Journal of Pineal Research

Cholestatic liver disease is characterized by disturbances in the intestinal microbiota and excessive accumulation of toxic bile acids (BA) in the liver. Melatonin (MT) can improve liver diseases. However, the underlying mechanism remains unclear. This study aimed to explore the mechanism of MT on hepatic BA synthesis, liver injury, and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and Mdr2-/- mice. MT significantly improved hepatic injury and fibrosis with a significant decrease in hepatic BA accumulation in DDC-fed and Mdr2-/- mice...

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data...

Acute effects of exogenous melatonin have been widely reported to promote sleep or induce drowsiness in human. However, testing of the hypnotic effects of melatonin in nocturnal rodents has yielded contradictory results. The latter may be associated with differences in concentration, lighting conditions, time of administration of melatonin, and possibly the type of analysis. In this study, electroencephalogram (EEG) and electromyogram were recorded in pigmented male Brown Norway rats under both light-dark (LD) and constant dark (DD) conditions...

The pineal gland has evolved from a photoreceptive organ in fish to a neuroendocrine organ in mammals. This study integrated multiple daytime single-cell RNA-seq datasets from the pineal glands of zebrafish, rats, and monkeys, providing a detailed examination of the evolutionary transition at single-cell resolution. We identified key factors responsible for the anatomical and functional transformation of the pineal gland. We retrieved and integrated daytime single-cell transcriptomic datasets from the pineal glands of zebrafish, rats, and monkeys, resulting in a total of 22 431 cells after rigorous quality filtering...

Immune-pineal axis activation is part of the assembly of immune responses. Proinflammatory cytokines inhibit the pineal synthesis of melatonin while inducing it in macrophages by mechanisms dependent on nuclear factor-κB (NF-κB) activation. Cytokines activating the Janus kinase/signal transducer and activator of transcription (STAT) pathways, such as interferon-gamma (IFN-γ) and interleukin-10 (IL-10), modulate melatonin synthesis in the pineal, bone marrow (BM), and spleen. The stimulatory effect of IFN-γ upon the pineal gland depends on STAT1/NF-κB interaction, but the mechanisms controlling IL-10 effects on melatonin synthesis remain unclear...

Stroke is the leading cause of death and disability worldwide. Novel and effective therapies for ischemic stroke are urgently needed. Here, we report that melatonin receptor 1A (MT1) agonist ramelteon is a neuroprotective drug candidate as demonstrated by comprehensive experimental models of ischemic stroke, including a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia in vivo, organotypic hippocampal slice cultures ex vivo, and cultured neurons in vitro; the neuroprotective effects of ramelteon are diminished in MT1-knockout (KO) mice and MT1-KO cultured neurons...

Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs...

This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0...

Evidence suggests that the neuroprotective effects of melatonin involve both receptor-dependent and -independent actions. However, little is known about the effects of melatonin receptor activation on the kainate (KA) neurotoxicity. This study examined the effects of repeated post-KA treatment with ramelteon, a selective agonist of melatonin receptors, on neuronal loss, cognitive impairment, and depression-like behaviors following KA-induced seizures. The expression of melatonin receptors decreased in neurons, whereas it was induced in astrocytes 3 and 7 days after seizures elicited by KA (0...

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA-binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region...

Besides its role in the circadian rhythm, the pineal gland hormone melatonin (MLT) also possesses antiepileptogenic, antineoplastic, and cardioprotective properties, among others. The dosages necessary to elicit beneficial effects in these diseases often far surpass physiological concentrations. Although even high doses of MLT are considered to be largely harmless to humans, the possible side effects of pharmacological concentrations are so far not well investigated. In the present study, we report that pharmacological doses of MLT (3 mM) strongly altered the electrophysiological characteristics of cultured primary mouse cerebellar granule cells (CGCs)...

No abstract text is available yet for this article.

Normal tension glaucoma (NTG) is referred to as a progressive degenerative disorder of the retinal ganglion cells (RGCs), resulting in nonreversible visual defects, despite intraocular pressure levels within the statistically normal range. Current therapeutic strategies for NTG yield limited benefits. Excitatory amino acid carrier 1 (EAAC1) knockout (EAAC1-/- ) in mice has been shown to induce RGC degeneration without elevating intraocular pressure, mimicking pathological characteristics of NTG. In this study, we explored whether daily oral administration of melatonin could block RGCs loss and prevent retinal morphology and function defects associated with EAAC1 deletion...

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus...

Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0 ) synthesis, reduced estradiol (E2 ), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas...

No abstract text is available yet for this article.

Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells...

Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1-/- ) were examined by phenotypic tests and light and electron microscopy...

No abstract text is available yet for this article.

During gestation, the developing fetus relies on precise maternal circadian signals for optimal growth and preparation for extrauterine life. These signals regulate the daily delivery of oxygen, nutrients, hormones, and other biophysical factors while synchronizing fetal rhythms with the external photoperiod. However, modern lifestyle factors such as light pollution and shift work can induce gestational chronodisruption, leading to the desynchronization of maternal and fetal circadian rhythms. Such disruptions have been associated with adverse effects on cardiovascular, neurodevelopmental, metabolic, and endocrine functions in the fetus, increasing the susceptibility to noncommunicable diseases (NCDs) in adult life...