Exploration of the white matter bundles connected to the pineal gland: A DTI study.

PURPOSE: 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 reports on the role of this area for brain function by hormone secretion, as well as few reports on its role in brain cognition. However, little knowledge is available on the PG, and in particular on the structural connectivity of this region with the other brain structures. METHODS: Using diffusion-weighted images collected by a 3T MRI scanner, and using a sample of 61 (29 F) mentally and physically healthy young individuals in the age range of 20-30 years old, we tried to extract the white matter bundles connected to the PG. Based on prior knowledge, seven target bundles were suggested to be between the PG body and the PG roots, Pons, Periventricular region, thalamus, caudate, lentiform, suprachiasmatic nuclei, and the supercervical ganglia. RESULTS: Nearly all the target bundles were successfully extracted, with the exception of the lentiform. Rate of identification of the tracts was different, with the bundle between the PG body and roots having the highest identification rate (97%); then it was with the Pons (70%), Periventricular region (57%), SCN (55%), left thalamus (52%), right thalamus (47%), left caudate (27%) and right caudate (22%). CONCLUSION: This study is an attempt to expand our knowledge on the neuroanatomy of the PG, which might help for identifying further roles for it in brain functionality, and also be a help for the treatment of some disorders in the future.

A morphological study of human pineal gland in post-mortem cases.

The current study was conducted in the Department of Anatomy, Osmania Medical College, Koti, Hyderabad over a period of 1year. A total of 30 human pineal glands (16-males,11-females,3 excluded for post-mortem autolysis) from those bodies between the age groups of 1-80years were collected during the post-mortem study at the Mortuary of Osmania General Hospital, Koti, Hyderabad and were included in the study. Morphological parameters like weight and transverse diameter at the maximum width of the pineal glands were measured and then the pineal glands were processed for light microscopy. 4-5micron thick sections were cut and stained with H&E and Masson Trichrome for highlighting the connective tissue pattern of the pineal gland. Under light microscope, the capsular delineation, pattern of septation and lobulation, calcification, intracellular brown pigment, intraparenchymal inflammatory cells, fibrosis, gliosis and cystic changes in the pineal glands were observed in relation to age and gender.

Assessment of the normal pediatric pineal gland - MR findings of a single centre; A retrospective study.

OBJECTIVE: To analyse the size and morphology of the normal pineal gland in the paediatric age group using magnetic resonance imaging. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients aged <18 years who had magnetic resonance imaging done between 2007 and 2017. Pineal size was estimated measuring its largest anteroposterior and supero-inferior diameters on sagittal T2-weighted sequences on any slice with maximal diameter. The width of pineal gland was measured on axial or coronal T2 sequences. The volume, morphology and enhancement patterns of the gland were also assessed. Data was analysed using SPSS 21. RESULTS: Of the 200 patients, 116(58%) were males and 84(42%) were females. The overall mean age was 7.8±5.5 years. The mean anteroposterior dimension was 4.85±1.46mm, height 3.31±0.95mm, width 4.16±1.19, and volume 39.54±38.12 mm3. Mean size of cyst was 2.77±1.4mm (range: 1.2-7.5mm). No significant differences in the pattern of enhancement were found in different age groups (p>0.05). CONCLUSIONS: Comprehensive knowledge of the size of the typical pineal organ is useful for radiologists in the identification of pineal gland anomalies and the exclusion of neoplastic lesions.

Revisiting the pineal gland: a review of calcification, masses, precocious puberty, and melatonin functions.

Introduction: The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement and curiosity. Methods: We review present an up-to-date review including the anatomy, embryology, and physiology of the pineal gland and its ability to secrete hormones including melatonin, pathophysiology of pineal gland tumors, cysts, and calcifications, their clinical presentation including their association with parkinsonism and precocious puberty, and various treatment approaches. Results: Exploring the biochemistry of melatonin, various calcification morphologies, and pineal tumors may uncover a wider role and the exhaustive case study consolidation allows clinicians to carefully review the literature and aid their treatment approaches. Conclusion: It is imperative that clinicians and diagnosticians are able to distinguish manifestations of an overlooked gland.

The origins of the circumventricular organs.

The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They mediate the communication between the brain and the periphery by performing sensory and secretory roles, facilitated by increased vascularisation and the absence of a blood-brain barrier. Surprisingly little is known about the origins of the CVOs (both developmental and evolutionary), but their functional and organisational similarities raise the question of the extent of their relationship. Here, I review our current knowledge of the embryonic development of the seven major CVOs (area postrema, median eminence, neurohypophysis, organum vasculosum of the lamina terminalis, pineal organ, subcommissural organ, subfornical organ) in embryos of different vertebrate species. Although there are conspicuous similarities between subsets of CVOs, no unifying feature characteristic of their development has been identified. Cross-species comparisons suggest that CVOs also display a high degree of evolutionary flexibility. Thus, the term 'CVO' is merely a functional definition, and features shared by multiple CVOs may be the result of homoplasy rather than ontogenetic or phylogenetic relationships.

Sex Difference in the Morphology of Pineal Gland in Adults Based on Brain Magnetic Resonance Imaging.

PURPOSE: We aimed to figure out the anatomical features of pineal gland region on magnetic resonance imaging (MRI) and to explore the sex difference in pineal gland-related parameters with increasing age. METHODS: We measured the pineal gland on MRI images from 198 healthy adults (96 males and 102 females). Included subjects were divided into 4 age groups. After 3-dimensional reconstruction, the anatomic features of pineal gland and its distances to superior colliculus and splenium of corpus callosum were analyzed in each group. The prevalence of cystic pineal gland was calculated. Moreover, we calculated the volume of pineal gland (PGV) and explored the differences of PGV in males and females across different age groups. Linear regression analysis was performed to detect the relationship between age and pineal gland-related parameters. RESULTS: In 198 subjects, the mean length, width, and height of pineal gland were 7.58 ±â€Š0.45 mm, 4.92 ±â€Š0.40 mm, and 2.90 ±â€Š0.20 mm. The distances between pineal gland and superior colliculus as well as splenium of corpus callosum were 3.96 ±â€Š0.92 mm and 4.3 ±â€Š1.89 mm, respectively. The PGV was 54.1 ±â€Š7.02 mm. Significant sex differences were found in pineal gland length (P < 0.001), cranial cavity diameter (P < 0.001), pineal gland index (P < 0.001) and PGV values (P = 0.02). The prevalence of cystic pineal gland was 36.4% in total subjects, 41.7% in males and 32.4% in females. No linear relationship was found between age and pineal gland parameters. CONCLUSION: We measured the pineal gland morphology based on MRI images. Significant influences on pineal gland parameters were found in subjects with different sex, whereas no effect was observed from age.

Evidence of Pineal Gland Calcification on CBCT is Not Insignificant: What Else You Might Discover about Your Patient.

The use of CBCT technology in the dental office is increasing rapidly. These scans provide information on anatomy not previously evaluated with traditional 2D films. One structure often mentioned in a CBCT radiology report is the pineal gland. The pineal gland will show evidence of calcification, but this calcification is often dismissed as a normal aging process. This review of the function and influence of the pineal gland may influence the doctor to complete further evaluation of the patient.

Physiological implications of the abnormal absence of the parietal foramen in a late Permian cynodont (Therapsida).

The third eye (pineal eye), an organ responsible for regulating exposure to sunlight in extant ectotherms, is located in an opening on the dorsal surface of the skull, the parietal foramen. The parietal foramen is absent in extant mammals but often observed in basal therapsids, the stem-group to true mammals. Here, we report the absence of the parietal foramen in a specimen of Cynosaurus suppostus, a Late Permian cynodont from South Africa (SA). Comparison with Procynosuchus delaharpeae, a contemporaneous non-mammalian cynodont from SA, demonstrates that the absence of this foramen is an abnormal condition for such a basal species. Because seasonality was marked during the Late Permian in SA, it is proposed that the third eye was functionally redundant in Cynosaurus, possibly due to the acquisition of better thermoregulation or the evolution of specialized cells in the lateral eyes to compensate for the role of the third eye.

The Parapineal Is Incorporated into the Habenula during Ontogenesis in the Medaka Fish.

The parapineal is present in many teleost families, while it is absent in several others. To find out why the parapineal is absent at adult stages in the latter families, the development of the epithalamus was examined in the medaka fish (Oryzias latipes). For this purpose, a green fluorescent protein-transgenic medaka line, in which the pineal complex (pineal and parapineal) is visible fluorescently, was used. We found that a distinct parapineal was present in the roof plate at early developmental stages. Subsequently, however, the parapineal and the associated roof plate began to be incorporated into the habenula between embryonic stages 28 and 29. Between embryonic stages 29 and 30, the entire parapineal was incorporated into the habenula. That is, the parapineal became a small caudomedial region (termed the 'parapineal domain') within the left habenula in the majority of embryos, resulting in the left-sided asymmetry of the epithalamus. Thereby the left habenula became larger and more complex than its right counterpart. In the minority of embryos, the parapineal was incorporated into the right habenula or into the habenulae on both sides. In the majority of embryos, the parapineal domain projected a fiber bundle to a subnucleus (termed the 'rostromedial subnucleus') in the left habenula. The rostromedial subnucleus sent axons, through the left fasciculus retroflexus, to the rostral region of the left half of the interpeduncular nucleus. We further found that the ratio of the left-sided phenotype was temperature dependent and decreased in embryos raised at a high temperature. The present study is the first demonstration that the supposed lack of a distinct parapineal in adult teleost fishes is due to ontogenetic incorporation into the habenula.

Effects of Melatonin on Morphological and Functional Parameters of the Pineal Gland and Organs of Immune System in Rats During Natural Light Cycle and Constant Illumination.

We studied the response of the pineal gland and organs of the immune system to melatonin treatment in Wistar rats kept under conditions of abnormal illumination regimen. The animals were kept under natural light regimen or continuous illumination for 14 days and then received daily injections of melatonin (once a day in the evening) for 7 days. Administration of melatonin to rats kept at natural light cycle was followed by a decrease in percent ratio of CD4+8+ splenocytes and CD4-8+ thymocytes. In 24-h light with the following melatonin injections were accompanied by an increase in percent rate and absolute amount of CD4+8+ cells in the spleen, and a decrease in percent rate of CD11b/c and CD4-8+ splenocytes. In the thymus amount of CD4-8+ cells increased, and absolute number of CD4+25+ cells reduced. Melatonin significantly decreased lipofuscin concentration in the pineal gland during continuous light. Direction and intensity of effects of melatonin on parameters of cell immunity and state of the pineal gland were different under normal and continuous light conditions. It should be taken into account during using of this hormone for correction of immune and endocrine impairments developing during change in light/dark rhythm.

Morphology and function: MR pineal volume and melatonin level in human saliva are correlated.

PURPOSE: To investigate the relation between circadian saliva melatonin levels and pineal volume as determined by MRI. Plasma melatonin levels follow a circadian rhythm with a high interindividual variability. MATERIALS AND METHODS: In 103 healthy individuals saliva melatonin levels were determined at four time points within 24 h and MRI was performed once (3.0 Tesla, including three-dimensional T2 turbo spin echo [3D-T2-TSE], susceptibility-weighted imaging [SWI]). Pineal volume as well as cyst volume were assessed from multiplanar reconstructed 3D-T2-TSE images. Pineal calcification volume tissue was determined on SWI. To correct for hormonal inactive pineal tissue, cystic and calcified areas were excluded. Sleep quality was assessed with the Landeck Inventory for sleep quality disturbance. RESULTS: Solid and uncalcified pineal volume correlated to melatonin maximum (r = 0.28; P < 0.05) and area under the curve (r = 0.29; P < 0.05). Of interest, solid and uncalcified pineal volume correlated negatively with the sleep rhythm disturbances subscore (r = -0.17; P < 0.05) despite a very homogenous population. CONCLUSION: Uncalcified solid pineal tissue measured by 3D-T2-TSE and SWI is related to human saliva melatonin levels. The analysis of the sleep quality and pineal volume suggests a linkage between better sleep quality and hormonal active pineal tissue.

Pineal gland volume in primary insomnia and healthy controls: a magnetic resonance imaging study.

Little is known about the relation between pineal volume and insomnia. Melatonin promotes sleep processes and, administered as a drug, it is suitable to improve primary and secondary sleep disorders in humans. Recent magnetic resonance imaging studies suggest that human plasma and saliva melatonin levels are partially determined by the pineal gland volume. This study compares the pineal volume in a group of patients with primary insomnia to a group of healthy people without sleep disturbance. Pineal gland volume (PGV) was measured on the basis of high-resolution 3 Tesla MRI (T1-magnetization prepared rapid gradient echo) in 23 patients and 27 controls, matched for age, gender and educational status. Volume measurements were performed conventionally by manual delineation of the pineal borders in multi-planar reconstructed images. Pineal gland volume was significantly smaller (P < 0.001) in patients (48.9 ± 26.6 mm(3) ) than in controls (79 ± 30.2 mm(3) ). In patients PGV correlated negatively with age (r = -0.532; P = 0.026). Adjusting for the effect of age, PGV and rapid eye movement (REM) latency showed a significant positive correlation (rS  = 0.711, P < 0.001) in patients. Pineal volume appears to be reduced in patients with primary insomnia compared to healthy controls. Further studies are needed to clarify whether low pineal volume is the basis or the consequence of functional sleep changes to elucidate the molecular pathology for the pineal volume loss in primary insomnia.

The pineal complex in the cichlid Cichlasoma dimerus: effect of different photoperiods on its cell morphology.

This research describes the pineal complex histology in juvenile and adult Cichlasoma dimerus, and the effect of different photoperiods on its cell morphology. In both juveniles and adults, the pineal complex of C. dimerus has three components: the pineal organ, consisting of a pineal vesicle (PV) and a pineal stalk, the parapineal organ and the dorsal sac. Although a strong morphological resemblance exists between the two stages, different synthesis patterns of cone and rod opsins were detected in the two life stages. An effect of the photoperiod length was observed on putative pinealocytes' activity from the PV, measured indirectly through nuclear area morphometry. Individuals exposed to a natural photoperiod (14L:10D) had smaller nuclear areas (mean ± s.e. = 13·82 ± 1·52 µm(2) ) than those exposed to a short photoperiod (8:16) (21·45 ± 2·67 µm(2) ; P < 0·001). Eventually, the nuclear area of pinealocytes could be used as a putative indicator of melatonin synthesis in fishes where it is difficult to obtain plasma samples, e.g. due to its small size or age. This work constitutes one of the few comparative descriptions of the pineal complex of juvenile and adult teleost and suggests potential approaches for the study of melatonin synthesis in fish larvae or small adult fishes.

Comparison of three methods for the estimation of pineal gland volume using magnetic resonance imaging.

Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm(3), respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation.

Crx broadly modulates the pineal transcriptome.

Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. In this study, the influence of Crx on the mammalian pineal gland was studied by light and electron microscopy and by use of microarray and qRTPCR technology, thereby extending previous studies on selected genes (Furukawa et al. 1999). Deletion of Crx was not found to alter pineal morphology, but was found to broadly modulate the mouse pineal transcriptome, characterized by a>2-fold down-regulation of 543 genes and a>2-fold up-regulation of 745 genes (p<0.05). Of these, one of the most highly up-regulated (18-fold) was Hoxc4, a member of the Hox gene family, members of which are known to control gene expression cascades. During a 24-h period, a set of 51 genes exhibited differential day/night expression in pineal glands of wild-type animals; only eight of these were also day/night expressed in the Crx⁻/⁻ pineal gland. However, in the Crx⁻/⁻ pineal gland 41 genes exhibited differential night/day expression that was not seen in wild-type animals. These findings indicate that Crx broadly modulates the pineal transcriptome and also influences differential night/day gene expression in this tissue. Some effects of Crx deletion on the pineal transcriptome might be mediated by Hoxc4 up-regulation.

Global daily dynamics of the pineal transcriptome.

Transcriptome profiling of the pineal gland has revealed night/day differences in the expression of a major fraction of the genes active in this tissue, with two-thirds of these being nocturnal increases. A set of over 600 transcripts exhibit two-fold to >100-fold daily differences in abundance. These changes appear to be primarily attributable to adrenergic-cyclic-AMP-dependent mechanisms, which are controlled via a neural pathway that includes the suprachiasmatic nucleus, the master circadian oscillator. In addition to melatonin synthesis, night/day differences in gene expression impact genes associated with several specialized functions, including the immune/inflammation response, photo-transduction, and thyroid hormone/retinoic acid biology. The following nonspecialized cellular features are also affected: adhesion, cell cycle/cell death, cytoskeleton, DNA modification, endothelium, growth, RNA modification, small molecule biology, transcription factors, vesicle biology, signaling involving Ca(2+), cyclic nucleotides, phospholipids, mitogen-activated protein kinases, the Wnt signaling pathway, and protein phosphorylation.

A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge.

Classification of the venous architecture of the pineal gland by 7T MRI.

Magnetic resonance imaging (MRI) at 7.0 Tesla (7T) can show many details of anatomical structures with unprecedented resolution and contrast. In this report, we describe for the first time the unexpected wide variation in pineal gland structure, as visualized by MR images obtained with 7T in a group of healthy young volunteers. A total of 34 volunteers (22 men and 12 women) were enrolled in the study. Their 7T MR images revealed such wide variations in pineal gland shape that it led us to attempt to classify the patterns seen in these pineal glands. Indeed, they were successfully correlated with a previous human cadaver study of venous structures by Tamaki et al., who classified the venous structures of the pineal gland into three categories. This is the first human in vivo pineal vein imaging study using 7T MRI. Pineal venous imaging may permit the early diagnosis of a pineal tumor.