Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats

Vas, Szilvia; Ádori, Csaba; Könczöl, Katalin; Kátai, Zita; Pap, Dorottya; Papp, Rege Sugárka; Bagdy, György; Palkovits, Miklós; Tóth, Zsuzsanna

doi:10.1371/journal.pone.0059809

Cited by 54 publications

(34 citation statements)

References 54 publications

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“…Data on REM sleep alterations upon nesfatin-1 i.c.v. injection are unequivocal as both a reduction (Vas et al 2013) as well as a slight increase (Jego et al 2012) have been published; in line with the latter observation, blockade of endogenous nesfatin-1 expression negatively affects REM sleep (Jego et al 2012).…”

Section: Sleepsupporting

confidence: 65%

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Nesfatin-1: functions and physiology of a novel regulatory peptide

Dore

Levata

Lehnert

et al. 2017

Journal of Endocrinology

117

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Nesfatin-1 was identified in 2006 as a potent anorexigenic peptide involved in the regulation of homeostatic feeding. It is processed from the precursor-peptide NEFA/ nucleobindin 2 (NUCB2), which is expressed both in the central nervous system as well as in the periphery, from where it can access the brain via non-saturable transmembrane diffusion. In hypothalamus and brainstem, nesfatin-1 recruits the oxytocin, the melancortin and other systems to relay its anorexigenic properties. NUCB2/nesfatin-1 peptide expression in reward-related areas suggests that nesfatin-1 might also be involved in hedonic feeding. Besides its initially discovered anorexigenic properties, over the last years, other important functions of nesfatin-1 have been discovered, many of them related to energy homeostasis, e.g. energy expenditure and glucose homeostasis. Nesfatin-1 is not only affecting these physiological processes but also the alterations of the metabolic state (e.g. fat mass, glycemic state) have an impact on the synthesis and release of NUCB2 and/or nesfatin-1. Furthermore, nesfatin-1 exerts pleiotropic actions at the level of cardiovascular and digestive systems, as well as plays a role in stress response, behavior, sleep and reproduction. Despite the recent advances in nesfatin-1 research, a putative receptor has not been identified and furthermore potentially distinct functions of nesfatin-1 and its precursor NUCB2 have not been dissected yet. To tackle these open questions will be the major objectives of future research to broaden our knowledge on NUCB2/nesfatin-1.

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Section: Sleepsupporting

confidence: 65%

“…REM sleep rebound in turn activates NUCB2/nesfatin-1 neurons (Vas et al 2013). Data on REM sleep alterations upon nesfatin-1 i.c.v.…”

Section: Sleepmentioning

confidence: 99%

Nesfatin-1: functions and physiology of a novel regulatory peptide

Dore

Levata

Lehnert

et al. 2017

Journal of Endocrinology

117

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“…Food intake and body weight were monitored during the entire experiment. The vigilance states were classified using conventional criteria as described earlier (72,73). The following parameters were calculated: time spent in wake, REM, SWS1 and SWS2 (per hour), sleep fragmentation, sleep-onset REM, number of transitions (NREM-wake and NREM-REM), and number of REM episodes.…”

Section: Methodsmentioning

confidence: 99%

Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns

Bergman

Ádori

Vas

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Narcolepsy is a chronic sleep disorder, likely with an autoimmune component. During 2009 and 2010, a link between A(H1N1)pdm09 Pandemrix vaccination and onset of narcolepsy was suggested in Scandinavia. In this study, we searched for autoantibodies related to narcolepsy using a neuroanatomical array: rat brain sections were processed for immunohistochemistry/double labeling using patient sera/cerebrospinal fluid as primary antibodies. Sera from 89 narcoleptic patients, 52 patients with other sleep-related disorders (OSRDs), and 137 healthy controls were examined. Three distinct patterns of immunoreactivity were of particular interest: pattern A, hypothalamic melanin-concentrating hormone and proopiomelanocortin but not hypocretin/orexin neurons; pattern B, GABAergic cortical interneurons; and pattern C, mainly globus pallidus neurons. Altogether, 24 of 89 (27%) narcoleptics exhibited pattern A or B or C. None of the patterns were exclusive for narcolepsy but were also detected in the OSRD group at significantly lower numbers. Also, some healthy controls exhibited these patterns. The antigen of pattern A autoantibodies was identified as the common C-terminal epitope of neuropeptide glutamic acidisoleucine/α-melanocyte-stimulating hormone (NEI/αMSH) peptides. Passive transfer experiments on rat showed significant effects of pattern A human IgGs on rapid eye movement and slow-wave sleep time parameters in the inactive phase and EEG θ-power in the active phase. We suggest that NEI/αMSH autoantibodies may interfere with the fine regulation of sleep, contributing to the complex pathogenesis of narcolepsy and OSRDs. Also, patterns B and C are potentially interesting, because recent data suggest a relevance of those brain regions/neuron populations in the regulation of sleep/arousal.arcolepsy is a chronic neurological disease characterized by irresistible daytime sleepiness (hypersomnia) and disturbed nocturnal sleep. Narcolepsy can be divided into two types: narcolepsy with cataplexy (NC) and narcolepsy without cataplexy. A typical feature of NC is sudden loss of muscle tone triggered by emotions (cataplexy). Other symptoms of narcolepsy are, for example, hypnagogic or hypnopompic hallucinations and sleep paralyses (1). The age of onset is usually around 12-16 y of age, but the disease is often diagnosed several years later (1). It affects ∼25-50 per 100,000 individuals, and the yearly incidence rate has been estimated to be around 1 per 100,000 person-y (2). Narcolepsy has a major negative impact on the quality of life, afflicting both physical and mental parameters (3). A major hallmark of narcolepsy (mostly NC) is the loss of hypocretin-1/ orexin-A (Hcrt/Orx), a neuropeptide hormone initially discovered independently by two groups (4, 5), by either a destruction of the orexinergic neurons or a selective down-regulation of Hcrt/Orx expression (6, 7). Consequently, a typical feature of NC is low levels (<110 pg/mL) of Hcrt/Orx peptide in the cerebrospinal fluid (CSF) (1).The causes of the loss of Hcrt/Orx and narcolep...

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“…This peptide influences water intake (64), energy expenditure (56), sleep (54), blood pressure (61,63), and reproduction (18,19). Serum nesfatin-1 levels correlated positively with increasing BMI, demonstrating that systemic nesfatin-1 levels may be influenced by the body fat (1,44).…”

Section: Artykuł Przeglądowy Reviewmentioning

confidence: 99%

Role of nesfatin-1 in the metabolism of skeletal tissues

Puzio¹,

Tymicki²,

Predka³

et al. 2018

Medycyna Weterynaryjna

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Puzio I., Tymicki G., Predka H., Śleboda W., Sobczyńska-Wołejszo M.Role of nesfatin-1 in the metabolism of skeletal tissues Summary NUCB2/nesfatin-1, a member of the adipokine family, is a peptide hormone with pleiotropic action. It has been found in different tissues, including cartilage and bone cells. Nesfatin-1 is produced by chondrocytes, and its synthesis increases with the degree of cell differentiation and upon stimulation by pro-inflammatory cytokines, as shown in an in vitro study. An increase in serum levels of nesfatin-1 has been observed in humans with osteoarthritis, which indicates the influence of pro-inflammatory cytokines on nesfatin-1 release. On the other hand, nesfatin-1 stimulates the synthesis of pro-inflammatory cytokines by chondrocytes, which suggests its participation, together with other adipokines, in the pathogenesis and/or progression of inflammatory complications of cartilage degenerative diseases. Nesfatin-1 also promotes pre-osteoblastic cell differentiation and mineralization and inhibits macrophage differentiation towards osteoclasts. Moreover, exogenous nesfatin-1 given to ovariectomized rats reduces osteopenic changes. Therefore, it seems that nesfatin-1 may play a protective role in cartilage and bone diseases. However, further studies are required to determine whether nesfatin-1 can be used for monitoring and treatment of cartilage and bone diseases.

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Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats

Cited by 54 publications

References 54 publications

Nesfatin-1: functions and physiology of a novel regulatory peptide

Nesfatin-1: functions and physiology of a novel regulatory peptide

Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns

Role of nesfatin-1 in the metabolism of skeletal tissues

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