一般口演（Oral）

Oral Neuroendcrine System 一般口演神経内分泌

7月26日（金）9:30～9:45　第7会場（朱鷺メッセ　2F　201B） 2O-07m2-1 BRAIN ACCESSIBILITY DELINEATES THE CENTRAL EFFECTS OF CIRCULATING GHRELIN Mario Perello（Perello Mario），Pablo De Francesco（De Francesco Pablo），Agustina Cabral（Cabral Agustina），Ｄａｎｉｅｌａ Lufrano（Lufrano Ｄａｎｉｅｌａ），Gimena Fernandez（Fernandez Gimena），Paula Cornejo（Cornejo Paula） Neurophysiology, Multidisciplinary Institute of Cell Biology, La Plata, Buenos Aires, Argentina Ghrelin is a hormone produced in the gastrointestinal tract that acts via the growth hormone secretagogue receptor. In the central nervous system, ghrelin signaling is able to recruit different neuronal targets that regulate behavioral, neuroendocrine, metabolic and autonomic effects of the hormone. Our laboratory investigates the effects of ghrelin in the brain using different pharmacologically and genetically modified mouse models. Notably, several studies using radioactive or fluorescent variants of ghrelin have found that the accessibility of circulating ghrelin into the mouse brain is strikingly low and restricted to some specific brain areas. A variety of studies addressing central effects of systemically injected ghrelin in mice have also provided indirect evidence that the accessibility of plasma ghrelin into the brain is limited. In the proposed talk I will review these previous observations done by our laboratory and by others, and discuss the putative pathways that would allow plasma ghrelin to gain access into the brain together with their physiological implications. In this context, I will describe the current knowledge about the molecular mechanisms and the neuronal circuits that mediate ghrelin actions. Finally, I will describe our recent findings on LEAP2 (Liver-expressed antimicrobial peptide 2), a recently described peptide that modulates the ghrelin receptor signaling. Overall, I will provide a very updated presentation describing the state of the arte of the ghrelin system.		7月26日（金）9:45～10:00　第7会場（朱鷺メッセ　2F　201B） 2O-07m2-2 単純糖質嗜好性はFGF21-オキシトシン系によるネガティブ・フィードバックにより制御される Tsutomu Sasaki（佐々木努），Sho Matsui（松居翔），Daisuke Kohno（河野大輔），Tadahiro Kitamura（北村忠弘）群馬大学生体調節研究所 We recently reported that neuronal SIRT1 suppresses simple sugar preference by enhancing FGF21 sensitivity of oxytocin (Oxt) neruons in mice (Nature Communications, 2018). Oxt neurons are mainly located in two places within the brain, the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus of the hypothalamus (SON). Therefore, we next asked which Oxt neurons are responsible for regulating simple sugar preference and the effect of SIRT1 on diet selection in mice. First, we checked the expression pattern of Klb in PVH and SON Oxt neurons by double staining of Klb in situ hybridization and anti-Oxt immunohistochemistry. We found more Klb-positive Oxt neuron in PVH than SON. Intraperitoneal injection of the recombinant murine FGF21 to mice induced c-Fos (a neuronal activation marker) in approximately 13 % of PVH Oxt, but no significant activation was detected in SON Oxt neurons. Therefore, PVH Oxt neurons are one of the target of FGF21 in the hypothalamus. We then confirmed the necessity of FGF21 signaling to Oxt neurons in regulating simple sugar preference by analyzing Oxt neuron-specific Klb knockout mice. These mice showed increased simple sugar preference, indicating that the action of FGF21 on Oxt neurons is required for suppressing the preference for simple sugar upon ingestion. We finally manipulated the SIRT1 expression levels in PVH vs. SON Oxt neurons by injecting Cre-inducible SIRT1 (WT or enzyme-dead H355Y mutant) AAV vector to Oxt-ires Cre mice. The overexpression of SIRT1-WT in PVH Oxt neurons significantly suppressed simple sugar preference, but no significant effect was observed in the SON-injected group. SIRT1-H355Y overexpression in PVH or SON did not affect simple sugar preference. Therefore, SIRT1 suppresses simple sugar preference through PVH Oxt neurons in mice. In summary, the simple sugar preference is regulated by the FGF21-oxytocin negative feedback system, and the PVH Oxt neurons are responsible for it. SIRT1 in the PVH Oxt neuron is sufficient to modulate the simple sugar preference, possibly by enhancing the expression of Klb and improving FGF21 sensitivity.

7月26日（金）10:00～10:15　第7会場（朱鷺メッセ　2F　201B） 2O-07m2-3 脳神経細胞内へのグルコース取り込みの増加によるATP量の維持と体液中グルコースの減少は、相乗的に老化のプロセスを遅らせる Mikiko Oka（岡未来子）¹，Emiko Suzuki（鈴木えみ子）^2,3，Koichi Iijima（飯島浩一）^4,5，Kanae Ando（安藤香奈絵）¹ ¹首都大院理学部生命科学 ²国立遺伝研 ³総研大院 ⁴国立長寿医療セ研究所アルツハイマー ⁵名古屋市大薬 Aging is controlled by metabolic interplay between the central nervous system and peripheral tissues. For example, reducing circulating glucose and stored energy in peripheral tissue via calorie restriction (CR) delays aging in various species. On the other hand, glucose metabolism reduces during aging in the brain, which correlates with age-associated decline in neuronal functions. These reports suggest that metabolic changes in the brain and peripheral tissues may play different roles in animal aging. Here we report that enhancement of glucose uptake to maintain ATP levels in the brain neurons and CR to reduce circulating glucose levels synergistically antagonize the aging in Drosophila. By using transgenic flies expressing genetically encoded fluorescent ATP biosensor, we found that the ATP levels reduced in the soma of the brain neurons during aging. Enhancement of glucose uptake by neuronal overexpression of a glucose transporter was sufficient to suppress age-dependent declines in the ATP levels and locomotor functions. Interestingly, CR treatment also suppressed the age-dependent reduction in ATP levels in brain neurons, suggesting that maintaining ATP levels in aged brains may be a common pathway to counteract organismal aging. Finally, we demonstrated that increasing glucose uptake in brain neurons and CR synergistically extended the life span. Our results suggest that increasing glucose levels in the brain neurons and reducing circulating glucose levels synergistically antagonize the aging processes via maintaining of neuronal ATP levels. Elucidation of the interplay between brain neurons and peripheral tissues in glucose metabolism may shed light on the mechanisms underlying aging.		7月26日（金）10:15～10:30　第7会場（朱鷺メッセ　2F　201B） 2O-07m2-4 分娩様式の違いが神経系の機能に異なる影響を及ぼす Keiko Ikeda（池田啓子）^1,2，Hiroshi Onimaru（鬼丸洋）³，Kiyoshi Kawakami（川上潔）² ¹国際医療福祉大学医学部生理学 ²自治医大細胞生物研究部 ³昭和大学医学部生理学 The prevalence of delivery through cesarean-section (C-section) has been increasing worldwide. It is well known that different modes of delivery, such as vaginal birth and C-section, are associated with different behavior and incidence of some diseases in humans. However, little is known about how delivery stimuli affect short- and long-term brain function. We previously reported that Atp1a2 homozygous knockout (Atp1a2^-/-) neonates showed different phenotypes depending on the mode of delivery; Atp1a2^-/- mice born by vaginal delivery started spontaneous breathing, while Atp1a2^-/- mice born by C-section showed a complete absence of breathing followed by their death. This life or death phenotype prompted us to examine several aspects of the neonatal brain following C-section or vaginal delivery. However, further analyses of the Atp1a2^-/- mice were hindered by their immediate death after birth. Therefore, we examined the acute effect of delivery with a focus on neural function by comparing several aspects of wild-type neonatal brains following vaginal delivery or C-section. We found different levels of several monoamines in the whole brains of mouse neonates born by C-section delivery and vaginal delivery. We also detected different levels of transporters and channel proteins and a different pattern of c-Fos expression in the brain. Furthermore, we observed differences in various behavioral analyses when the mice became adults. These results suggest that vaginal delivery affects brain function as well as the respiratory neural network both acutely and in the long term. We emphasize that the mode of delivery may affect neural network formation at birth and long-term neural function via changes in the levels of different neurotransmitters and different membrane proteins.