Immunohistochemical and biomolecular identification of melatonin 1a and 1b receptors in rat vestibular nuclei

Ahn, Seong-Ki; Khalmuratova, Roza; Hah, Young‐Sool; Jeon, Sea‐Yuong; Hur, Dong Gu; Kang, Hung-Soo; Balaban, Carey D.

doi:10.1016/j.anl.2011.09.007

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…As the expression of melatonin receptors peaks at light onset, we euthanized mice at light onset . Both primary antibodies used in this study were previously used to localize melatonin receptors . Control experiments (see ) were performed to verify selectivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

“…86 Both primary antibodies used in this study were previously used to localize melatonin receptors. [50][51][52][53][54][55] Control experiments (see Methods) were performed to verify selectivity and specificity. Our results suggest that orexin neurons express MT1R, but not MT2R.…”

Section: Discussionmentioning

confidence: 99%

“…This was followed by overnight incubation in PBS + NDS and MT1R (1:50; rabbit anti‐MT1R; Abbiotec, San Diego, CA) or MT2R (goat anti‐MT2R; 1:50; Santa Cruz, Dallas, TX; or rabbit anti‐MT2R; 1:100; Novus Biological, Littleton, CO) primary antibodies. These antibodies have been previously used to detect melatonin receptors in the select brain regions . Day 2: Sections were washed and incubated with PB + NDS containing CY3‐conjugated secondary antibody (donkey anti‐rabbit for MT1R or donkey anti‐goat for MT2R; 1:500; Jackson ImmunoResearch, West Grove, PA) for 1 hour.…”

Section: Methodsmentioning

confidence: 99%

“…These antibodies have been previously used to detect melatonin receptors in the select brain regions. [50][51][52][53][54][55] Day 2: Sections were washed and incubated with PB + NDS containing CY3-conjugated secondary antibody (donkey anti-rabbit for MT1R or donkey anti-goat for MT2R; 1:500; Jackson ImmunoResearch, West Grove, PA) for 1 hour. Next, sections were washed and incubated in PBS containing 1.5% NDS and goat anti-orexin A (1:500; Santa Cruz).…”

Section: Immunofluorescencementioning

confidence: 99%

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Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Sharma

Sahota

Thakkar

2018

Journal of Pineal Research

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Melatonin promotes sleep. However, the underlying mechanisms are unknown. Orexin neurons in the perifornical lateral hypothalamus (PFH) are pivotal for wake promotion. Does melatonin promote sleep by inhibiting orexin neurons? We used C57BL/6J mice and designed 4 experiments to address this question. Experiment 1 used double-labeled immunofluorescence and examined the presence of melatonin receptors on orexin neurons. Second, mice, implanted with bilateral guides targeted toward PFH and sleep-recording electrodes, were infused with melatonin (500 pmole/50 nL/side) at dark onset (onset of active period), and spontaneous bouts of sleep-wakefulness were examined. Third, mice, implanted with bilateral guides into the PFH, were infused with melatonin (500 pmole/50 nL/side) at dark onset and euthanized 2 hours later, to examine the activation of orexin neurons using c-Fos expression in orexin neurons. Fourth, mice, implanted with PFH bilateral guides and sleep-recording electrodes, were infused with melatonin receptor antagonist, luzindole (10 pmol/50 nL/side), at light onset (onset of sleep period), and spontaneous bouts of sleep-wakefulness were examined. Our results suggest that orexin neurons express MT1, but not MT2 receptors. Melatonin infusion into the PFH, at dark onset, site-specifically and significantly increased NREM sleep (43.7%, P = .003) and reduced wakefulness (12.3%, P = .013). Local melatonin infusion at dark onset inhibited orexin neurons as evident by a significant reduction (66%, P = .0004) in the number of orexin neurons expressing c-Fos. Finally, luzindole infusion-induced blockade of melatonin receptors in PFH at sleep onset significantly increased wakefulness (44.1%, P = .015). Based on these results, we suggest that melatonin may act via the MT1 receptors to inhibit orexin neurons and promote sleep.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Immunofluorescencementioning

confidence: 99%

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Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Sharma

Sahota

Thakkar

2018

Journal of Pineal Research

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“…Messenger RNA expression of MT 1 and MT 2 receptors has been observed in the retina, SCN, thalamus, hippocampus vestibular nuclei and cerebral and cerebellar cortex. [27][28][29][30] At the level of the hippocampus, MT 2 receptors were detectable in particular on CA 3 and CA 4 pyramidal neurons, which receive glutamatergic excitatory inputs from the entorhinal cortex, whereas MT 1 receptors were predominantly expressed in CA 1 . 31 Recently, using polyclonal antibodies 32 we have pointed out the presence of MT 2 receptors in the reticular thalamus, substantia nigra (pars reticulata), supraoptic nucleus, red nucleus and CA 2 and CA 3 areas of the hippocampus.…”

Section: Where Are They?mentioning

confidence: 99%

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

Comai

Gobbi

2014

J Psychiatry Neurosci

155

126

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IntroductionMelatonin (MLT) is a neurohormone synthesized from serotonin (5-HT) and secreted foremost by the mammalian pineal gland following a distinct circadian rhythm with the acrophase during the dark phase and the nadir during the light phase in both diurnal and nocturnal species.1 A typical human adult's average daytime and nighttime levels of blood MLT are approximately 10 pg/mL and 60 pg/mL, respectively.2 Its production is controlled through the suprachiasmatic nucleus (SCN) by the photoperiod, peaking at night and dropping during the day. Melatonin is involved in numerous physiologic processes, including circadian rhythms, mood regulation, anxiety, sleep, appetite, immune responses and cardiac functions. 3,4 Most of the effects of MLT in the brain result from the activation of 2 high-affinity G-protein coupled receptors (GPCRs), MT 1 and MT 2 .5 Of note, GPCRs have a proven history of being excellent therapeutic targets. Recent market analyses indicate that 40%-50% of modern drugs and almost 25% of the top 200 best-selling drugs target GPCRs. 6 In addition to these high-affinity MLT receptors, another low-affinity MLT binding site, MT 3 , has recently been characterized as an MLT-sensitive form of the human enzyme quinone reductase 2. 7 The functional characterization of MT 1 and MT 2 receptors in target tissues is hampered by the paucity of selective MT 1 and MT 2 receptor ligands. Structural Background: Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT 1 (MEL1a) and MT 2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT 1 and MT 2 receptors. Here we have reviewed current knowledge about the implications of MT 2 receptors in brain functions. Methods: We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT 2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT 2 receptor. Results: These studies demonstrate that MT 2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT 2 receptor agonists show hypnotic and anxiolytic properties. Limitations: Studies examining the role of MT 2 receptors in psychopharmacology are still limited. Conclusion: The development of novel selective MT 2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, M...

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Neurotransmitters in the vestibular system

Balaban

2016

Handbook of Clinical Neurology

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Immunohistochemical and biomolecular identification of melatonin 1a and 1b receptors in rat vestibular nuclei

Cited by 10 publications

References 23 publications

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

Neurotransmitters in the vestibular system

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