2024年7月2日，来自英国剑桥大学I. Sadaf Farooqi等研究人员合作在《细胞》杂志发表了标题为“Loss of transient receptor potential channel 5 causes obesity and postpartum depression.”的研究成果，发现瞬时受体电位通道5的缺失会导致肥胖和产后抑郁。
据介绍，下丘脑神经回路调节本能行为，如寻找食物、战斗/逃跑反应、社交和母性照料。
研究人员发现染色体Xq23上的微缺失干扰了大脑表达的瞬态受体电位（TRP）通道5（TRPC5）。该通道家族能检测感觉刺激，并将其转化为大脑可解读的电信号。雄性TRPC5缺失携带者表现出寻食、肥胖、焦虑和自闭症，这些症状在携带人类TRPC5功能缺失突变的基因敲入雄性小鼠身上得到了重现。携带TRPC5基因缺失的雌性产后抑郁严重。
作为母亲，雌性的基因敲除小鼠表现出失张力和类似抑郁症的行为，对后代的照顾能力受损。在下丘脑室旁核的催产素神经元中缺失Trpc5会导致雌雄小鼠肥胖和产后抑郁行为，而在基因敲入小鼠的催产素神经元中过表达Trpc5则会逆转这些表型。研究人员证明了TRPC5在介导人类先天性生存行为（包括寻食和母性照料）中发挥着关键作用。
研究揭示了小鼠和人类中TRPC5的基因的破坏会导致肥胖、觉醒程度提高、焦虑、强烈的食物寻找和食物囤积以及导致母亲产后抑郁行为，进一步阐述了表达TRPC5的神经元回路在介导对生存至关重要的稳态和适应性行为反应中发挥着重要作用。
Highlights
- In humans, deletion of TRPC5 causes obesity, anxiety, autism, and postpartum depression
- Male and female mice harboring a human TRPC5 mutation recapitulate these phenotypes
- Effects are mediated by TRPC5 acting on hypothalamic Pomc and oxytocin neurons
- Brain-expressed TRPC5 regulates instinctive behaviors essential for survival
Summary
Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care.
文章来源：
Yongxiang Li, Tessa M. Cacciottolo et al, Loss of transient receptor potential channel 5 causes obesity and postpartum depression.DOI: 10.1016/j.cell.2024.06.001, Cell：最新IF：66.85
