Scholarlink

<p>Understudied orphan GPCRs lack identified natural ligands, yet understanding their function is critical for therapeutic development. GPRC5B is a brain-enriched, retinoic acid (RA)-induced orphan GPCR. While RA is used to treat severe acne, chronic exposure is associated with depression, likely due to its inhibition of adult hippocampal neurogenesis. Here, we tested whether GPRC5B plays a role in the molecular and cellular mechanisms underlying RA-induced depressive-like behaviors in mice by suppressing adult hippocampal neurogenesis. We found that <i>Gprc5b</i> knockout (KO) mice were resilient to RA-induced behavioral effects and that RA increased GPRC5B expression in the hippocampal neurogenic subgranular zone. This correlated with RA-mediated inhibition of adult hippocampal neurogenesis, an effect absent in <i>Gprc5b</i> KO mice, which also exhibited a larger pool of proliferative neuronal stem cells. Collectively, these findings suggest that GPRC5B mediates RA-induced anti-neurogenic effects and depressive-like behaviors.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Orphan Receptor GPRC5B Controls Adult Hippocampal Neurogenesis and Affects Retinoic Acid-Mediated Behaviors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月7日

查看全文
  • Wenqi Fu,
  • Rana Alabdali,
  • Alireza Mousaei,
  • Fernanda Daher,
  • Nina Wettschureck,
  • David M. MacLean,
  • Manoela V. Fogaça,
  • Cesare Orlandi

摘要

Understudied orphan GPCRs lack identified natural ligands, yet understanding their function is critical for therapeutic development. GPRC5B is a brain-enriched, retinoic acid (RA)-induced orphan GPCR. While RA is used to treat severe acne, chronic exposure is associated with depression, likely due to its inhibition of adult hippocampal neurogenesis. Here, we tested whether GPRC5B plays a role in the molecular and cellular mechanisms underlying RA-induced depressive-like behaviors in mice by suppressing adult hippocampal neurogenesis. We found that Gprc5b knockout (KO) mice were resilient to RA-induced behavioral effects and that RA increased GPRC5B expression in the hippocampal neurogenic subgranular zone. This correlated with RA-mediated inhibition of adult hippocampal neurogenesis, an effect absent in Gprc5b KO mice, which also exhibited a larger pool of proliferative neuronal stem cells. Collectively, these findings suggest that GPRC5B mediates RA-induced anti-neurogenic effects and depressive-like behaviors.