Kaare Maria, Jayaram Mohan, Jagomäe Toomas, Singh Katyayani, Kilk Kalle, Mikheim Kaie, Leevik Marko, Leidmaa Este, Varul Jane, Nõmm Helis, Rähn Kristi, Visnapuu Tanel, Plaas Mario, Lilleväli Kersti, Schäfer Michael K E, Philips Mari-Anne, Vasar Eero
Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Centre of Excellence in Genomics and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Brain Sci. 2022 Dec 10;12(12):1696. doi: 10.3390/brainsci12121696.
In GWAS studies, the neural adhesion molecule encoding the neuronal growth regulator 1 () gene has been consistently linked with both depression and obesity. Although the linkage between and depression is the strongest, evidence also suggests the involvement of in a wide spectrum of psychiatric conditions. Here we show the expression of NEGR1 both in tyrosine- and tryptophan hydroxylase-positive cells. mice show a time-dependent increase in behavioral sensitization to amphetamine associated with increased dopamine release in both the dorsal and ventral striatum. Upregulation of transcripts encoding dopamine and serotonin transporters and higher levels of several monoamines and their metabolites was evident in distinct brain areas of mice. Chronic (23 days) escitalopram-induced reduction of serotonin and dopamine turnover is enhanced in mice, and escitalopram rescued reduced weight of hippocampi in mice. The current study is the first to show alterations in the brain monoaminergic systems in -deficient mice, suggesting that monoaminergic neural circuits contribute to both depressive and obesity-related phenotypes linked to the human gene.
在全基因组关联研究（GWAS）中，编码神经元生长调节因子1（NEGR1）的神经粘附分子一直与抑郁症和肥胖症相关联。尽管NEGR1与抑郁症之间的联系最为紧密，但有证据表明NEGR1也参与了多种精神疾病。在此我们展示了NEGR1在酪氨酸羟化酶和色氨酸羟化酶阳性细胞中的表达。NEGR1基因敲除小鼠对苯丙胺的行为敏化呈时间依赖性增加，同时背侧和腹侧纹状体中的多巴胺释放也增加。在NEGR1基因敲除小鼠的不同脑区，编码多巴胺和5-羟色胺转运体的转录本上调，几种单胺及其代谢产物水平升高。在NEGR1基因敲除小鼠中，慢性（23天）艾司西酞普兰诱导的5-羟色胺和多巴胺周转减少增强，并且艾司西酞普兰挽救了NEGR1基因敲除小鼠海马体重量的减轻。当前研究首次展示了NEGR1基因敲除小鼠脑单胺能系统的改变，提示单胺能神经回路与人类NEGR1基因相关的抑郁和肥胖相关表型均有关联。
