Oxytocin released from mouse hypothalamus and nerve endings by extracellular applicaion of beta-NAD+ and cyclic ADP-ribose

Jin, Duo; Liu, Hongxiang; Lopatina, O. V.; Hashii, Minako; Yokoyama, Shigeru; Koizumi, Keita; Amina, Sarwat; Shuto, Satoshi; Shiraishi, Yoshitake; Tanaka, Shigenori; Higashida, Haruhiro

doi:10.1038/nprot.2007.214

Cited by 2 publications

(2 citation statements)

References 5 publications

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“…A recent study suggested that NR supplementation did not change CD38 expression 35 . However, in vitro studies have shown that NAD + applied to the mouse hypothalamus leads to OT release 36 . It is reasonable to assume that an elevation in NAD + levels by NR in the hypothalamus is responsible for repair of the OT release.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder

Gerasimenko

Cherepanov

Furuhara

et al. 2020

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oxytocin (ot) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. in addition, ot acts as an anxiolytic factor and is released during stress. Based on the activity of CD38 as an enzyme that produces the calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), CD157, a sister protein of CD38, has been considered a candidate mediator for the production and release of OT and its social engagement and anti-anxiety functions. However, the limited expression of CD157 in the adult mouse brain undermined confidence that CD157 is an authentic and/or actionable molecular participant in OT-dependent social behaviour. Here, we show that CD157 knockout mice have low levels of circulating OT in cerebrospinal fluid, which can be corrected by the oral administration of nicotinamide riboside, a recently discovered vitamin precursor of nicotinamide adenine dinucleotide (NAD). NAD is the substrate for the CD157-and CD38-dependent production of cADPR. Nicotinamide riboside corrects social deficits and fearful and anxiety-like behaviours in CD157 knockout males. These results suggest that elevating NAD levels with nicotinamide riboside may allow animals with cADPR-and OT-forming deficits to overcome these deficits and function more normally. Oxytocin (OT) plays a role in social recognition, behaviour, and memory through a positive feedback system involving OT-induced OT release in the brain 1-3. OT is released in response to emotional, physical, and pharmacological stresses 1,2. It is known that OT counteracts stress-induced anxiety. Accordingly, OT in the brain is considered an anxiolytic factor 2,3. CD38 and CD157 are two related cell-surface molecules that form the calcium-mobilizing second messenger, cyclic ADP-ribose (cADPR) from nicotinamide adenine dinucleotide (NAD) 4-8 , the central coenzyme of metabolism 9. cADPR functions as a potential intracellular second messenger that triggers Ca 2+ mobilization from ryanodine receptor Ca 2+ pools to produce cellular responses 4,6. In the hypothalamus, cADPR triggers an increase in intracellular free Ca 2+ concentrations and, subsequently, Ca 2+-dependent OT release from oxytocinergic neurons 10. When this signalling cascade was blocked in CD38 knockout (CD38KO) mice, social memory and recognition and parental nurturing behaviours were disrupted, mainly due to reduced OT secretion 11,12. The treated mice increased levels of social behaviour, which was invoked by local re-expression of human CD38 in the

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Section: Discussionmentioning

confidence: 99%

Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder

Gerasimenko

Cherepanov

Furuhara

et al. 2020

Sci Rep

Self Cite

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show abstract

“…Amount of OT released during 5 min from isolated nerve endings on the coated glass was determined by replacing incubation Lock solution with or without the known concentration of OT (for stimulation). Therefore, we used the following formula to calculate the ratio of OT release under various conditions of preand post-stimulation: OT release ratio = (OT concentration incubated with OT) -(OT concentration without OT)/ (pre-stimulation of OT level=100 pM), according to the method described previously (Jin et al, 2007b).…”

Section: Ot Release From Nerve Endingsmentioning

confidence: 99%

Oxytocin-induced elevation of ADP-ribosyl cyclase activity, cyclic ADP-riboseor Ca2+ concentrations is involved in autoregulation of oxytocin secretionin the hypothalamus and posterior pituitary in male mice

et al. 2010

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Oxytocin released from mouse hypothalamus and nerve endings by extracellular applicaion of beta-NAD+ and cyclic ADP-ribose

Cited by 2 publications

References 5 publications

Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder

Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder

Oxytocin-induced elevation of ADP-ribosyl cyclase activity, cyclic ADP-riboseor Ca2+ concentrations is involved in autoregulation of oxytocin secretionin the hypothalamus and posterior pituitary in male mice

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