Developmental changing in GABAergic synapse formation and intracellular Cl- concentration related with respiratory ryhthm during prenatal mouse medulla.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Seinan Jo Gakuin University (2017-2018); University of the Ryukyus (2016)
• Principal Investigator: Okabe Akihito 西南女学院大学, 保健福祉学部, 教授 (10313941)
• Co-Investigator(Kenkyū-buntansha): 清水 千草 琉球大学, 医学(系)研究科(研究院), 准教授 (70435072)
• Research Collaborator: Takayama Chitoshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: GABA / VGAT / KCC2 / 舌下神経核 / 呼吸リズム / 胎生期

Outline of Final Research Achievements

Role of GABAergic transmission in regulation of medullary respiration-related rhythmic activity (RRA) perinatally is yet to be determined. We previously reported that mean numbers of RRA recorded from mouse hypoglossal nucleus (12N) were significantly increased from embryonic day (E) 16 to postnatal day (P) 0. Here, we examined how GABA and chloride co-transporters contribute to RRA during development in 12N. We performed immunohistochemistry for KCC2 and VGAT in 12N of wild type mouse. Both of them were already expressed on E16 and gradually increased by P0. We also recorded intracellular Cl- concentration ([Cl-]i) in motoneurons of mouse hypoglossal nucleus using gramicidin perforate patch clamp method. The mean value [Cl-]i of prenatal 12N motoneurons was higher than that of postnatal 12N motoneurons. These results suggest that decreasing [Cl-]i levels caused by increasing KCC2 levels in 12N could play important roles in regulating the frequency of RRA during development.

Free Research Field

呼吸生理学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られる結果は、GABA入力と舌下神経核運動神経細胞との間に生じる、正常呼吸リズム獲得過程のメカニズムを明らかにすることである。このことは、乳幼児突然死症候群や、出産時における呼吸不全のリスクを予測し、治療法開発の一助となる。
また、本研究に代表される生体のリズム形成過程の解明は、脊髄におけるロコモーションなどの運動リズムの発生機序に適用でき、脊髄損傷などの治療に応用できると考えている。