2多巴胺受体杂合子(D2 +/-)或多巴胺转运蛋白敲除小鼠已在转基因鼠模型中调节了中皮层皮质奖励途径的缺陷,这些小鼠表现出社交能力缺陷和在ASD表型中观察到的重复行为。值得注意的是,中皮层皮质的奖励途径是由全身性和中枢性炎症调节的,例如引发的小胶质细胞,它发生于肥胖或母亲营养过剩的时期。因此,我们建议肥胖/母亲营养过剩期间的正能量平衡可以协调全身性和中枢性炎症串扰,该串扰调节中皮质糖皮质激素奖励途径的选择性大脑区域中的多巴胺能神经传递。在这里,我们将描述肥胖/母亲过度营养如何引发小胶质细胞,
更新日期:2020-08-09
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