Melatonin receptor deficiency decreases and temporally shifts ecto-5′-nucleotidase mRNA levels in mouse prosencephalon

Homola, Moran; Pfeffer, Martina; Robson, Simon C.; Fischer, Claudia; Zimmermann, Herbert; Korf, Horst‐Werner

doi:10.1007/s00441-016-2378-x

Cited by 7 publications

(7 citation statements)

References 56 publications

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“…Thus, the increase in P2X3 and P2X4 during the dark phase is coincident with the extracellular ATP accumulation in the SCN and precedes the moderate increase in P2Y2, P2Y12, P2Y14 and P2Y6. Ectonucleotidases, which show a circadian rhythm in various brain regions (Homola et al 2016 ), rapidly hydrolyze extracellular ATP to ADP, AMP and adenosine (Yegutkin 2008 ), a process that terminates P2 activation and prevents receptor desensitization (Junger 2011 ). The increase in P2Y protein expression during the early to mid-light phase might be a compensatory mechanism in response to the decline in agonist levels.…”

Section: Discussionmentioning

confidence: 99%

Time-of-day-dependent expression of purinergic receptors in mouse suprachiasmatic nucleus

et al. 2017

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Purinergic P2X and P2Y receptors are involved in mediating intercellular signalling via purines such as adenosine triphosphate (ATP). P2X and P2Y receptors have been implicated in numerous body functions including learning, memory and sleep. All of these body functions show time-of–day-dependent variations controlled by the master circadian oscillator located in the suprachiasmatic nucleus (SCN). Evidence exists for a role of purinergic signalling in intercellular coupling within SCN. However, few studies have been performed on the expression of purinergic receptors in SCN. Therefore, we analyse the expression of seven P2X (P2X1–7) and eight P2Y (P2Y1–2, 4, 6, 11–14) receptors in mouse SCN and address their time-of-day-dependent variation by using immunohistochemistry and real-time polymerase chain reaction. At the early light phase, P2X and P2Y receptors show a low to moderate, homogenously distributed immunoreaction throughout SCN. P2Y13 reveals strong immunoreaction in fibres within the core region of SCN. From the fifteen analysed P2 receptors, seven exhibit a time-of-day-dependent variation in SCN. P2X1 immunoreaction is very low in the early light phase with a minor increase at the end of the dark phase. P2X4 immunoreaction strongly increases during the dark phase in soma cells in the core region and in a dense network of fibres in the shell region of SCN. P2X3 immunoreaction is moderately elevated during the dark phase. Conversely, immunoreaction for P2Y2, P2Y12 and P2Y14 moderately increases at the early light phase and P2Y6 immunoreaction displays a moderate increase at the mid-light phase. Thus, this study demonstrates a time-of-day-dependent variation of P2 receptors in mouse SCN.Electronic supplementary materialThe online version of this article (doi:10.1007/s00441-017-2634-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Time-of-day-dependent expression of purinergic receptors in mouse suprachiasmatic nucleus

et al. 2017

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“…Ectonucleotidases hydrolyze ATP to ADP and ultimately to adenosine [51] and, therefore, play a pivotal role in purinergic signal transmission as they control their availability at purinergic P2 receptors [52]. In various prosencephalic brain regions, ectonucleotidases show a time-of-day-dependent expression pattern, which is modulated by melatonin [53], and is mediated by MT1 and MT2 receptors [54] suggesting the melatoninergic signaling as an interface between the purinergic system and the circadian system in general [54]. However, little is known about the role of melatonin on the purinergic system in the retina.…”

Section: Purinergic Signaling Within the Retinamentioning

confidence: 99%

“…Thus, extracellular ATP might play an important role in intercellular communication within the SCN. Moreover, ectonucleotidases show a circadian rhythm in various brain regions [54]. They rapidly hydrolyze extracellular ATP to its metabolites: ADP, AMP, and adenosine [91].…”

Section: Purinergic Signaling Within the Scnmentioning

confidence: 99%

The Role of Purinergic Receptors in the Circadian System

Ali

Avakian

Gall

2020

IJMS

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The circadian system is an internal time-keeping system that synchronizes the behavior and physiology of an organism to the 24 h solar day. The master circadian clock, the suprachiasmatic nucleus (SCN), resides in the hypothalamus. It receives information about the environmental light/dark conditions through the eyes and orchestrates peripheral oscillators. Purinergic signaling is mediated by extracellular purines and pyrimidines that bind to purinergic receptors and regulate multiple body functions. In this review, we highlight the interaction between the circadian system and purinergic signaling to provide a better understanding of rhythmic body functions under physiological and pathological conditions.

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“…Indeed, melatonin deficiency or the deletion of both melatonin receptors has been shown to decrease the stability of activity rhythms in mice as compared to mice with an intact melatoninergic system ( Pfeffer et al, 2017 ). Also, the daytime activity has been shown to be slightly higher in melatonin-deficient C57Bl mice as compared to melatonin-proficient C3H mice and melatonin-proficient C3H mice that lack both MT receptor subtypes ( Fischer et al, 2017 ; Homola et al, 2016 ). However, under semi-natural conditions the activity rhythms of the melatonin-deficient C57Bl mice appeared more stable as compared to the melatonin-proficient C3H animals ( Metzger et al, 2020 ; Figure 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Differences in the rhythmic ectonucleotidase mRNA expression between melatonin-proficient C3H and melatonin-deficient C57Bl mice are present in several brain structures ( Homola et al, 2015 ). These differences in the rhythmic ectonucleotidase mRNA expression appeared to depend on the MT2 receptor subtype ( Homola et al, 2016 ). The impact of the MT2 receptor on the elevation of ectonucleotidase RNA levels at night-time might be of relevance since this receptor is suggested to play an important role of in sleep regulation ( Ochoa-Sanchez et al, 2011 ; Comai and Gobbi, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of the Melatoninergic System in Circadian and Seasonal Rhythms—Insights From Different Mouse Strains

et al. 2022

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The melatoninergic system comprises the neurohormone melatonin and its molecular targets. The major source of melatonin is the pineal organ where melatonin is rhythmically produced during darkness. In mammals, melatonin biosynthesis is controlled by the central circadian rhythm generator in the suprachiasmatic nucleus (SCN) and photoreceptors in the retina. Melatonin elicits its function principally through two specific receptors called MT1 and MT2. MT1 is highly expressed in the SCN and the hypophysial pars tuberalis (PT), an important interface for control of seasonal functions. The expression of the MT2 is more widespread. The role of the melatoninergic system in the control of seasonal functions, such as reproduction, has been known for more than 4 decades, but investigations on its impact on the circadian system under normal (entrained) conditions started 2 decades later by comparing mouse strains with a fully functional melatoninergic system with mouse strains which either produce insufficient amounts of melatonin or lack the melatonin receptors MT1 and MT2. These studies revealed that an intact melatoninergic system is not required for the generation or maintenance of rhythmic behavior under physiological entrained conditions. As shown by jet lag experiments, the melatoninergic system facilitated faster re-entrainment of locomotor activity accompanied by a more rapid adaptation of the molecular clock work in the SCN. This action depended on MT2. Further studies indicated that the endogenous melatoninergic system stabilizes the locomotor activity under entrained conditions. Notably, these effects of the endogenous melatoninergic system are subtle, suggesting that other signals such as corticosterone or temperature contribute to the synchronization of locomotor activity. Outdoor experiments lasting for a whole year indicate a seasonal plasticity of the chronotype which depends on the melatoninergic system. The comparison between mice with an intact or a compromised melatoninergic system also points toward an impact of this system on sleep, memory and metabolism.

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Melatonin receptor deficiency decreases and temporally shifts ecto-5′-nucleotidase mRNA levels in mouse prosencephalon

Cited by 7 publications

References 56 publications

Time-of-day-dependent expression of purinergic receptors in mouse suprachiasmatic nucleus

Time-of-day-dependent expression of purinergic receptors in mouse suprachiasmatic nucleus

The Role of Purinergic Receptors in the Circadian System

The Role of the Melatoninergic System in Circadian and Seasonal Rhythms—Insights From Different Mouse Strains

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