New genetic approaches to investigate integrative defence mechanisms based on hypothalamo-neurohypophysial system

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04027
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: UETA YOICHI 産業医科大学, 医学部, 教授 (10232745)
• Co-Investigator(Kenkyū-buntansha): 吉村 充弘 産業医科大学, 医学部, 講師 (00464462) ; 丸山 崇 産業医科大学, 医学部, 准教授 (20533194)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 遺伝子改変動物 / 下垂体後葉ホルモン / バゾプレッシン / オキシトシン / 体液バランス / 疼痛 / 性周期 / ストレス

Outline of Final Research Achievements

Novel transgenic rats expressing the fusion genes of the arginine vasopressin (AVP)-eGFP, oxytocin (OXT)-mRFP1 and AVP-/OXT-hM3Dq-mCherry were generated by the genetic techniques. In AVP-/OXT-hM3Dq-mCherry transgenic rats, AVP/OXT neurons showed mCherry and expressed Fos protein after peripherally administered clozapine-N oxide (CNO). AVP/OXT neurons in the hypothalamic paraventricular nucleus project their axon terminals to the posterior pituitary, external layer of the median eminence, and spinal cord. We examined the effects of body fluid imbalance, nociceptive stimuli, estrus cycle and ovariectomy with/without replacement of estrogen on AVP/OXT system. We also demonstrated that selective activation of AVP/OXT neurons after peripherally administered CNO caused significant increases of plasma AVP/OXT levels and changed behaviors such as feeding and drinking. These studies revealed that central AVP/OXT systems are involved in various physiological responses to stressful conditions.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

遺伝子改変技術を用いて作出したトランスジェニックラットを用いて、神経内分泌系および自律神経系の統合中枢・司令塔である視床下部室傍核に局在する神経分泌ニューロンの細胞体で産生された下垂体後葉ホルモンが下垂体後葉系、正中隆起を介した下垂体前葉系、および脊髄下行系を介して多彩な生理機能を発揮することを明らかにすることができた。下垂体後葉系を基軸とした体液の恒常性破綻、加齢、慢性疼痛、閉経に関わる生体防御反応の統合とその破綻機構を明らかにすることは超高齢社会を迎えた我が国にとって社会的な意義がある。