Melatonergic Receptors (Mt1/Mt2) as a Potential Additional Target of Novel Drugs for Depression

Boiko, D. I.; Shkodina, Anastasiia D.; Hasan, Mohammad Mehedi; Bardhan, Mainak; Kazmi, Syeda Kanza; Chopra, Hitesh; Bhutra, Prerna; Baig, Atif Amin; Skrypnіkov, A. M.

doi:10.1007/s11064-022-03646-5

Cited by 26 publications

(14 citation statements)

References 143 publications

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“…Melatonin, a neuromodulatory hormone, is cyclic and its receptors may also undergo circadian change. 62 Our findings showed a sharp decrease in Mt1 and Mt2 mRNA expression in the duodenum and colon during the night time due to stimulation by ZnONPs, and a pattern of expression might correlate with melatonin receptors distribution. One study evaluated the protective effect of melatonin against ZnONPs toxicity using C6 glial cells.…”

Section: Discussionsupporting

confidence: 50%

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

Yang¹,

Lu²,

Xia³

et al. 2023

IJN

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Purpose The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin. Methods In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase ( Aanat ), melatonin receptor1A ( Mt1 / Mtnr1a ), melatonin receptor1B ( Mt2 / Mtnr1b ), and neuropeptide Y ( Npy ) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed. Results The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat , the membrane receptors Mt1 and Mt2 and Npy during the day and night. Conclusion Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity.

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Section: Discussionsupporting

confidence: 50%

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

Yang¹,

Lu²,

Xia³

et al. 2023

IJN

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“…Excessive lighting in the dark phase leads to the perturbation of clock genes (CLOCK, PER1, PER2) in humans and rodents by increasing immune activation and producing pro-inflammatory cytokines, even in the absence of immune challenge [ 31 , 32 ]. Some proteins of the circadian oscillator, and, in particular, CLOCK, are known to be involved in the NF-κB activation [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary Supplementation with Resveratrol Attenuates Serum Melatonin Level, Pro-Inflammatory Response and Metabolic Disorder in Rats Fed High-Fructose High-Lipid Diet under Round-the-Clock Lighting

Frenkel

Черно

Kostenko³

et al. 2023

Pathophysiology

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This study aims to investigate the effect of resveratrol on systemic inflammatory response and metabolic disorder in rats fed a high-fructose high-lipid diet (HFHLD) and exposed to round-the-clock lighting (RCL). 21 adult male Wistar rats were randomly divided into 3 groups: control (group 1, n = 7); HFHLD for 8 weeks + round-the-clock lighting (RCL) (group 2, n = 7); HFHLD + RCL + Resveratrol (in a daily dose of 5 mg/kg intragastrically (group 3, n = 7). Results show that the combined effect of HFHLD and RCL reduces the serum melatonin (p < 0.001) and accelerates pro-inflammatory activities, oxidative stress, and metabolic disorder. There is a significant increase in the serum tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) (both p < 0.001), blood malondialdehyde—thiobarbituric acid adducts (MDA-TBA2) (p < 0.001), serum glucose (p < 0.01), insulin concentration, and the homeostatic model assessment insulin resistance (HOMA-IR) index (both p < 0.001), serum with very low-density lipoprotein (VLDL), and triacylglycerol (TAG) (both p < 0.001). At the same time, the decrease in the serum high-density lipoprotein (HDL) level (p < 0.001) is observed in the HFHLD + RCL group compared to the control. In the HFHLD + RCL + Resveratrol group, hypomelatonaemia (p < 0.001), pro-inflammatory actions, oxidative stress, and metabolic disorder were mitigated. Resveratrol can cause a significant rise in the serum melatonin and reduce serum TNF-α and CRP levels (both p < 0.001), blood MDA-TBA2 (p < 0.001), serum glucose (both p < 0.01), insulin concentration, and HOMA-IR (both p < 0.001), serum VLDL and TAG (both p < 0.001) compared to the group 2, while serum HDL level increases (p < 0.01). Resveratrol attenuates pro-inflammatory responses and prevents considerable metabolic disorder in rats fed HFHLD under RCL.

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“…Melatonin can be a potential course of action for novel antidepressants, which affect the concentrations of neurotrophins or neurotransmitters. In addition, they cause a reduction in the proinflammatory cytokine level in the serum [ 36 ]. The neuroprotective effect of melatonin is used in the treatment of Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotrophic lateral sclerosis, stroke, and brain trauma [ 7 , 37 ].…”

Section: The Biological Role Of Melatoninmentioning

confidence: 99%

Melatonin Treatment in Kidney Diseases

Markowska

Niemczyk

Romejko

2023

Cells

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Melatonin is a neurohormone that is mainly secreted by the pineal gland. It coordinates the work of the superior biological clock and consequently affects many processes in the human body. Disorders of the waking and sleeping period result in nervous system imbalance and generate metabolic and endocrine derangements. The purpose of this review is to provide information regarding the potential benefits of melatonin use, particularly in kidney diseases. The impact on the cardiovascular system, diabetes, and homeostasis causes melatonin to be indirectly connected to kidney function and quality of life in people with chronic kidney disease. Moreover, there are numerous reports showing that melatonin plays a role as an antioxidant, free radical scavenger, and cytoprotective agent. This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress occur, regardless of the mechanism. The administration of melatonin has a renoprotective effect and inhibits the progression of complications connected to renal failure. It is very important that exogenous melatonin supplementation is well tolerated and that the number of side effects caused by this type of treatment is low.

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Melatonergic Receptors (Mt1/Mt2) as a Potential Additional Target of Novel Drugs for Depression

Cited by 26 publications

References 143 publications

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

Dietary Supplementation with Resveratrol Attenuates Serum Melatonin Level, Pro-Inflammatory Response and Metabolic Disorder in Rats Fed High-Fructose High-Lipid Diet under Round-the-Clock Lighting

Melatonin Treatment in Kidney Diseases

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