Crosstalk of Urocortin and Inflammatory Cytokines in the Central Nervous System of Model Rats with Left Ventricular Heart Strain

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 142-166-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-153
Takanori Motoki*1, Miki Itohisa2, Eiichi Wake3, Takashi Urashima4, Ichiro Miyata5, Michihiro Yoshimura4, Katsuyoshi Tojo6 and Hiroyuki Ida4
1The Jikei Univ. School of Med, Katsushika Tokyo, Japan, 2The Jikei University School of Medicine, Tokyo, Tokyo, Japan, 3The Jikei Univ. School of Medicine, Tokyo, Japan, 4The Jikei University School of Medicine, Tokyo, Japan, 5Jikei Univ Schl of Med, Tokyo, Japan, 6Jikei Univ Sch of Med, Tokyo, Japan
Relation between neuropeptides and inflammatory cytokines in the central nervous system on the condition of heart failure remains unknown. In this study, we surgically created model rats with left ventricular heart strain by banding transverse aorta (Ao-banding), and four weeks later, sacrificed them after assessment of cardiac function by microcatheterization. Then, we divided their brains into nine sections and analyzed mRNA expressions of Urocortin-2, 3(Ucn-2, 3), CRF-R2a, TNF-a, IL-6, Suppressor of cytokine signaling-3 (SOCS-3) and protooncogene c-fos of those sections using real-time RT-PCR.
  In the Ao-banding group, Ucn-2 and Ucn-3 mRNA expressions were significantly elevated in striatum, hippocampus, thalamus, amygdala and cerebellum compared with control group. Unlike Ucn-2 mRNA expression, Ucn-3 mRNA expression was also elevated in hypothalamus. However, CRF-R2a mRNA expression was downregulated in frontal cortex, striatum, hippocampus, septum, thalamus and hypothalamus. In regard to expression level of TNFa mRNA, no significant difference between Ao-banding and control groups was recognized in any region of the brain. On the other hand, IL-6 mRNA expression of the Ao-banding group was markedly elevated in hippocampus, septum, hypothalamus, amygdala, and pituitary gland similar to patterns of Ucn-2 or Ucn-3 mRNA expression. Conversely, SOCS-3 mRNA expression of the Ao-banding group was markedly decreased in the almost same regions of the brain as IL-6. Protooncogene c-fos (third messenger of IL-6) mRNA level was upregulated in hippocampus, hypothalamus and cerebellum.

  Our data indicates that oxidative stress caused by left ventricular heart strain could probably induce chronic inflammation in the rat brain through Ucn-2, Ucn-3 and IL-6, suggesting the involvement of negative feedback of CRF receptors and cytokine signalings. Taken together, these results may lead to the elucidation of stress response mechanism in the central nervous system on the condition of heart failure.

Nothing to Disclose: TM, MI, EW, TU, IM, MY, KT, HI

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