ナカムラ　タカヒロ   NAKAMURA Takahiro   中村　孝博    所属   明治大学  農学部    職種   専任教授
発表年月日	2015/09/05
発表テーマ	Neural connections originating in the suprachiasmatic nucleus are necessary for estrous cyclicity
会議名	Asian Forum on Chronobiology in 2015
学会区分	研究会・シンポジウム等
発表形式	ポスター
単独共同区分	共同
開催地名	Sapporo, Japan
発表者・共同発表者	Shuto Mizuta, Kotomi Ohno, Wataru Nakamura, Takahiro J. Nakamura
概要	The central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus generates daily oscillations responsible for organizing the timing of most behaviors and physiological events in mammals, including the luteinizing hormone (LH) surge during the estrous cycle that triggers ovulation. In cycling female rodents, LH surge occurs on the day of proestrus at a specific critical period in the late afternoon, approximately 2-4 h before lights off. SCN lesioning abolishes this LH surge and prevents estrous cycles. Thus, timing-regulatory signals from the SCN are required for normal reproductive functions. It is known that these signals travel to specific sites in the brain and peripheral organs via neural connections and diffusible factors. However, which pathway is critical for reproductive functions, including the estrous cycle, remains unclear. In the present study, we employed a micro-knife originally designed by Prof. Halasz to sever nerves originating from the SCN. To determine the effect of the knife-cut on estrous cyclicity, we recorded wheel-running activity and examined vaginal smears of female C57BL/6J mice (n = 24) showing normal 4 or 5 days-estrous cycle before and after the knife-cut. Both assessments were continued for at least 15 days after the knife-cut, and then, the mice were killed with deep anesthesia, and their brains were removed and fixed with 4% paraformaldehyde. Coronal brain sections were obtained and stained with neutral red and anti-GFAP (Glial fibrillary acidic protein) antibody to determine the success of the knife-cut. In eight out of the 24 animals, the efferent connection from the SCN was completely cut, and seven out of these eight mice showed disappearance of the estrous cycle. In six mice, this neural connection was incompletely cut, and only one of them had a normal estrous cycle. Little or no cutting was achieved in the remaining 10 animals, and these mice showed a normal estrous cycle. In addition, mice experienced the knife-cut showed diurnal rhythms entrained with LD cycle and circadian rhythms in constant darkness, indicating that their SCN are intact. Our results strongly suggest that the timing-regulatory signaling via neural connections from the SCN is critical for estrous cyclicity.