Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice

金沢大学医薬保健研究域医学系Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt -/-, Cd38 -/-) or its receptor (Oxtr -/-) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt -/- and Cd38 -/-, but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.3082047

Dual Nature of RAGE in Host Reaction and Nurturing the Mother–Infant Bond

Non-enzymatic glycation is an unavoidable reaction that occurs across biological taxa. The final products of this irreversible reaction are called advanced glycation end-products (AGEs). The endogenously formed AGEs are known to be bioactive and detrimental to human health. Additionally, exogenous food-derived AGEs are debated to contribute to the development of aging and various diseases. Receptor for AGEs (RAGE) is widely known to elicit biological reactions. The binding of RAGE to other ligands (e.g., high mobility group box 1, S100 proteins, lipopolysaccharides, and amyloid-β) can result in pathological processes via the activation of intracellular RAGE signaling pathways, including inflammation, diabetes, aging, cancer growth, and metastasis. RAGE is now recognized as a pattern-recognition receptor. All mammals have RAGE homologs; however, other vertebrates, such as birds, amphibians, fish, and reptiles, do not have RAGE at the genomic level. This evidence from an evolutionary perspective allows us to understand why mammals require RAGE. In this review, we provide an overview of the scientific knowledge about the role of RAGE in physiological and pathological processes. In particular, we focus on (1) RAGE biology, (2) the role of RAGE in physiological and pathophysiological processes, (3) RAGE isoforms, including full-length membrane-bound RAGE (mRAGE), and the soluble forms of RAGE (sRAGE), which comprise endogenous secretory RAGE (esRAGE) and an ectodomain-shed form of RAGE, and (4) oxytocin transporters in the brain and intestine, which are important for maternal bonding and social behaviors

Distinct physical condition and social behavior phenotypes of CD157 and CD38 knockout mice during aging.

The ability of CD38 and CD157 to utilize nicotinamide adenine dinucleotide (NAD) has received much attention because the aging-induced elevation of CD38 expression plays a role in the senescence-related decline in NAD levels. Therefore, it is of interest to examine and compare the effects of age-associated changes on the general health and brain function impairment of Cd157 and Cd38 knockout (CD157 KO and CD38 KO) mice. The body weight and behaviors were measured in 8-week-old (young adult) or 12-month-old (middle-aged) male mice of both KO strains. The locomotor activity, anxiety-like behavior, and social behavior of the mice were measured in the open field and three-chamber tests. The middle-aged CD157 KO male mice gained more body weight than young adult KO mice, while little or no body weight gain was observed in the middle-aged CD38 KO mice. Middle-aged CD157 KO mice displayed increased anxiety-like behavior and decreased sociability and interaction compared with young adult KO mice. Middle-aged CD38 KO mice showed less anxiety and hyperactivity than CD157 KO mice, similar to young adult CD38 KO mice. The results reveal marked age-dependent changes in male CD157 KO mice but not in male CD38 KO mice. We discuss the distinct differences in aging effects from the perspective of inhibition of NAD metabolism in CD157 and CD38 KO mice, which may contribute to differential behavioral changes during aging

山羊の採食行動に及ぼす暖地型イネ科牧草草種(ダリスグラス及びバミューダグラス)の影響

A study was conducted on the relation between ingestive behaviour of grazing goats and tropical grasses. Three goats fitted with oesophageal fistulae were used for measuring dry matter intake per bite (DMI/TB) from Dallis grass (Paspalum dilatatum) and Bermuda grass (Cynodon dactylon) pastures at 59 and 80 days of regrowth. Whole plants, harvested parts of plants by goats, un harvested parts of the plants from each pasture were collected for chemical analyses and determination of in vitro dry matter digestibility (IVDMD) and energy. Digestible dry matter intake per bite (DDMI/TB) and digestible energy intake per bite (DEI/TB) were estimated. The results obtained were as follows: Harvested parts by goats showed higher crude protein, IVDMD and digestible energy, however lower cell wall constituents than those of unharvested parts at two growth stages in both species. Goats had larger DMI/TB at 80 days of regrowth comparing with 59 days, however DDMI/TB and DEI/TB showed little differences between two stages in both grasses. There was no differences between grasses in DMI/TB, DDMI/TB and DEI/TB at both stages.暖地型イネ科牧草草種(ダリスグラス及びバミューダグラス)と山羊の採食行動との関連について,食道フィステル装着山羊3頭を供試し,採食部と残食部の化学成分,in vitro乾物消化率及び可消化エネルギー並びにひと噛み当たりの乾物摂取量,可消化乾物摂取量及び可消化エネルギー摂取量を指標として検討した.得られた結果は次のとおりである.供試ダリスグラス及びバミューダグラスの採食部の粗蛋白質含量, in vitro乾物消化率及び可消化エネルギーは残食部のそれらと比べ高い値を示し,採食部の細胞壁構成成分含量は残食部のそれと比べ概して低い値を示した.また,ダリスグラス及びバミューダグラス草地における山羊のひと噛み当たりの乾物摂取量は再生59日目よりも80日目で高い値を示したが,いずれの時期においても両草種間でほとんど差は認められなかった.さらに,ひと噛み当たりの可消化乾物摂取量及び可消化エネルギー摂取量は両生育段階及び草種間で大きな差は認められなかった