| Regulation of stress susceptibility by chromatin-binding protein PHF6 in the pituitary intermediate lobe |
| 論文作者 |
Liu, B; Wang, JJ; Wu, XH; Gan, LH; Sun, JJ; Wang, GZ; Li, Q; Huang, J |
| 期刊/會議名稱 |
MOLECULAR PSYCHIATRY |
| 論文年度 |
2025 |
| 論文類別 |
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| 摘要 |
The pituitary intermediate lobe (IL) is a surprisingly understudied pituitary region. Here, we find that chromatin-binding protein PHF6 is enriched in the pituitary IL and plays a crucial role in regulating stress susceptibility in mice. Conditional knockout of Phf6 in PHF6-positive IL cells (ILPHF6 cells) significantly reduces acute stress-induced anxiety-like behaviors and chronic stress-induced depression-like behaviors by impairing cellular activation and the release of stress-related hormones. Mechanistically, conditional knockout of Phf6 in the pituitary IL cells downregulates the calcium channel beta 3 subunit and suppresses transcription of stress-responsive genes. Chemogenetic inhibition of ILPHF6 cells reduces stress susceptibility, whereas activation of these cells increases anxiety-like behaviors. Circuit tracing demonstrates that ILPHF6 cells receive direct synaptic inputs from CRH-expressing neurons in the hypothalamus paraventricular nucleus (PVN), positioning ILPHF6 cells as a crucial interface between neural stress signals and endocrine output. These findings reveal a previously unknown mechanism in the regulation of stress susceptibility that operates through anxiogenic ILPHF6 cells, providing a perspective for understanding how stress susceptibility is molecularly tuned. |
| 影響因子 |
10.1 |
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