Journal of Pineal Research最新文献

{"title":"Melatonin treatment improves ventricular conduction via upregulation of Nav1.5 channel proteins and sodium current in the normal rat heart","authors":"Aleksandra V. Durkina,&nbsp;Olesya G. Bernikova,&nbsp;Mikhail A. Gonotkov,&nbsp;Natalia J. Mikhaleva,&nbsp;Ksenia A. Sedova,&nbsp;Inna A. Malykhina,&nbsp;Vladislav S. Kuzmin,&nbsp;Ilya O. Velegzhaninov,&nbsp;Jan E. Azarov","doi":"10.1111/jpi.12798","DOIUrl":"https://doi.org/10.1111/jpi.12798","url":null,"abstract":"<p>Melatonin treatment was reported to reduce the risk of cardiac arrhythmias, and crucial for this antiarrhythmic action was the effect of melatonin on activation spread. The aim of the present study was evaluation of the mechanisms of this activation enhancement. Experiments were performed in a total of 123 control and melatonin-treated (10 mg/kg, daily, for 7 days) male Wistar rats. In epicardial mapping studies (64 leads, interlead distance 0.5 mm) in the anesthetized animals, activation times (ATs) were determined in each lead as <i>dV</i>/<i>dt</i> minimum during QRS complex under sinus rhythm. Epicardial pacing was performed to measure conduction velocity (CV) across the mapped area. Average left ventricular ATs were shorter in the treated animals as compared to the controls, whereas the minimal epicardial ATs indicating the duration of activation propagation via the ventricular conduction system did not differ between the groups. CV was higher in the treated groups indicating that melatonin affected conduction via contractile myocardium The area of Cx43-derived fluorescence, as well as the expression of Cx43 protein, was similar in ventricles in the control and melatonin-treated groups. Expression of Gja1 gene transcripts encoding Cx43, was increased in the last group. An uncoupling agent octanol modified myocardial conduction properties (time of activation, action potential upstroke velocity, passive electrotonic phase duration) similarly in both groups. On the other hand, the expression of both <i>Scn5a</i> gene transcripts encoding Nav1.5 proteins, as well as peak density of transmembrane sodium current were increased in the ventricular myocytes from the melatonin-treated animals. Thus, a week-long melatonin treatment caused the increase of conduction velocity via enhancement of sodium channel proteins expression and increase of sodium current in the ventricular myocytes.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6083147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The phytomelatonin receptor PMTR1 regulates seed development and germination by modulating abscisic acid homeostasis in Arabidopsis thaliana","authors":"Xiaoming Yin,&nbsp;Ya-Li Bai,&nbsp;Chunyan Gong,&nbsp;Wenli Song,&nbsp;Yan Wu,&nbsp;Tiantian Ye,&nbsp;Yu-Qi Feng","doi":"10.1111/jpi.12797","DOIUrl":"https://doi.org/10.1111/jpi.12797","url":null,"abstract":"<p>Melatonin is known to involve multiple physiological actions in plants. Herein, we found that exogenous melatonin inhibited the Arabidopsis seedling growth through the elevated abscisic acid (ABA) levels, and the elevated ABA was ascribed to the upregulation of 9-<i>cis</i>-epoxycarotenoid dioxygenase genes (<i>NCEDs</i>) in the ABA biosynthesis pathway. We also found that the overexpression lines of the melatonin receptor gene <i>PMTR1</i> (also known as <i>Cand2</i>) yielded smaller seeds and germinated slower than the wild type, whereas <i>PMTR1</i>-knockout mutants produced larger seeds and germinated faster than the wild type. During the seed development, the accumulation peak of ABA was higher in the <i>PMTR1-</i>knockout mutant, while it was lower in <i>the PMTR1</i>-overexpression line than that in the wild type. In the dry seeds and imbibed seeds, the <i>PMTR1</i>-overexpression line accumulated higher ABA levels, while the <i>PMTR1-</i>knockout contained less ABA than the wild type. In summary, our findings suggest that PMTR1 is involved in ABA-mediated seed development and germination in Arabidopsis.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5792677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic ablation of the Bsx homeodomain transcription factor in zebrafish: Impact on mature pineal gland morphology and circadian behavior","authors":"Mikkel Bloss Carstensen,&nbsp;Adar Medvetzky,&nbsp;Alon Weinberger,&nbsp;Wolfgang Driever,&nbsp;Yoav Gothilf,&nbsp;Martin Fredensborg Rath","doi":"10.1111/jpi.12795","DOIUrl":"https://doi.org/10.1111/jpi.12795","url":null,"abstract":"<p>The pineal gland is a neuroendocrine structure in the brain, which produces and secretes the hormone melatonin at nighttime and is considered a key element in the circadian clock system. Early morphogenesis of the gland is controlled by a number of transcription factors, some of which remain active in adult life. One of these is the brain-specific homeobox (Bsx), a highly conserved homeodomain transcription factor with a developmental role in the pineal gland of several species, including zebrafish, and regulatory roles in mature pinealocytes of the rat. To determine the role of Bsx in circadian biology, we here examined the effects of a <i>bsx</i> loss-of-function mutation on the pineal gland in adult zebrafish and on behavioral circadian rhythms in larvae. In pineal cell type-specific Gfp/Egfp reporter zebrafish lines, we did not detect fluorescence signals in the pineal area of homozygous (<i>bsx</i>^−/−) mutants. Interestingly, a nonpigmented area on the dorsal surface of the head above the gland, known as the pineal window, was pigmented in the homozygous mutants. Furthermore, a structure corresponding to the pineal gland was not detectable in the midline of the adult brain in histological sections analyzed by Nissl staining and S-antigen immunohistochemistry. Moreover, the levels of pineal transcripts were greatly reduced in <i>bsx</i>^−/− mutants, as revealed by quantitative real-time polymerase chain reaction analysis. Notably, analysis of locomotor activity at the larval stage revealed altered circadian rhythmicity in the <i>bsx</i> mutants with periods and phases similar to wildtype, but severely reduced amplitudes in locomotor activity patterns. Thus, Bsx is essential for full development of the pineal gland, with its absence resulting in a phenotype of morphological pineal gland ablation and disrupted circadian behavior.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5714092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin and aggressive behavior: A systematic review of the literature on preclinical and clinical evidence","authors":"Pasquale Paribello,&nbsp;Mirko Manchia,&nbsp;Marta Bosia,&nbsp;Federica Pinna,&nbsp;Bernardo Carpiniello,&nbsp;Stefano Comai","doi":"10.1111/jpi.12794","DOIUrl":"https://doi.org/10.1111/jpi.12794","url":null,"abstract":"<p>The melatonin system and circadian disruption have well-established links with aggressive behaviors; however, the biological underpinnings have not been thoroughly investigated. Here, we aimed at examining the current knowledge regarding the neurobiological and psychopharmacological involvement of the melatonin system in aggressive/violent behaviors. To this end, we performed a systematic review on Embase and Pubmed/MEDLINE of preclinical and clinical evidence linking the melatonin system, melatonin, and melatoninergic drugs with aggressive/violent behaviors. Two blinded raters performed an independent screening of the relevant literature. Overall, this review included 38 papers distributed between clinical and preclinical models. Eleven papers specifically addressed the existing evidence in rodent models, five in fish models, and 21 in humans. The data indicate that depending on the species, model, and timing of administration, melatonin may exert a complex influence on aggressive/violent behaviors. Particularly, the apparent contrasting findings on the link between the melatonin system and aggression/violence (with either increased, no, or decreased effect) shown in preclinical models underscore the need for further research to develop more accurate and fruitful translational models. Likewise, the significant heterogeneity found in the results of clinical studies does not allow yet to draw any firm conclusion on the efficacy of melatonin or melatonergic drugs on aggressive/violent behaviors. However, findings in children and in traits associated with aggressive/violent behavior, including irritability and anger, are emerging and deserve empirical attention given the low toxicity of melatonin and melatonergic drugs.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5802056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin delays dark-induced leaf senescence by inducing miR171b expression in tomato","authors":"Kaixin Wang,&nbsp;Shuyu Cai,&nbsp;Qufan Xing,&nbsp;Zhenyu Qi,&nbsp;Vasileios Fotopoulos,&nbsp;Jingquan Yu,&nbsp;Jie Zhou","doi":"10.1111/jpi.12792","DOIUrl":"https://doi.org/10.1111/jpi.12792","url":null,"abstract":"<p>Melatonin functions in multiple aspects of plant growth, development, and stress response. Nonetheless, the mechanism of melatonin in plant carbon metabolism remains largely unknown. In this study, we investigated the influence of melatonin on the degradation of starch in tomato leaves. Results showed that exogenous melatonin attenuated carbon starvation-induced chlorophyll degradation and leaf senescence. In addition, melatonin delayed leaf starch degradation and inhibited the transcription of starch-degrading enzymes after sunset. Interestingly, melatonin-alleviated symptoms of leaf senescence and starch degradation were compromised when the first key gene for starch degradation, <i>α-glucan water dikinase</i> (<i>GWD</i>), was overexpressed. Furthermore, exogenous melatonin significantly upregulated the transcript levels of several microRNAs, including <i>miR171b</i>. Crucially, the <i>GWD</i> gene was identified as a target of <i>miR171b</i>, and the overexpression of <i>miR171b</i> ameliorated the carbon starvation-induced degradation of chlorophyll and starch, and inhibited the expression of the <i>GWD</i> gene. Taken together, these results demonstrate that melatonin promotes plant tolerance against carbon starvation by upregulating the expression of <i>miR171b</i>, which can directly inhibit <i>GWD</i> expression in tomato leaves.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5883243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α2β1 expression","authors":"Huai-Ching Tai,&nbsp;Shih-Wei Wang,&nbsp;Sanskruti Swain,&nbsp;Liang-Wei Lin,&nbsp;Hsiao-Chi Tsai,&nbsp;Shan-Chi Liu,&nbsp;Hsi-Chin Wu,&nbsp;Jeng-Hung Guo,&nbsp;Chun-Lin Liu,&nbsp;Yu-Wei Lai,&nbsp;Tien-Huang Lin,&nbsp;Shun-Fa Yang,&nbsp;Chih-Hsin Tang","doi":"10.1111/jpi.12793","DOIUrl":"https://doi.org/10.1111/jpi.12793","url":null,"abstract":"<p>Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (<i>N</i>-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT₁ receptor, which effectively inhibits integrin α₂β₁ expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5683071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24-h melatonin rhythm with antiphasic daytime and nighttime peaks","authors":"Jingyi Qian,&nbsp;Christopher J. Morris,&nbsp;Andrew J. K. Phillips,&nbsp;Peng Li,&nbsp;Shadab A. Rahman,&nbsp;Wei Wang,&nbsp;Kun Hu,&nbsp;Josephine Arendt,&nbsp;Charles A. Czeisler,&nbsp;Frank A. J. L. Scheer","doi":"10.1111/jpi.12791","DOIUrl":"https://doi.org/10.1111/jpi.12791","url":null,"abstract":"<p>The daily rhythm of plasma melatonin concentrations is typically unimodal, with one broad peak during the circadian night and near-undetectable levels during the circadian day. Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly-controlled simulated night shift protocol with 12-h inverted behavioral/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (<i>p</i> &lt; .0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation, therefore, challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (<i>p</i> = .002), but not with the degree of light-induced melatonin suppression during nighttime wakefulness (<i>p</i> = .92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (<i>p</i> = .002 and <i>p</i> = .006, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24-h glucose and insulin levels during the night shift protocol (<i>p</i> = .014 and <i>p</i> = .027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5761011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective","authors":"Alec Sevilla,&nbsp;Jérémy Chéret,&nbsp;Radomir M. Slominski,&nbsp;Andrzej T. Slominski,&nbsp;Ralf Paus","doi":"10.1111/jpi.12790","DOIUrl":"https://doi.org/10.1111/jpi.12790","url":null,"abstract":"<p>The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms of action, which include the regulation of vertebrate pigmentation. Although first discovered through its potent skin-lightening effects in amphibians, melatonin's role in human skin and hair follicle pigmentation and its impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding of this role, we specifically examine its impact on melanogenesis, oxidative biology, mitochondrial function, melanocyte senescence, and pigmentation-related clock gene activity, with emphasis on human skin, yet without ignoring instructive pointers from nonhuman species. Given the strict dependence of melanocyte functions on the epithelial microenvironment, we underscore that melanocyte responses to melatonin are best interrogated in a physiological tissue context. Current evidence suggests that melatonin and some of its metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) and melanocyte proliferation by stimulating melatonin membrane receptors (MT1, MT2). We discuss whether putative melanogenesis-inhibitory effects of melatonin may occur via activation of Nrf2-mediated PI3K/AKT signaling, estrogen receptor-mediated and/or melanocortin-1 receptor- and cAMP-dependent signaling, and/or via melatonin-regulated changes in peripheral clock genes that regulate human melanogenesis, namely <i>Bmal1</i> and <i>Per1</i>. Melatonin and its metabolites also accumulate in melanocytes where they exert net cyto- and senescence-protective as well as antioxidative effects by operating as free radical scavengers, stimulating the synthesis and activity of ROS scavenging enzymes and other antioxidants, promoting DNA repair, and enhancing mitochondrial function. We argue that it is clinically and biologically important to definitively clarify whether melanocyte cell culture-based observations translate into melatonin-induced pigmentary changes in a physiological tissue context, that is, in human epidermis and hair follicles ex vivo, and are confirmed by clinical trial results. After defining major open questions in this field, we close by suggesting how to begin answering them in clinically relevant, currently available preclinical in situ research models.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6041755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of melatonin receptor 1 by CRISPR-Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model","authors":"Hanseul Park,&nbsp;Jongpil Kim","doi":"10.1111/jpi.12787","DOIUrl":"https://doi.org/10.1111/jpi.12787","url":null,"abstract":"<p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of neurotoxic beta-amyloid (Aβ) in the brain. Melatonin receptors have been reported to associate with aging and AD, and their expression decreased with the progression of AD. As an alternative to AD treatment, overexpression of melatonin receptors may lead to melatonin-like effects to treat alleviate the symptoms of AD. Here, we successfully activated the type 1 melatonin receptor (Mt1) in vivo brain using a Cas9 activator as a novel AD therapeutic strategy. The Cas9 activator efficiently activated the endogenous Mt1 gene in the brain. Activation of Mt1 via Cas9 activators modulated anti-amyloidogenic and anti-inflammatory roles in 5xFAD AD mice brain. Moreover, activation of Mt1 with the CRISPR/Cas9 activator improved cognitive deficits in an AD model. These results demonstrated the therapeutic potential of melatonin receptor activation via CRISPR/Cas9 activator for AD.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6042727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High sensitivity of melatonin suppression response to evening light in preschool-aged children","authors":"Lauren E. Hartstein,&nbsp;Cecilia Diniz Behn,&nbsp;Lameese D. Akacem,&nbsp;Nora Stack,&nbsp;Kenneth P. Wright Jr.,&nbsp;Monique K. LeBourgeois","doi":"10.1111/jpi.12780","DOIUrl":"https://doi.org/10.1111/jpi.12780","url":null,"abstract":"<p>Light at night in adults suppresses melatonin in a nonlinear intensity-dependent manner. In children, bright light of a single intensity before bedtime has a robust melatonin suppressing effect. To our knowledge, whether evening light of different intensities is related to melatonin suppression in young children is unknown. Healthy, good-sleeping children (n = 36; 3.0–4.9 years; 39% male) maintained a stable sleep schedule for 7 days followed by a 29.5-h in-home dim-light circadian assessment (~1.5 lux). On the final night of the protocol, children received a 1-h light exposure (randomized to one of 15 light levels, ranging 5–5000 lux, with ≥2 participants assigned to each light level) in the hour before habitual bedtime. Salivary melatonin was measured to calculate the magnitude of melatonin suppression during light exposure compared with baseline levels from the previous evening, as well as the degree of melatonin recovery 50 min after the end of light exposure. Melatonin levels were suppressed between 69.4% and 98.7% (<i>M</i> = 85.4 ± 7.2%) during light exposure across the full range of intensities examined. Overall, we did not observe a light intensity-dependent melatonin suppression response; however, children exposed to the lowest quartile of light intensities (5–40 lux) had an average melatonin suppression (77.5 ± 7.0%) which was significantly lower than that observed at each of the three higher quartiles of light intensities (86.4 ± 5.6%, 89.2 ± 6.3%, and 87.1 ± 5.0%, respectively). We further found that melatonin levels remained below 50% baseline for at least 50 min after the end of light exposure for the majority (62%) of participants, and recovery was not influenced by light intensity. These findings indicate that preschool-aged children are highly sensitive to light exposure in the hour before bedtime and suggest the lighting environment may play a crucial role in the development and the maintenance of behavioral sleep problems through impacts on the circadian timing system.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"72 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5761962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}