Hypothalamic circuit regulating colonic transit following chronic stress in rats

Yoshimoto S., Cerjak D., Babygirija R., Bulbul M., Ludwig K., Takahashi T.

STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, cilt.15, sa.2, ss.227-236, 2012 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 2
  • Basım Tarihi: 2012
  • Doi Numarası: 10.3109/10253890.2011.614297
  • Dergi Adı: STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.227-236
  • Anahtar Kelimeler: Acute stress, corticotropin-releasing hormone, chronic heterotypic stress, chronic homotypic stress, hypothalamus-pituitary-adrenal axis, oxytocin, CORTICOTROPIN-RELEASING-FACTOR, REPEATED RESTRAINT STRESS, WATER-AVOIDANCE STRESS, PARAVENTRICULAR NUCLEUS, OXYTOCIN ANTAGONIST, GASTRIC-MOTILITY, MAGNOCELLULAR NEURONS, FOS EXPRESSION, MOTOR RESPONSE, CENTRAL CRF
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Although acute stress accelerates colonic transit, the effect of chronic stress on colonic transit remains unclear. In this study, rats received repeated restraint stress (chronic homotypic stress) or various types of stress (chronic heterotypic stress) for 5 and 7 days, respectively. Vehicle saline, oxytocin (OXT), OXT receptor antagonist or corticotropin-releasing factor (CRF) receptor antagonists were administered by intracerebroventricular (ICV) injection prior to restraint stress for 90 min. Immediately after the stress exposure, the entire colon was removed and the geometric center (GC) of (NaCrO4)-Cr-51 (a nonabsorbable radioactive marker; 0.5 mu Ci) distribution was calculated to measure the transit. Gene expression of OXT and CRF in the paraventricular nucleus (PVN) was evaluated by in situ hybridization. Accelerated colonic transit with the acute stressor was no longer observed following chronic homotypic stress. This restored colonic transit was reversed by ICV injection of an OXT antagonist. In contrast, chronic heterotypic stress significantly accelerated colonic transit, which was attenuated by ICV injection of OXT and by a CRF receptor 1 antagonist. OXT mRNA expression in the PVN was significantly increased following chronic homotypic stress, but not chronic heterotypic stress. However, CRF mRNA expression in the PVN was significantly increased following acute and chronic heterotypic stress, but not chronic homotypic stress. These results indicate that central OXT and CRF play a pivotal role in mediating the colonic dysmotility following chronic stress in rats.

Although acute stress accelerates colonic transit, the effect of chronic stress on colonic transit remains unclear. In this study, rats received repeated restraint stress (chronic homotypic stress) or various types of stress (chronic heterotypic stress) for 5 and 7 days, respectively. Vehicle saline, oxytocin (OXT), OXT receptor antagonist or corticotropin-releasing factor (CRF) receptor antagonists were administered by intracerebroventricular (ICV) injection prior to restraint stress for 90 min. Immediately after the stress exposure, the entire colon was removed and the geometric center (GC) of Na 51CrO4 (a nonabsorbable radioactive marker; 0.5 mCi) distribution was calculated to measure the transit. Gene expression of OXT and CRF in the paraventricular nucleus (PVN) was evaluated by in situ hybridization. Accelerated colonic transit with the acute stressor was no longer observed following chronic homotypic stress. This restored colonic transit was reversed by ICV injection of an OXT antagonist. In contrast, chronic heterotypic stress significantly accelerated colonic transit, which was attenuated by ICV injection of OXT and by a CRF receptor 1 antagonist. OXT mRNA expression in the PVN was significantly increased following chronic homotypic stress, but not chronic heterotypic stress. However, CRF mRNA expression in the PVN was significantly increased following acute and chronic heterotypic stress, but not chronic homotypic stress. These results indicate that central OXT and CRF play a pivotal role in mediating the colonic dysmotility following chronic stress in rats.