Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Sci Rep. 2020 Jul 10;10(1):11411. doi: 10.1038/s41598-020-67692-1.
Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.
神经性厌食症是一种具有遗传、代谢和心理社会基础的复杂饮食失调症。使用全基因组方法，最近的研究将许多基因与该疾病联系起来。我们通过将这些基因投射到产前和成人人类大脑的参考转录组图谱中，以精细的细节来描述这些基因。我们发现，来自厌食症病例的诱导性干细胞研究的基因在外侧臂旁核中的表达水平更高。尽管较弱，但来自独立遗传研究的基因也发现了成年外侧臂旁核的表达富集。来自迄今为止最大的厌食症遗传研究的候选因果基因在下丘脑弓状核中的表达也得到了富集。我们还发现厌食症相关基因在成年和胎儿中缝核和腹侧被盖区的富集。受这些摄食回路富集的启发，我们测试了这些基因是否在小鼠下丘脑对禁食的反应，这突出了 Rps26 和 Dalrd3 的差异表达。这项工作通过提示皮质下食欲回路的紊乱，提高了我们对神经性厌食症神经生物学的理解。
