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Journal of Pineal Research Apr 2021The human pineal gland regulates day-night dynamics of multiple physiological processes, especially through the secretion of melatonin. Using mass-spectrometry-based...
The human pineal gland regulates day-night dynamics of multiple physiological processes, especially through the secretion of melatonin. Using mass-spectrometry-based proteomics and dedicated analysis tools, we identify proteins in the human pineal gland and analyze systematically their variation throughout the day and compare these changes in the pineal proteome between control specimens and donors diagnosed with autism. Results reveal diverse regulated clusters of proteins with, among others, catabolic carbohydrate process and cytoplasmic membrane-bounded vesicle-related proteins differing between day and night and/or control versus autism pineal glands. These data show novel and unexpected processes happening in the human pineal gland during the day/night rhythm as well as specific differences between autism donor pineal glands and those from controls.
Topics: Autistic Disorder; Case-Control Studies; Circadian Rhythm; Humans; Pineal Gland; Protein Interaction Maps; Proteins; Proteome; Proteomics; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Time Factors
PubMed: 33368564
DOI: 10.1111/jpi.12713 -
Frontiers in Aging Neuroscience 2022Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly patients after operation. It will prolong the length of... (Review)
Review
Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly patients after operation. It will prolong the length of stay, reduce the independence and quality of daily life, and increase the risk of death. However, at present, there is a lack of safe and effective ideal drugs for the prevention and treatment of POCD. Melatonin is one of the hormones secreted by the pineal gland of the brain, which has the functions of regulating circadian rhythm, anti-inflammation, anti-oxidation, anti-apoptosis, and so on. Some recent studies have shown that MT can prevent and treat POCD by adjusting circadian rhythm, restoring cholinergic system function, neuroprotection, and so on. This article will introduce POCD, melatonin and the mechanism of melatonin on POCD, respectively, to provide a basis for clinical prevention and treatment of POCD in the elderly.
PubMed: 35356294
DOI: 10.3389/fnagi.2022.782358 -
Pediatric Neurosurgery 2023Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive... (Review)
Review
BACKGROUND
Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive multimodal treatment, the prognosis of many types is guarded, and treatment-related toxicity is significant. Recent advances in molecular diagnostics allowed the discovery of novel entities and inter-tumor subgroups, with opportunities for improved risk-stratification and treatment approaches.
SUMMARY
Medulloblastomas separate into four distinct subgroups with distinct clinicopathologic characteristics, and data from recent clinical trials for newly diagnosed medulloblastoma support subgroup-specific treatment approaches. Atypical teratoid rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and pineoblastoma, as well as other rare embryonal tumors, can be distinguished from histologically similar tumors by virtue of characteristic molecular findings, with DNA methylation analysis providing a strong adjunct in indeterminate cases. Methylation analysis can also allow further subgrouping of ATRT and pineoblastoma. Despite the dire need to improve outcomes for patients with these tumors, their rarity and lack of actionable targets lead to a paucity of clinical trials and novel therapeutics.
KEY MESSAGES
(1) Embryonal tumors can be accurately diagnosed with pediatric-specific sequencing techniques. (2) Medulloblastoma risk stratification and treatment decisions should take into account molecular subgroups. (3) There is a dire need for a novel collaborative clinical trial design to improve outcomes is rare pediatric embryonal tumors.
Topics: Child, Preschool; Humans; Infant; Brain Neoplasms; Central Nervous System Neoplasms; Cerebellar Neoplasms; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Pineal Gland; Pinealoma; Rhabdoid Tumor; Clinical Trials as Topic
PubMed: 37245504
DOI: 10.1159/000531256 -
Frontiers in Neuroinformatics 2021Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are numerous reports on the facilitatory...
Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are numerous reports on the facilitatory role of this area for brain function; hormone secretion and its role in sleep cycle are the major reports. However, reports are rarely available on the direct role of this structure in brain cognition and in information processing. A suggestion for the limited number of such studies is the lack of a standard atlas for the PG; none of the available MRI templates and atlases has provided parcellations for this structure. In this study, we used the three-dimensional (3D) T1-weighted MRI data of 152 healthy young volunteers, and provided a probabilistic map of the PG in the standard Montreal Neurologic Institute (MNI) space. The methods included collecting the data using a 64-channel head coil on a 3-Tesla Prisma MRI Scanner, manual delineation of the PG by two experts, and robust template and atlas construction algorithms. This atlas is freely accessible, and we hope importing this atlas in the well-known neuroimaging software packages would help to identify other probable roles of the PG in brain function. It could also be used to study pineal cysts, for volumetric analyses, and to test any associations between the cognitive abilities of the human and the structure of the PG.
PubMed: 34079447
DOI: 10.3389/fninf.2021.554229 -
Aging Jan 2020We aimed to investigate the association of pineal gland volume with the risk of isolated rapid eye movement (REM) sleep behavior disorder (RBD). We enrolled 245...
We aimed to investigate the association of pineal gland volume with the risk of isolated rapid eye movement (REM) sleep behavior disorder (RBD). We enrolled 245 community-dwelling cognitively normal elderly individuals without major psychiatric or neurological disorders at the baseline evaluation, of whom 146 completed the 2-year follow-up evaluation. We assessed RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as an RBDSQ score of ≥ 5. We manually segmented the pineal gland on 3T T1-weighted brain magnetic resonance imaging and estimated its volume. The smaller the baseline pineal gland volume, the more severe the RBD symptoms at baseline. The individuals with isolated pRBD showed smaller pineal gland volumes than those without isolated pRBD. The larger the baseline pineal gland volume, the lower the risks of prevalent isolated pRBD at the baseline evaluation and incident isolated pRBD at the 2-year follow-up evaluation. Pineal gland volume showed good diagnostic accuracy for prevalent isolated pRBD and predictive accuracy for incident isolated pRBD in the receiver operator characteristic analysis. Our findings suggest that pineal gland volume may be associated with the severity of RBD symptoms and the risk of isolated RBD in cognitively normal elderly individuals.
Topics: Age Factors; Aged; Aged, 80 and over; Aging; Disease Susceptibility; Female; Humans; Incidence; Male; Organ Size; Pineal Gland; Prevalence; REM Sleep Behavior Disorder; ROC Curve; Risk Assessment; Risk Factors
PubMed: 31918412
DOI: 10.18632/aging.102661 -
BMC Genomic Data Feb 2021Long noncoding RNA (lncRNA) has been identified as important regulator in hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, little is known...
BACKGROUND
Long noncoding RNA (lncRNA) has been identified as important regulator in hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, little is known of their expression pattern and potential roles in the pineal gland of sheep. Herein, RNA-Seq was used to detect transcriptome expression pattern in pineal gland between follicular phase (FP) and luteal phase (LP) in FecB (MM) and FecB (ww) STH sheep, respectively, and differentially expressed (DE) lncRNAs and mRNAs associated with reproduction were identified.
RESULTS
Overall, 135 DE lncRNAs and 1360 DE mRNAs in pineal gland between MM and ww sheep were screened. Wherein, 39 DE lncRNAs and 764 DE mRNAs were identified (FP vs LP) in MM sheep, 96 DE lncRNAs and 596 DE mRNAs were identified (FP vs LP) in ww sheep. Moreover, GO and KEGG enrichment analysis indicated that the targets of DE lncRNAs and DE mRNAs were annotated to multiple biological processes such as phototransduction, circadian rhythm, melanogenesis, GSH metabolism and steroid biosynthesis, which directly or indirectly participate in hormone activities to affect sheep reproductive performance. Additionally, co-expression of lncRNAs-mRNAs and the network construction were performed based on correlation analysis, DE lncRNAs can modulate target genes involved in related pathways to affect sheep fecundity. Specifically, XLOC_466330, XLOC_532771, XLOC_028449 targeting RRM2B and GSTK1, XLOC_391199 targeting STMN1, XLOC_503926 targeting RAG2, XLOC_187711 targeting DLG4 were included.
CONCLUSION
All of these differential lncRNAs and mRNAs expression profiles in pineal gland provide a novel resource for elucidating regulatory mechanism underlying STH sheep prolificacy.
Topics: Animals; Female; Follicular Phase; Genotype; Luteal Phase; Pineal Gland; RNA, Long Noncoding; RNA, Messenger; Sheep; Transcriptome
PubMed: 33602139
DOI: 10.1186/s12863-020-00957-w -
The European Journal of Neuroscience Jun 2017Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully...
Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully characterized. Specifically, the expression of connexin36 (Cx36) protein and mRNA has been examined in the pineal, but the identity of cells that produce Cx36 and that form Cx36-containing gap junctions has not been determined. We used immunofluorescence and freeze fracture replica immunogold labelling (FRIL) of Cx36 to investigate the cellular and subcellular localization of Cx36 in the pineal gland of adult mouse and rat. Immunofluorescence labelling of Cx36 was visualized exclusively as puncta or short immunopositive strands that were distributed throughout the pineal, and which were absent in pineal sections from Cx36 null mice. By double immunofluorescence labelling, Cx36 was localized to tryptophan hydroxylase-positive and 5-hydroxytryptamine-positive pinealocyte cell bodies and their large initial processes, including at intersections of those processes and at sites displaying a confluence of processes. Labelling for the cell junction marker zonula occludens-1 (ZO-1) either overlapped or was closely associated with labelling for Cx36. Pinealocytes thus form Cx36-containing gap junctions that also incorporate the scaffolding protein ZO-1. FRIL revealed labelling of Cx36 at ultrastructurally defined gap junctions between pinealocytes, most of which was at gap junctions having reticular, ribbon or string configurations. The results suggest that the endocrine functions of pinealocytes and their secretion of melatonin is supported by their intercellular communication via Cx36-containing gap junctions, which may now be tested by the use of Cx36 null mice.
Topics: Animals; Connexins; Gap Junctions; Male; Mice; Mice, Inbred C57BL; Pineal Gland; Rats; Rats, Sprague-Dawley; Gap Junction delta-2 Protein
PubMed: 28474748
DOI: 10.1111/ejn.13602 -
Acta Neuropathologica May 2021Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal...
Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked the power to integrate molecular and clinical findings. The different proposed molecular group structures also highlighted a need to reach consensus on a robust and relevant classification system. We performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical, and genomic features of patients and samples from these pineal tumor groups were annotated. Four clinically and biologically relevant consensus PB groups were defined: PB-miRNA1 (n = 96), PB-miRNA2 (n = 23), PB-MYC/FOXR2 (n = 34), and PB-RB1 (n = 25). A final molecularly distinct group, designated PPTID (n = 43), comprised histological PPTID and PBs. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual tumor groups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection, and metastatic status varied significantly among tumor groups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 or PB-RB1. Reduced-dose CSI was adequate for patients with average-risk, PB-miRNA1/2 disease. We systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease groups, laying the groundwork for future studies as well as routine use in tumor diagnostic classification and clinical trial stratification.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; DNA Methylation; Female; Genome-Wide Association Study; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pineal Gland; Pinealoma; Transcriptome; Young Adult
PubMed: 33619588
DOI: 10.1007/s00401-021-02284-5 -
International Journal of Surgery... Dec 2023The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions...
BACKGROUND
The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions with high image quality and an ergonomic system for pineal region tumor operations. In this study, the authors describe the exoscopic approach used to facilitate the surgical resection of pineal region tumors and relieve hydrocephalus.
MATERIALS AND METHODS
In this retrospective cohort study, we consecutively reviewed the clinical and radiological data of 25 patients with pineal region lesions who underwent three-dimensional exoscopic tumor resection at a single center.
RESULTS
The patient cohort consisted of 16 males and 9 females, with an average age of 34.6 years (range, 6-62 years; 8 cases aged ≤18). Pathological examination confirmed eight pineal gland tumors, four gliomas, nine germ cell neoplasms, two ependymomas, and two metastatic tumors. Preoperative hydrocephalus was present in 23 patients. Prior to tumor resection, external ventricular drainage (EVD) with Ommaya reservoir implantation was performed in 17 patients. Two patients received preoperative endoscopic third ventriculostomy (ETV), and five patients received a ventriculoperitoneal (VP) shunt, including one who received both procedures. Gross total resection was achieved in 19 patients (76%) in the 'head-up' park bench position using the exoscope. Eight patients (31.6%) with third ventricle invasion received subtotal resection, mainly in glioma cases, which was higher than those without invasion (0%), but not statistically significant ( P =0.278, Fisher's exact test). No new neurological dysfunction was observed after surgery. Two patients (8%) developed intracranial and pulmonary infections, and two patients (8%) suffered from pneumothorax. Hydrocephalus was significantly relieved in all patients postoperatively, and four patients with relapse hydrocephalus were cured during the long-term follow-up. Postoperative adjuvant management was recommended for indicated patients, and a mean follow-up of 24.8±14.3 months showed a satisfied outcome.
CONCLUSIONS
The exoscope is a useful tool for pineal region tumor resection and hydrocephalus relief, particularly with posterior third ventricle invasion, as total resection could be achieved without obvious complication. The special superiority of the exoscope for the indicated pineal region tumors should be highlighted.
Topics: Male; Female; Humans; Adult; Pinealoma; Retrospective Studies; Treatment Outcome; Neoplasm Recurrence, Local; Pineal Gland; Glioma; Ventriculostomy; Third Ventricle; Hydrocephalus; Brain Neoplasms
PubMed: 37755386
DOI: 10.1097/JS9.0000000000000707 -
International Journal of Molecular... Jul 2022The zebrafish has become an excellent model for the study of human diseases because it offers many advantages over other vertebrate animal models. The pineal gland, as... (Review)
Review
The zebrafish has become an excellent model for the study of human diseases because it offers many advantages over other vertebrate animal models. The pineal gland, as well as the biological clock and circadian rhythms, are highly conserved in zebrafish, and melatonin is produced in the pineal gland and in most organs and tissues of the body. Zebrafish have several copies of the clock genes and of and genes, the latter involved in melatonin synthesis. As in mammals, melatonin can act through its membrane receptors, as with zebrafish, and through mechanisms that are independent of receptors. Pineal melatonin regulates peripheral clocks and the circadian rhythms of the body, such as the sleep/wake rhythm, among others. Extrapineal melatonin functions include antioxidant activity, inducing the endogenous antioxidants enzymes, scavenging activity, removing free radicals, anti-inflammatory activity through the regulation of the NF-κB/NLRP3 inflammasome pathway, and a homeostatic role in mitochondria. In this review, we introduce the utility of zebrafish to analyze the mechanisms of action of melatonin. The data here presented showed that the zebrafish is a useful model to study human diseases and that melatonin exerts beneficial effects on many pathophysiological processes involved in these diseases.
Topics: Animals; Antioxidants; Biomedical Research; Circadian Rhythm; Humans; Mammals; Melatonin; Pineal Gland; Zebrafish
PubMed: 35806441
DOI: 10.3390/ijms23137438