Journal of Pineal Research最新文献

The immune response to bacterial infection demonstrates circadian rhythmicity, with heightened antibacterial immunity often observed during the daytime. This circadian-gated immune response is believed to have evolved to synchronize peak antibacterial immunity with the increased threat of infection when active. Using a larval zebrafish infection model, we have previously shown that light has a positive effect on antibacterial immunity, with enhanced survival and neutrophil recruitment observed when infections are delivered during the light phase. However, the specific contribution of the light-detecting pineal gland and its principal hormone, melatonin, to this circadian immune response has not been investigated. Here, we examined whether the pineal gland modulates the host response to bacterial infection in a time-of-day–dependent manner by targeted ablation of the pineal gland. To generate pineal gland-deficient larvae we created the transgenic zebrafish line Tg(exorh:YFP-NTR2.0) that restricts expression of the highly efficient nitroreductase variant NTR2.0 to pinealocytes, enabling metronidazole-mediated pinealectomy. We also analyzed larvae lacking the brain-specific homeobox (bsx) gene, that encodes a transcription factor essential for pineal gland development. Both approaches resulted in complete loss of the pineal gland, confirmed by live imaging, the absence of arylalkylamine N-acetyltransferase 2 (aanat2) expression and diminished melatonin production. Pineal gland-deficient larvae exhibited normal survival and neutrophil recruitment when infected during the light phase, indicating that daytime immune defenses can be maintained independently of the pineal gland. In contrast, infection of pineal gland-deficient larvae during the dark phase led to significantly reduced survival, which correlated with impaired neutrophil recruitment to the infection site. These findings demonstrate that the pineal gland plays an important role in supporting nighttime antibacterial immunity in larval zebrafish.

The present study investigates the impact of two missense SNPs in the human melanopsin gene OPN4 -I394T (rs1079610) and P10L (rs2675703)- on non-image-forming (NIF) physiological and behavioural outputs in healthy young adults under real-world conditions. Twenty-five healthy university students were genotyped and analysed under a C-allele dominant model for I394T and a T-allele dominant model for P10L. Over 8 days, participants underwent ambulatory monitoring of wrist skin temperature (WT), sleep, activity and light exposure, together with salivary melatonin assessment under five home-based lighting/time conditions and pupillary light reflex testing. I394T-C carriers exhibited a phase delay in habitual sleep and WT rhythms, reduced WT amplitude, greater internal desynchronization, and lower nocturnal melatonin concentrations under dim light compared to the TT group. Although behavioural and peripheral rhythms were delayed, circadian phase (DLMO) remained preserved, resulting in an increased phase angle of entrainment. On free days, they also showed greater melatonin suppression despite similar light exposure. In contrast, the P10L-T allele was not associated with significant differences in ambulatory, hormonal, or pupillary outcomes. Overall, the I394T variant, but not P10L, significantly associates with NIF physiology in young adults, likely by affecting the coupling between environmental light and downstream circadian outputs, independently of circadian phase. These findings also suggest that I394T-C carriers exhibit features of the circadian phenotype commonly observed in older cohorts, including reduced rhythm robustness and lower melatonin levels, and support a role for this variant in interindividual differences in light sensitivity and circadian function.

Melatonin is synthesised from tryptophan by the sequential action of enzymes that are highly expressed in the pineal gland. Homeobox gene-encoded transcription factors typically control organ development; however, a set of homeobox genes is strongly expressed in the adult pineal gland. Previous in vitro experiments revealed that knockdown of homeobox genes in rat pinealocyte cultures reduced expression of melatonin-synthesising enzymes. Until now, it was not possible to determine the impact of homeobox genes on melatonin synthesis in vivo, which is needed to evaluate physiological functions. Using the cone-rod homeobox (Crx) gene as an example, we therefore developed an experimental pipeline to deliver short-hairpin RNA, via adeno-associated viral vectors, into the pineal gland of adult rats. This approach enabled us to selectively reduce Crx expression in the mature pineal gland, which we confirmed at both the transcript and protein levels. We employed a common approach in pharmacology to correlate Crx knockdown with the expression level of the tagged fluorescent reporter, which provided a quantitative basis to define data exclusion/inclusion criteria. Our efforts confirmed that knockdown of Crx in vivo reduced the expression of two melatonin-synthesising enzymes, namely tryptophan hydroxylase 1 and acetylserotonin O-methyltransferase, consistent with in vitro data. Furthermore, knockdown of pineal Crx significantly reduced nighttime plasma melatonin levels. Our work demonstrates a method through which knockdown of target genes in the rat pineal gland can be achieved without the need for transgenic models.

Climate change increasingly exposes crops to overlapping abiotic and biotic stresses, creating a need for regulatory strategies that improve stress tolerance without imposing unnecessary fitness costs under favorable conditions. Melatonin has been widely associated with plant responses to drought, salinity, temperature extremes, oxidative stress, and pathogen challenge, where it contributes to redox balance, hormone crosstalk, and stress-responsive gene regulation. However, the benefits of melatonin appear to depend strongly on when, where, and to what extent it is produced. In this review, we examine melatonin biosynthesis and function from a promoter-centered perspective, focusing on how stress-associated signals may regulate the core biosynthetic genes TDC, T5H, SNAT, and ASMT/COMT across tissues and stress contexts. Because direct functional validation of specific promoter architectures in plant melatonin biosynthesis genes remains limited, this review presents the promoter-centered model as a hypothesis-generating framework rather than a fully established regulatory mechanism. Here, we argue that the melatonin-mediated stress tolerance depends primarily on regulated, context-dependent pathway activation rather than constitutive pathway enhancement. We therefore discuss how current knowledge of stress signaling, cis-regulatory organization, and genome editing can be used to frame future efforts in promoter engineering of melatonin biosynthesis genes. Throughout, we distinguish established findings from forward-looking hypotheses and highlight key experimental questions that must be addressed before these concepts can be translated into crop improvement.

EXPRESSION OF CONCERN: L. Knani, D. Bartolini, S. Kechiche, C. Tortoioli, G. Murdolo, M. Moretti, I. Messaoudi, R. J. Reiter, and F. Galli, “Melatonin Prevents Cadmium-Induced Bone Damage: First Evidence on an Improved Osteogenic/Adipogenic Differentiation Balance of Mesenchymal Stem Cells as Underlying Mechanism,” Journal of Pineal Research 67, no. 3 (2019): e12597, https://doi.org/10.1111/jpi.12597.

This Expression of Concern is for the above article, published online on 24 July 2019 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley & Sons Ltd. A report on PubPeer [1] indicated that the image in Figure 3A overlaps with the image in Figure 3D. Additional investigation by the publisher found a potential error where the magnified panels for CD 0.5 µmol/L, MLT 50 nmol/L, and MOLT + CD in Figure 6B did not match up to the panels at lower magnification.

The authors responded to an inquiry by the publisher, presented original data, and requested to issue a correction. The authors also reported that the panels labelling in Figure 6B contain an error in that the magnification is supposed to be 200x and 400x, rather than 20x and 40x as indicated in the figure.

A review by the publisher of the original data supplied by the authors found that not all data could be verified. This Expression of Concern has been published in order to inform and alert readers about the concerns of image overlap in Figure 3. The authors disagree with the Expression of Concern and maintain that the errors do not affect the results or conclusions of the article.

Reference

1. René Aquarius and Illex Illecebrosus. Comments on “Melatonin Prevents Cadmium-Induced Bone Damage: First Evidence on an Improved Osteogenic/Adipogenic Differentiation Balance of Mesenchymal Stem Cells as Underlying Mechanism,” PubPeer, May 2024, https://pubpeer.com/publications/B83900A89D8ECE0843DD89860F792D.

RETRACTION: Y. Wei, Y. Bai, X. Cheng, B. Zhu, R. J. Reiter, and H. Shi, “The Dual Roles of Melatonin Biosynthesis Enzymes in the Coordination of Melatonin Biosynthesis and Autophagy in Cassava,” Journal of Pineal Research 69, no. 1 (2020): e12652, https://doi.org/10.1111/jpi.12652.

The above article, published online on 23 March 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley & Sons Ltd. A report on PubPeer [1] indicated that the pTRV and pTRV-MeASMT3 images in Figure 3D had been duplicated and presented as different samples in Figure 7B following rotation and further alteration. Additionally, several samples presented in Figure 4 contained overlapping or duplicated images. These concerns were confirmed by the publisher.

The authors responded to an inquiry by the publisher and reported that an additional image duplication had occurred in between Figures 6C and 7C, in addition to the other errors. They reported that the duplications were due to mistakes during manuscript preparation. While the authors presented original as well as repeat data with the intention of correcting these errors, the authors did not provide a satisfactory explanation for the evidence of image rotation and alteration of images between Figures 3 and 7. Therefore, the publisher and the editor have lost confidence in the results and the conclusions, and the article must be retracted. The authors agree with the retraction.