Basic Medicine, Neuroscience


To Elucidate How Hypothalamic Endocrine Centers are Regulated by the Central Stress-Responsive Circuitries

Medical Sciences Course

  • Master / Doctoral Degree


ITOI, KeiichiITOI, Keiichi
ITOI, Keiichi

Professor, M.D. Ph.D.

*Concurrent Position

Research Theme

  • Identification of neurotransmitters and humoral factors which regulate CRF neurons
  • Elucidation of the physiological roles of the central noradrenergic systems in conveying stress responses
  • Development of mouse lines in which CRF neurons are visualized by fluorescent proteins
Research Keywords:

hypothalamus, glucocorticoids, catecholamines, mouse, gene

Technical Keywords:

genetically engineered mice, immunohistochemistry, immunofluorescence, patch-clamp, brain surgery

Laboratory Introduction

A living organism is equipped with basic biological systems for maintaining its life. These systems work for maintaining blood pressure, body temperature, electrolytes and metabolic balance, as well as for defense from stressors and sexual behaviors. The regulatory centers for the basic life maintenance reside in the hypothalamus and brainstem.
Experimental research works are carried out in Itoi Lab to elucidate the functional mechanisms of the hypothalamus and brainstem. By visualizing particular neurons in the brain, its morphological structures can be made clear, and in addition, functional characteristics of these neurons can be elucidated by analyzing their electrophysiological properties.
Recently, we developed a mouse model in which corticotropin-releasing factor (CRF) neurons are visualized by Venus (modified yellow fluorescent protein), so the electrical signals can be recorded directly from CRF neurons. Using these animal models, we are now studying the physiological implications of neural inputs and humoral factors that control hypothalamic CRF neurons.

Figure 1. Venus-labeled CRF neurons in the mouse hypothalamus

Figure 1. Venus-labeled CRF neurons in the mouse hypothalamus

Figure 2. Ablation of locus ceruleus noradrenergic neurons in mice

Figure 2. Ablation of locus ceruleus noradrenergic neurons in mice

Recent Publications

  • Itoi K, Talukder AF, Fuse T, Kaneko T, Ozawa R, Sato T, Sugaya T, Uchida K, Yamazaki M, Abe M, Natsume R, Sakimura K. Visualization of corticotropin-releasing factor neurons by fluorescent proteins in the mouse brain and characterization of labeled neurons in the paraventricular nucleus of the hypothalamus. Endocrinology 155:4054-4060, 2014
  • Itoi K, Ohara S, Kobayashi K. Selective ablation of dopamine b-hydroxylase neurons in the brain by immunotoxin-mediated neuronal targeting: new insights into brain catecholaminergic circuitry and catecholamine-related diseases. Advances in Pharmacology 68:155-166, 2013
  • Itoi K, Sugimoto N, Suzuki S, Sawada K, Das G, Uchida K, Fuse T, Ohara S, Kobayashi K. Targeting of locus ceruleus noradrenergic neurons expressing human interleukin-2 receptor a-subunit in transgenic mice by a recombinant immunotoxin anti-Tac(Fv)-PE38: a study for exploring noradrenergic influence upon anxiety-like and depression-like behaviors. J Neurosci 31:6132-6139, 2011
  • Uchida K, Kobayashi D, Das G, Onaka T, Inoue K, Itoi K. Participation of the prolactin-releasing peptide-containing neurons in the caudal medulla in conveying hemorrhagic stress-induced signals to the paraventricular nucleus of the hypothalamus. J Neuroendocrinol 22:33-42, 2010
  • Das G, Uchida K, Kageyama K, Iwasaki Y, Suda T, Itoi K. Glucocorticoid dependency of surgical stress-induced FosB/DFosB expression in the paraventricular and supraoptic nuclei of rat hypothalamus. J Neuroendocrinol 21:822-831, 2009