慢性便秘症に新たな突破口～排便をつかさどる脳中枢の仕組みを世界で初めて解明～

2025-10-10 九州大学

(図1) バリントン核に対する光遺伝学を用いた便秘治療への試み

<関連情報>

• https://www.kyushu-u.ac.jp/ja/researches/view/1340
• https://www.kyushu-u.ac.jp/f/63506/25_1010_03.pdf
• https://www.cmghjournal.org/article/S2352-345X(25)00176-6/fulltext

バリントン核:速やかな排便反応と遅延した排便反応を示す橋排便脳領域 Barrington’s Nucleus: A Pontine Defecation Brain Area Exhibiting Prompt and Delayed Defecation Responses

Kota Bussaka ∙ Yoshimasa Tanaka ∙ Kunio Kondoh ∙ … ∙ Eikichi Ihara ∙ Yasuhiko Minokoshi ∙ Yoshihiro Ogawa
Cellular and Molecular Gastroenterology and Hepatology  Published:October 10, 2025
DOI:https://doi.org/10.1016/j.jcmgh.2025.101635

Abstract

Background & Aims

Chronic constipation has attracted considerable attention because of its negative impact on quality of life. Although defecation depends on local anorectal motility coordinated by the central nervous system, how it is regulated by the brain remains unclear.

Methods

Brain areas responsible for defecation, known as the defecation brain area (DBA), were identified using a trans-synaptic tracing virus, pseudorabies virus (PRV). Candidate DBAs were assessed using opto- and chemogenetic methods and in vivo monitoring of neural activity.

Results

A significant number of PRV-infected cells were observed in the Barrington’s nucleus (Bar), locus coeruleus (LC), ventrolateral periaqueductal gray (vlPAG), and paraventricular hypothalamic nucleus (PVH) following virus infection in the distal colon. Opto- and chemogenetic activation studies revealed that vesicular glutamate transporter 2 (VGluT2) neurons in the Bar and LC, and corticotropin-releasing hormone (CRH) neurons in the Bar exhibit prompt (short-acting) and delayed (long-lasting) contractions in the distal colon, respectively. Their neural activities increased and peaked during spontaneous defecation. In contrast, activation of tyrosine hydroxylase neurons in the LC, which co-express VGluT2, exhibited no response. PRV experiments revealed that PVH^VGluT2 and vlPAG^CRH neurons are upstream neurons that connect to Bar^VGluT2 neurons, and their optogenetic activation resulted in a contraction of the distal colon.

Conclusions

The study is the first to show that the Bar works as the pontine DBA, where Bar^VGluT2 and Bar^CRH neurons exert prompt and delayed defecation activity, respectively. PVH^VGluT2 and vlPAG^CRH neurons are candidates for upstream neurons that regulate defecation through Bar^VGluT2 neurons.