| Title: | Loss of transient receptor potential channel 5 causes obesity and postpartum depression |
| Journal: | Cell |
| Published: | 2 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38959890/ |
| DOI: | https://doi.org/10.1016/j.cell.2024.06.001 |
| URL: | http://www.cell.com/article/S009286742400641X/pdf |
| Citations: | 2 (2 in last 2 years) as of 8 Aug 2024 |
Publication 11772
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Abstract
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.</p>
13 Keywords
- Animals
- Depression, Postpartum
- Female
- Humans
- Male
- Maternal Behavior
- Mice
- Mice, Inbred C57BL
- Neurons
- Obesity
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- TRPC Cation Channels
35 Authors
- Yongxiang Li
- Tessa M Cacciottolo
- Na Yin
- Yang He
- Hesong Liu
- Hailan Liu
- Yuxue Yang
- Elana Henning
- Julia M Keogh
- Katherine Lawler
- Edson Mendes de Oliveira
- Eugene J Gardner
- Katherine A Kentistou
- Panayiotis Laouris
- Rebecca Bounds
- Ken K Ong
- John R B Perry
- Inês Barroso
- Longlong Tu
- Jonathan C Bean
- Meng Yu
- Kristine M Conde
- Mengjie Wang
- Olivia Ginnard
- Xing Fang
- Lydia Tong
- Junying Han
- Tia Darwich
- Kevin W Williams
- Yongjie Yang
- Chunmei Wang
- Shelagh Joss
- Helen V Firth
- Yong Xu
- I Sadaf Farooqi
Enabling scientific discoveries that improve human health