当前位置: X-MOL 学术Cereb. Cortex › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Diminished Myoinositol in Ventromedial Prefrontal Cortex Modulates the Endophenotype of Impulsivity.
Cerebral Cortex ( IF 3.7 ) Pub Date : 2020-05-14 , DOI: 10.1093/cercor/bhz317
Bianca Jupp 1 , Steve J Sawiak 2 , Bastiaan van der Veen 1 , Suzanne Lemstra 1 , Chiara Toschi 1 , Rebecca L Barlow 3 , Anton Pekcec 3 , Tom Bretschneider 3 , Janet R Nicholson 3 , Trevor W Robbins 1 , Jeffrey W Dalley 1, 4
Affiliation  

Maladaptive impulsivity manifests in a variety of disorders, including attention-deficit hyperactivity disorder (ADHD), depression, and substance use disorder. However, the etiological mechanisms of impulsivity remain poorly understood. In the present study, we used in-vivo proton magnetic resonance spectroscopy (1H-MRS) to investigate neurometabolite content in the prefrontal cortex (PFC) and striatum of rats exhibiting low- versus high-impulsive (LI, HI) behavior on a visual attentional task. We validated our 1H-MRS findings using regionally resolved ex-vivo mass spectroscopy, transcriptomics, and site-directed RNA interference in the ventromedial PFC. We report a significant reduction in myoinositol levels in the PFC but not the striatum of HI rats compared with LI rats. Reduced myoinositol content was localized to the infralimbic (IL) cortex, where significant reductions in transcript levels of key proteins involved in the synthesis and recycling of myoinositol (IMPase1) were also present. Knockdown of IMPase1in the IL cortex increased impulsivity in nonimpulsive rats when the demand on inhibitory response control was increased. We conclude that diminished myoinositol levels in ventromedial PFC causally mediate a specific form of impulsivity linked to vulnerability for stimulant addiction in rodents. Myoinositol and related signaling substrates may thus offer novel opportunities for treating neuropsychiatric disorders comorbid with impulsive symptomology.

中文翻译:

腹内侧前额叶皮层肌醇减少调节冲动的内表型。

适应不良的冲动表现为多种疾病,包括注意力缺陷多动障碍 (ADHD)、抑郁症和物质使用障碍。然而,冲动的病因机制仍然知之甚少。在本研究中,我们使用体内质子磁共振波谱 (1H-MRS) 来研究在视觉上表现出低与高冲动 (LI、HI) 行为的大鼠前额叶皮层 (PFC) 和纹状体中的神经代谢物含量注意任务。我们在腹内侧 PFC 中使用区域解析的离体质谱、转录组学和定点 RNA 干扰验证了我们的 1H-MRS 发现。我们报告了与 LI 大鼠相比,HI 大鼠的 PFC 肌醇水平显着降低,但纹状体没有。减少的肌醇含量位于边缘下 (IL) 皮层,其中还存在参与肌醇 (IMPase1) 合成和回收的关键蛋白质的转录水平显着降低。当对抑制反应控制的需求增加时,IL 皮质中 IMPase1 的敲低增加了非冲动大鼠的冲动性。我们得出结论,腹内侧 PFC 中肌醇水平的降低介导了一种特定形式的冲动,这种冲动与啮齿类动物兴奋剂成瘾的脆弱性有关。因此,肌醇和相关信号底物可能为治疗与冲动症状并存的神经精神疾病提供新的机会。当对抑制反应控制的需求增加时,IL 皮质中 IMPase1 的敲低增加了非冲动大鼠的冲动性。我们得出结论,腹内侧 PFC 中肌醇水平的降低介导了一种特定形式的冲动,这种冲动与啮齿类动物兴奋剂成瘾的脆弱性有关。因此,肌醇和相关信号底物可能为治疗与冲动症状并存的神经精神疾病提供新的机会。当对抑制反应控制的需求增加时,IL 皮质中 IMPase1 的敲低增加了非冲动大鼠的冲动性。我们得出结论,腹内侧 PFC 中肌醇水平的降低介导了一种特定形式的冲动,这种冲动与啮齿类动物兴奋剂成瘾的脆弱性有关。因此,肌醇和相关信号底物可能为治疗与冲动症状并存的神经精神疾病提供新的机会。
更新日期:2020-01-02
down
wechat
bug