Neuroendocrine effects of light

NASA Astrophysics Data System (ADS)

Reiter, Russel J.

1991-09-01

The light/dark cycle to which animals, and possibly humans, are exposed has a major impact on their physiology. The mechanisms whereby specific tissues respond to the light/dark cycle involve the pineal hormone melatonin. The pineal gland, an end organ of the visual system in mammals, produces the hormone melatonin only at night, at which time it is released into the blood. The duration of elevated nightly melatonin provides every tissue with information about the time of day and time of year (in animals that are kept under naturally changing photoperiods). Besides its release in a circadian mode, melatonin is also discharged in a pulsatile manner; the physiological significance, if any, of pulsatile melatonin release remains unknown. The exposure of animals including man to light at night rapidly depresses pineal melatonin synthesis and, therefore, blood melatonin levels drop precipitously. The brightness of light at night required to depress melatonin production is highly species specific. In general, the pineal gland of nocturnally active mammals, which possess rod-dominated retinas, is more sensitive to inhibition by light than is the pineal gland of diurnally active animals (with cone-dominated retinas). Because of the ability of the light/dark cycle to determine melatonin production, the photoperiod is capable of influencing the function of a variety of endocrine and non-endocrine organs. Indeed, melatonin is a ubiquitously acting pineal hormone with its effects on the neuroendocrine system having been most thoroughly investigated. Thus, in nonhuman photoperiodic mammals melatonin regulates seasonal reproduction; in humans also, the indole has been implicated in the control of reproductive physiology.

[Aging of the pineal gland].

PubMed

Khavinson, V Kh; Golubev, A G

2002-01-01

The age-related changes in the pineal gland are functional rather than organic, which makes their correction or prevention more tenable. The amelioration or inhibition of some age-related impairments of the pineal gland were observed with dietary restriction and the use of S-adenosylmethionine or MAO-A inhibitors. A threefold increase in nocturnal melatonin peaks occurs in old rhesus monkeys treated with a synthetic peptide Ala-Glu-Asp-Gly (Epithalon) designed basing on the amino acid content of a pineal peptide extract Epithalamin. Other effects of Epithalon markedly overlap with melatonin effects. Besides life extension in mice and fruit flies, Epithalon effects include the postponing vision loss in Campbell rats with hereditary pigmental dystrophy. A uniting aspect of such a range of activities might be the participation of transcription factors, since they are often highly conservative in evolution and, on the other hand, may be strictly tissue-specific. The targets of Epithalon may include transfactors that in mammals are specific for the pineal gland and retina and exhibit impaired functions in the aged pineal gland.

Non-invasive evaluation of the effects of opening & closing of eyes, and of exposure to a minute light beam, as well as to electrical or magnetic field on the melatonin, serotonin, & other neuro-transmitters of human pineal gland representation areas & the heart.

PubMed

Omura, Y; Losco, B M; Takeshige, C

1993-01-01

Using the Bi-Digital O-Ring Test electromagnetic resonance phenomena between 2 identical substances, first the pineal gland representational (rep.) areas were localized on the 5 different locations on the surface of the head using microscope slides of the pineal gland or Melatonin (while the eyes are closed) as a reference control substance. The 3 pineal rep. areas along the mid-line of the head always showed two lobes connected as a "Dumbbell" shape, with one round or oval area at each side of the mid-line. From each side of the head, anterior and superior to the ear, it appeared in a shape resembling the side view of a pineal gland. When both eyes were open, Melatonin, Norepinephrine (NE), and Acetylcholine (ACh) markedly decreased, while Serotonin, Dopamine, and GABA increased significantly in the outer part of the pineal gland rep. areas. When both eyes were closed, Melatonin, NE and ACh increased markedly, with marked decrease in Serotonin, Dopamine and GABA in the outer part of the pineal gland rep. areas. However, in the inner core of the pineal gland rep. area, an opposite response was found. Thus, the pineal gland has 2 main lobes, and functionally each lobe seems to have two concentric areas with an inverse relationship, i.e., a "Functional Cortex" area and a "Functional Core" area. The biochemical changes between the cortex and the core are in an inverse relationship. Melatonin was also found in the S-A node & right side of normal heart when the eyes were closed. When the eyes were open, Melatonin was found in the left side of the heart, as well as the salivary glands, stomach, colon, etc. While both eyes were closed, when a weak light beam was exposed at different parts of the body, such as any part of the upper and lower extremities, Melatonin, NE, and ACh decreased, with an increase in Serotonin, GABA and Dopamine only in the functional cortices of the pineal gland lobes on the same side of the body. Even when both eyes were open, if a very weak narrow beam of light was exposed on any part of the body, Melatonin, NE and ACh decreased, while Serotonin, Dopamine and GABA increased compared with pre-exposure level in only the functional cortices of the pineal gland lobes in the same side of the light exposure, and the opposite effect was also observed in the functional core of the light exposed side only.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulating effect of epithalone on gastric endocrine cells in pinealectomized rats.

PubMed

Khavinson, V K; Popuchiev, V V; Kvetnoii, I M; Yuzhakov, V V; Kotlova, L N

2000-12-01

Endocrine cells in the stomach of pinealectomized rats after injection of epithalone (pineal gland peptide) were studied by immunohistochemical tests, morphometry, and image analysis microscopic images. A functional relationship was found between the pineal gland and stomach, which is regulated by peptides produced by the pineal gland.

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

PubMed

Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Ozçelik, Ozlem; Yıldırım, Birdal; Turgut, Mehmet

2012-01-01

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.

Comparison of Three Methods for the Estimation of Pineal Gland Volume Using Magnetic Resonance Imaging

PubMed Central

Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Özçelik, Özlem; Yıldırım, Birdal; Turgut, Mehmet

2012-01-01

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 mm3, 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. PMID:22619577

EXTIRPATION OF THE PINEAL BODY

PubMed Central

Dandy, Walter E.

1915-01-01

1. Following the removal of the pineal I have observed no sexual precocity or indolence, no adiposity or emaciation, no somatic or mental precocity or retardation. 2. Our experiments seem to have yielded nothing to sustain the view that the pineal gland has an active endocrine function of importance either in the very young or adult dogs. 3. The pineal is apparently not essential to life and seems to have no influence upon the animal's well being. PMID:19867913

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland.

PubMed

Tan, Dun Xian; Xu, Bing; Zhou, Xinjia; Reiter, Russel J

2018-01-31

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

COSMOS 2044. Experiment K-7-19. Pineal physiology in microgravity: Relation to rat gonadal function

NASA Technical Reports Server (NTRS)

Holley, D.; Soliman, M. R. I.; Krasnov, I.; Asadi, H.

1989-01-01

It is now known that the pineal organ can interact with many endocrine and nonendocrine tissues in a regulatory fashion. Given its key role in the regulation of melatonin synthesis, its high concentration, and that its levels may persist longer than the more rapidly changing melatonin, it was felt that serotonin might give a more accurate assessment of the effects of microgravity on pineal function following recovery of animals from flight. Five-hydroxyindole acetic acid (5-HIAA), a major metabolite of serotonin metabolism, was also measured. One of the most interesting concomitants to spaceflight and exposure to microgravity has been the disturbing alteration in calcium metabolism and resulting skeletal effects. Given the link between exposure to microgravity and perturbation of calcium metabolism and the fact that the pineal is apparently one of the only soft tissues to calcify, pineal calcium content was examined following spaceflight.

The role of pineal gland in breast cancer development.

PubMed

Anisimov, Vladimir N

2003-06-01

The role of the modulation of the pineal gland function in development of breast cancer is discussed in this review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits mammary carcinogenesis in pinealectomized rats, in animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen. Pineal peptide preparation Epithalamin and synthetic tetrapeptide Epitalon (Ala-Glu-Asp-Gly) are potent inhibitors of mammary carcinogenesis in rodents and might be useful in the prevention of breast cancer in women at risk.

[Effect of pineal peptides on neuroendocrine system after pinealectomy].

PubMed

Khavinson, V Kh; Kvetnoĭ, I M; Popuchiev, V V; Iuzhakov, V V; Kotlova, L N

2001-01-01

Removal of the pineal gland leads to structural and functional rearrangement of gastric endocrine cells and thyroid C-cells in albino rats, as was shown by immunohistological methods and morphometry. Injection of pineal peptides epithalone and epithalamine eliminated these changes. Biological activity of epithalone is believed to be higher than that of epithalamine.

Rhythmic control of endocannabinoids in the rat pineal gland.

PubMed

Koch, Marco; Ferreirós, Nerea; Geisslinger, Gerd; Dehghani, Faramarz; Korf, Horst-Werner

2015-01-01

Endocannabinoids modulate neuroendocrine networks by directly targeting cannabinoid receptors. The time-hormone melatonin synchronizes these networks with external light condition and guarantees time-sensitive and ecologically well-adapted behaviors. Here, the endocannabinoid arachidonoyl ethanolamide (AEA) showed rhythmic changes in rat pineal glands with higher levels during the light-period and reduced amounts at the onset of darkness. Norepinephrine, the essential stimulus for nocturnal melatonin biosynthesis, acutely down-regulated AEA and other endocannabinoids in cultured pineal glands. These temporal dynamics suggest that AEA exerts time-dependent autocrine and/or paracrine functions within the pineal. Moreover, endocananbinoids may be released from the pineal into the CSF or blood stream.

Descartes and the pineal gland in animals: a frequent misinterpretation.

PubMed

Finger, S

1995-01-01

René Descartes presented a number of reasons for his choice of the pineal gland as a logical place for the soul to interact with the physical machinery of the body. It is often stated that one of his reasons was that he believed animals do not have pineal glands, whereas humans alone possess a soul and this small structure. This is a misinterpretation of Descartes. The philosopher knew that barnyard and other animals possess pineal glands, having seen this with his own eyes. His point was that the pineal is unique in humans only because of a special function - acting as the seat for the rational soul.

Habenular commissure formation in zebrafish is regulated by the pineal gland-specific gene unc119c.

PubMed

Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L; Gonzales, John; Burgess, Harold; Dawid, Igor B

2013-09-01

The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and, therefore, is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. Copyright © 2013 Wiley Periodicals, Inc.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

PubMed

Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-03-15

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

Habenular commissure formation in zebrafish is regulated by the pineal gland specific gene unc119c

PubMed Central

Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L.; Gonzales, John; Burgess, Harold; Dawid, Igor B.

2013-01-01

Background The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and therefore is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Results Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. Conclusions We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. PMID:23749482

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

PubMed Central

Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-01-01

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

Factors other than light affecting the pineal gland: hypophysectomy, testosterone, dihydrotestosterone, estradiol, cryptorchidism, and stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urry, R.L.; Dougherty, K.A.; Frehn, J.L.

The article reviews those factors other than light that affect the activity of the pineal gland. Both testosterone and dihydroterosterone were shown to have tissue-specific inhibitory effects on pineal MAO activity concomitant with an increased activity of the gland. The effect also was tissue-specific. Bilateral and unilateral experimental cryptorchidism also decreased pineal MAO activity 3 to 4 weeks after surgery. Acute stresses appear to increase adrenal catecholamine output (epinephrine and norepinephrine) as well as to stimulate local adrenergic pathways, while chronic stress, such as starvation, appears to act through the adrenal corticosteroids by decreasing pineal MAO activity thereby indirectly increasingmore » melatonin synthesis. Thus, both components of the adrenal gland appear to act in concert to increase effectively melatonin synthesis by the pineal function----the latter specifically inhibits HIOMT activity. These observations indicate that many factors other than light affect pineal morphology and melatonin synthesis. The pineal appears to be a true neuroendocrine organ that is affected by hypophysectomy and is responsive to feedback and control from other organs within the mammalian organism. (auth)« less

Neuropeptide Y in the adult and fetal human pineal gland.

PubMed

Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

Neuropeptide Y in the Adult and Fetal Human Pineal Gland

PubMed Central

Møller, Morten; Phansuwan-Pujito, Pansiri

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally. PMID:24757681

[Peptide correction of age-related pineal disturbances in monkeys].

PubMed

Goncharova, N D; Vengerin, A A; Shmaliĭ, A V; Khavinson, V Kh

2003-01-01

Investigation of the age-related changes of the pineal gland function and possible ways for their overcoming on nonhuman monkey model was the purpose of this study. Hormonal function of the pineal gland was studied in 38 Macaca mulatta females of two age groups: 6-8 years old, n = 18 and 20-26 years old, n = 20. Pineal function was studied in basal conditions and after administration of pineal peptide preparations--epithalamin and epitalon, both developed in the St. Petersburg Institute of Bioregulation and Gerontology (Russia). It has been revealed that plasma melatonin concentration in monkeys has well expressed high amplitude diurnal rhythm. Minimum is manifested at 4 p.m. and maximum--at 10 p.m.-3 a.m. In aging the mean diurnal melatonin concentration decreases by 1.5-2 times as well as in different points of the day: 9 p.m., 10 p.m., 3 a.m. and 4 a.m. Administration of pineal peptides--epithalamin (at the dose 5 mg/animal/day intramuscularly during 10 consecutive days) or epitalon (at the dose 10 micrograms/animal/day intramuscularly during 7-10 consecutive days) induced significant increase in the night plasma melatonin in old monkeys, but the treatment did not change the melatonin level in young monkeys. Taking into consideration that melatonin is very important for regulation of the diurnal rhythm of functioning of some organs and systems it should be suggested that applying epithalamin and epitalon are perspective in the correction of age-related hormonal imbalance and age pathology.

Rax: Developmental and Daily Expression Patterns in the Rat Pineal Gland and Retina

PubMed Central

Rohde, Kristian; Klein, David C.; Møller, Morten; Rath, Martin F.

2011-01-01

Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes to phenotype maintenance in the mature retina and pineal gland and may facilitate 24-h changes in the pineal transcriptome. PMID:21749377

Ophthalmological outcome after resection of tumors based on the pineal gland.

PubMed

Hart, Michael G; Sarkies, Nicholas J; Santarius, Thomas; Kirollos, Ramez W

2013-08-01

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland. Review of a retrospective case series was performed and included consecutive patients who underwent surgery performed by a consultant neurosurgeon between 2002 and 2011. Only tumors specifically based on the pineal gland were included; tumors encroaching on the pineal gland from other regions were excluded. All patients with visual signs and/or symptoms were reviewed by a specialist consultant neuroophthalmologist to accurately characterize the nature of their deficits. Visual disturbance was defined as visual symptoms caused by a disturbance of ocular motility. A total of 20 patients underwent resection of pineal gland tumors. Complete resection was obtained in 85%, and there were no perioperative deaths. Visual disturbance was present in 35% at presentation; of those who had normal ocular motility preoperatively 82% had normal motility postoperatively. In total, 55% of patients had residual visual disturbance postoperatively. Although upward gaze tended to improve, significant functional deficits remained, particularly with regard to complex convergence and accommodation dysfunction. Prisms were used in 25% but were only ever partially effective. Visual outcome was only related to preoperative visual status and tumor volume (multivariate analysis). Long-term visual morbidity after pineal gland tumor resection is common and leads to significant functional impairment. Improvement in deficits rarely occurs spontaneously, and prisms only have limited effectiveness, probably due to the dynamic nature of supranuclear ocular movement coordination.

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

PubMed

Fore, Stacy

2016-01-01

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.

Pineal physiology in microgravity - Relation to rat gonadal function aboard Cosmos 1887

NASA Technical Reports Server (NTRS)

Holley, Daniel C.; Markley, Carol L.; Soliman, Magdi R. I.; Kaddis, Farida; Krasnov, Igor'

1991-01-01

Results are reported from an analysis of pineal glands obtained for five male rats flown aboard an orbiting satellite for their melatonin, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIA), and calcium content. Plasma 5-HT and 5-HIAA were measured. These parameters were compared to indicators of gonadal function: plasma testosterone concentration and spermatogonia development. Plasma melotonin was found to be low at the time of euthanasia and was not different among the experimental groups. Pineal calcium of flight animals was not different from ground controls. Pineal 5-HT and 5-HIAA in the flight group were significantly higher than those in ground controls. These findings suggest a possible increase in pineal 5-HT turnover in flight animals which may result in increased melatonin secretion. It is argued that the alteration of pinal 5-HT turnover and its expected effects on melatonin secretion may partially explain the lower plasma testosterone levels and 4-11 percent fewer spermatogonia cells observed in flight animals.

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

PubMed

Liebrich, Luisa-Sophie; Schredl, Michael; Findeisen, Peter; Groden, Christoph; Bumb, Jan Malte; Nölte, Ingo S

2014-10-01

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. 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. 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. 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. © 2013 Wiley Periodicals, Inc.

Electrical stimulation of the hypothalamic nucleus paraventricularis mimics the effects of light on pineal melatonin synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olcese, J.; Reuss, S.; Steinlechner, S.

In an attempt to clarify further the role of the hypothalamic paraventricular nuclei (PVN) in the control of pineal function, the effects of 2 min electrical stimulation of these nuclei were investigated in acutely blinded, adult, male Sprague-Dawley rats. Pineal serotonin-N-acetyltransferase (NAT) activity, melatonin content and catecholamine levels were measured by means of radio-enzymatic, radioimmunoassay and high-performance liquid-chromatography methods, respectively. All three pineal parameters underwent significant declines following brief PVN stimulation during the night time. These observations lend credence to the view that the neural pathways transmitting light information to the sympathetic innervation controlling pineal melatonin synthesis. 22 references, 1more » figure.« less

Effect of pineal tetrapeptide on antioxidant defense in Drosophila melanogaster.

PubMed

Khavinson, V K; Myl'nikov, S V

2000-04-01

Effects of synthetic pineal tetrapeptide L-Ala-L-Glu-L-Asp-L-Glu (Epithalon) on specific catalase activity and the content of conjugated hydroperoxides in highly inbred Drosophila melanogaster lines differing in reproductive functions were studied. It was shown that Epithalon is a potent modulator of the antioxidant defense, whose biological activity 1000-fold surpasses that of the complex pineal peptide preparation Epithalamin.

Possible role of pineal allopregnanolone in Purkinje cell survival

PubMed Central

Haraguchi, Shogo; Hara, Sakurako; Ubuka, Takayoshi; Mita, Masatoshi; Tsutsui, Kazuyoshi

2012-01-01

It is believed that neurosteroids are produced in the brain and other nervous systems. Here, we show that allopregnanolone (ALLO), a neurosteroid, is exceedingly produced in the pineal gland compared with the brain and that pineal ALLO acts on the Purkinje cell, a principal cerebellar neuron, to prevent apoptosis in the juvenile quail. We first demonstrated that the pineal gland is a major organ of neurosteroidogenesis. A series of experiments using molecular and biochemical techniques has further demonstrated that the pineal gland produces a variety of neurosteroids de novo from cholesterol in the juvenile quail. Importantly, ALLO was far more actively produced in the pineal gland than in the brain. Pinealectomy (Px) decreased ALLO concentration in the cerebellum and induced apoptosis of Purkinje cells, whereas administration of ALLO to Px quail chicks prevented apoptosis of Purkinje cells. We further found that Px significantly increased the number of Purkinje cells that expressed active caspase-3, a key protease in apoptotic pathway, and daily injection of ALLO to Px quail chicks decreased the number of Purkinje cells expressing active caspase-3. These results indicate that the neuroprotective effect of pineal ALLO is associated with the decrease in caspase-3 activity during the early stage of neuronal development. We thus provide evidence that the pineal gland is an important neurosteroidogenic organ and that pineal ALLO may be involved in Purkinje cell survival during development. This is an important function of the pineal gland in the formation of neuronal circuits in the developing cerebellum. PMID:23213208

The photoreceptive cells of the pineal gland in adult zebrafish (Danio rerio).

PubMed

Laurà, Rosaria; Magnoli, Domenico; Zichichi, Rosalia; Guerrera, Maria Cristina; De Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

2012-03-01

The zebrafish pineal gland plays a fundamental role in the regulation of the circadian rhythm through the melatonin secretion. The pinealocytes, also called photoreceptive cells, are considered the morphofunctional unit of pineal gland. In literature, the anatomical features, the cellular characteristics, and the pinealocytes morphology of zebrafish pineal gland have not been previously described in detail. Therefore, this study was undertaken to analyze the structure and ultrastructure, as well as the immunohistochemical profile of the zebrafish pineal gland with particular reference to the pinealocytes. Here, we demonstrated, using RT-PCR, immunohistochemistry and transmission electron microscopy, the expression of the mRNA for rhodopsin in the pineal gland of zebrafish, as well as its cellular localization exclusively in the pinealocytes of adult zebrafish. Moreover, the ultrastructural observations demonstrated that the pinealocytes were constituted by an outer segment with numerous lamellar membranes, an inner segment with many mitochondria, and a basal pole with the synapses. Our results taken together demonstrated a central role of zebrafish pinealocytes in the control of pineal gland functions. Copyright © 2011 Wiley Periodicals, Inc.

Rax : developmental and daily expression patterns in the rat pineal gland and retina.

PubMed

Rohde, Kristian; Klein, David C; Møller, Morten; Rath, Martin F

2011-09-01

Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day 18, whereas Rax expression in the pineal is relatively delayed and not detectable until embryonic day 20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes to phenotype maintenance in the mature retina and pineal gland and may facilitate 24-h changes in the pineal transcriptome. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Rhodopsin Kinase Activity in the Mammalian Pineal Gland and Other Tissues

NASA Astrophysics Data System (ADS)

Somers, Robert L.; Klein, David C.

1984-10-01

Rhodopsin kinase, an enzyme involved in photochemical transduction in the retina, has been found in the mammalian pineal gland in amounts equal to those in the retina; other tissues had 7 percent of this amount, or less. This finding suggests that, in mammals, rhodopsin kinase functions in the pineal gland and other tissues to phosphorylate rhodopsin-like integral membrane receptors and is thereby involved in signal transduction.

Role of the Pineal Body Hormone in Thyroid Function; L'HORMONE EPIPHSAIRE INTERVIENT DANS LA DYNAMIQUE DU METABOLISME DE L'IODE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milcou, S.M.; Costiner, E. et al.

To evaluate the action of the pineal body hormone on thyroid function, hyperactivity of the epiphysis was experimentally induced by administering pineal body hormone four hours before the experiment and then every four hours during the experiment. Iodine tagging was achieved by the intraperltoneal injection of carrierless'' I/sup 131/. The animals, which had been divided into batches of 10, were sacrificed every 2 hours until 48 hours had elapsed following the radioactive tagging. Measurements on the radioactivity of the thyroid and of the blood were carried out in vitro. The values obtained were used in order to draw up simultaneousmore » radioactivity curves applicable to the total radioactivity and to that attributable to inorganic and organic iodine, respectively. The curves showing the variation in the radioactivity reveal a delayed action of the pineal gland hormone which is different according to whether the functional thyroid units have a large or small time constant. (auth)« less

Pineal Photoreceptor Cells Are Required for Maintaining the Circadian Rhythms of Behavioral Visual Sensitivity in Zebrafish

PubMed Central

Li, Xinle; Montgomery, Jake; Cheng, Wesley; Noh, Jung Hyun; Hyde, David R.; Li, Lei

2012-01-01

In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry)] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity. PMID:22815753

Diagnosis and treatment of pineal region tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuwelt, E.A.

The aim of this volume is to review the pertinent literature dealing with pineal tumors and thus aid in the handling of these rather uncommon lesions. After the first, introductory, chapter, three chapters treat the pathology and diagnosis of pineal tumors. There is also one chapter on intracranial germ cell tumors (natural history and pathogenesis) and one on the normal function of the pineal gland. With the exception of the chapter on diagnostic radiology of pineal tumors, which seems somewhat superficial, these five chapters summarize current knowledge about the nature of these complex lesions and their symptomatology very well. Themore » next nine chapters deal with biopsy and surgery of these tumors and how to manage the patient. The first of these gives a historical review of the development of surgical techniques - from the first attempt by Horsley in 1905 to the microsurgical techniques of today. It is followed by a very important and detailed description of the microsurgical anatomy of the pineal region.« less

Axelrod, the pineal and the melatonin hypothesis: lessons of 50 years to shape chronodisruption research.

PubMed

Erren, Thomas C; Reiter, Russel J

2010-01-01

With key work in the 1950s and 1960s, the 1970 Nobel laureate Julius Axelrod made major contributions to the development of pineal science. Looking back at some of his accomplishments in and for the field, we feel that lessons can be derived for future work regarding impairments of the pineal gland's and melatonin's many functions for promoting health and preventing disease in man.

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

PubMed

Bumb, Jan M; Schilling, Claudia; Enning, Frank; Haddad, Leila; Paul, Franc; Lederbogen, Florian; Deuschle, Michael; Schredl, Michael; Nolte, Ingo

2014-06-01

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. © 2014 European Sleep Research Society.

Melatonin, The Pineal Gland and Circadian Rhythms

DTIC Science & Technology

1992-04-30

physiological rhythms including locomotion, sleep/wake, thermoregulation , car- diovascular function and many endocrine processes. Among the rhythms under SCN...control of a wide array of behavioral and physiological rhythms including locomotion, sleep/wake, thermoregulation , cardiovascular function and many... reptiles and birds, overt rhythmicity results from the integration of multiple circadian oscillators within the pineal gland, eyes and the presumed

Historical and cultural aspects of the pineal gland: comparison between the theories provided by Spiritism in the 1940s and the current scientific evidence.

PubMed

Lucchetti, Giancarlo; Daher, Jorge C; Iandoli, Decio; Gonçalves, Juliane P B; Lucchetti, Alessandra L G

2013-01-01

Significance has been attached to the pineal gland in numerous different cultures and beliefs. One religion that has advanced the role of the pineal gland is Spiritism. The objective of the present study was to compile information on the pineal gland drawing on the books of Francisco Cândido Xavier written through psychography and to carry out a critical analysis of their scientific bases by comparing against evidence in the current scientific literature. A systematic search using the terms "pineal gland" and "epiphysis" was conducted of 12 works allegedly dictated by the spirit "André Luiz". All information on the pineal having potential correlation with the field of medicine and current studies was included. Specialists in the area were recruited to compile the information and draw parallels with the scientific literature. The themes related to the pineal gland were: mental health, reproductive function, endocrinology, relationship with physical activity, spiritual connection, criticism of the theory that the organ exerts no function, and description of a hormone secreted by the gland (reference alluding to melatonin, isolated 13 years later). The historical background for each theme was outlined, together with the theories present in the Spiritist books and in the relevant scientific literature. The present article provides an analysis of the knowledge the scientific community can acquire from the history of humanity and from science itself. The process of formulating hypotheses and scientific theories can benefit by drawing on the cultural aspects of civilization, taking into account so-called non-traditional reports and theories.

The Bioelectromagnetics Society Annual Meeting (11th) Held at Tucson, Arizona on June 18-22, 1989: Abstracts

DTIC Science & Technology

1989-06-01

SESSION A-i: SYMPOSIUM ON ELF FIELDS AND NEURO- ENDOCRINE FUNCTION Moderator: B. W. Wilson A-i-I NEUROENDOCRINE CONSEQUENCES OF PINEAL GLAND ...Antonio, TX 78284-7762. The pineal gland of animals and humans produces its chief hormonal product, melatonin, in a circadian manner with maximal...photoperiodic environment with the eyes perceiving the light which regulates the rhythm. The neural connections between the eyes and the pineal gland which

Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture.

PubMed

Khavinson, V Kh; Linkova, N S; Chalisova, N I; Dudkov, A V; Koncevaya, E A

2011-11-01

We demonstrated the influence of short peptides on the expression of signaling molecules in organotypic culture of the pineal gland from 3-month-old rats. Peptides Ala-Glu-Asp-Gly and Lys-Glu-Asp stimulate the expression of proliferative protein Ki-67 in pineal gland culture. These peptides as well as Glu-Asp-Arg and Lys-Glu do not affect the expression of apoptosis marker AIF. The synthesis of transcription factor CGRP by pinealocytes was stimulated only by Ala-Glu-Asp-Gly. Thus, peptide Ala-Glu-Asp-Gly tissue-specifically stimulates proliferative and secretory activities of pinealocytes, which can be used for recovery of pineal gland functions at the molecular level.

[The historical background of the pineal gland: I. From a spiritual valve to the seat of the soul].

PubMed

López-Muñoz, Francisco; Marín, Fernando; Alamo, Cecilio

Throughout history, the special anatomical location of the pineal gland in the central nervous system has given rise to a number of physiological hypotheses regarding the functional role of this organ. In classical ancient times, the pineal body (conarium) was considered to be a sort of valve-like sphincter that regulated the flow of the spiritus animalis at the ventricular level. But it was not until the 17th century that the pineal gland finally reached its highest levels of physiological significance, when Rene Descartes considered it to be the anatomical structure that housed the seat of the soul. The Cartesian hypotheses regarding the pineal gland did not arouse much interest in the scientific community of the time, and attention to this organ dwindled from then until the 20th century, when its neuroendocrinological nature was finally confirmed.

Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

PubMed Central

Ben-Moshe, Zohar; Foulkes, Nicholas S.

2014-01-01

The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. PMID:24839600

LIMITED RECOVERY OF PINEAL FUNCTION AFTER REGENERATION OF PREGANGLIONIC SYMPATHETIC AXONS: EVIDENCE FOR LOSS OF GANGLIONIC SYNAPTIC SPECIFICITY

PubMed Central

Lingappa, Jaisri R.; Zigmond, Richard E.

2013-01-01

The cervical sympathetic trunks (CST) contain axons of preganglionic neurons that innervate the superior cervical ganglia (SCG). Since, regeneration of CST fibers can be extensive and can reestablish certain specific patterns of SCG connections, restoration of end organ function would be expected. This expectation was examined with respect to the pineal gland, an organ innervated by the two SCG. The activity of pineal serotonin N-acetyltransferase (NAT) exhibits a large circadian rhythm, with activity high at night, which is dependent on the gland’s sympathetic input. Thirty six hours after the CST were crushed bilaterally, nocturnal NAT was decreased by 99%. Three months later, enzyme activity had recovered only to 15% of control values, a recovery dependent on regeneration of CST fibers. Nevertheless, a small day-night rhythm was present in lesioned animals. Neither the density of the gland’s adrenergic innervation nor the ability of an adrenergic agonist to stimulate NAT activity was reduced in rats with regenerated CST. In addition, stimulation of the regenerated CST at a variety of frequencies was at least as effective in increasing NAT activity as seen with control nerves. These data suggest that the failure of pineal function to recover is not due to a quantitative deficit in the extent of reinnervation or in synaptic efficacy. Rather, we suggest that there is some loss of specificity in the synaptic connections made in the SCG during reinnervation, resulting in a loss of the central neuronal information necessary for directing a normal NAT rhythm and thus normal pineal function. PMID:23486957

The Highly conserved gonadotropin-releasing hormone-2 form acts as a melatonin-releasing factor in the pineal of a teleost fish, the european sea bass Dicentrarchus labrax.

PubMed

Servili, Arianna; Lethimonier, Christèle; Lareyre, Jean-Jacques; López-Olmeda, José Fernando; Sánchez-Vázquez, Francisco Javier; Kah, Olivier; Muñoz-Cueto, José Antonio

2010-05-01

With the exception of modern mammals, most vertebrate species possess two GnRH genes, GnRH-1 and GnRH-2. In addition, in many teleost fish, there is a third gene called GnRH-3. If the main function of GnRH-1 is unambiguously to stimulate gonadotropin release, the other two GnRH forms still lack clear functions. This is particularly true for the highly conserved GnRH-2 that encodes chicken GnRH-II. This GnRH variant is consistently expressed in neurons of the dorsal synencephalon in most vertebrate groups but still has no clear functions supported by anatomical, pharmacological, and physiological data. In this study performed on a perciform fish, the European sea bass, we show for the first time that the pineal organ receives GnRH-2-immunoreactive fibers originating from the synencephalic GnRH-2 neurons. This was shown through a combination of retrograde tracing and immunohistochemistry, using highly specific antibodies. Supporting the presence of GnRH-2 functional targets, RT-PCR data together with the in situ hybridization studies showed that the sea bass pineal gland strongly expressed a GnRH receptor (dlGnRHR-II-2b) with clear selectivity for GnRH-2 and, to a lesser extent, the dlGnRHR-II-1a subtype. Finally, in vitro and in vivo experiments demonstrate stimulatory effects of GnRH-2 on nocturnal melatonin secretion by the sea bass pineal organ. Altogether, these data provide, for the first time in a vertebrate species, converging evidence supporting a role of GnRH-2 in the modulation of fish pineal functions.

Involvement of Lypge in the formation of eye and pineal gland in zebrafish.

PubMed

Ji, Dongrui; Wang, Su; Li, Mingyue; Zhang, Shicui; Li, Hongyan

2018-02-05

The proteins of Ly-6 (lymphocyte antigen-6) family are involved in the regulation of immunoreaction, cell migration and adhesion, and neuronal excitability. However, little is known about the function of Ly-6 proteins in embryogenesis. Herein, we identified a GPI anchored Ly-6 member named ly6 expressed in pineal gland and eye (lypge). Dynamic expression pattern of lypge was revealed by whole mount in situ hybridization. It was strikingly expressed in the pineal gland and cone photoreceptor, and its expression was regulated by orthodenticle homolog 5 (otx5) which has been shown to control the expression of many pineal genes. In addition, we demonstrated that lypge was rhythmically expressed in larvae from 4dpf on. Moreover, knockdown of lypge resulted in small head and small eye formed in zebrafish embryos. These suggest that Lypge is involved in the formation of the eye and pineal gland in early development of zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

Uptake and metabolism of indole compounds by the goldfish pineal organ

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNulty, J.A.

Indole metabolism was studied in the pineal organ of the goldfish by radioautography and high-performance liquid chromatography. The rate of uptake of tritiated serotonin was rapid in vitro with dense labeling over the photoreceptor cells. Tritiated tryptophan was taken up at a slower rate and the label was distributed evenly over the epithelium. Continual light caused a reduction in the concentration of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) compared to groups exposed to constant darkness both in vivo and in explants, suggesting that these effects are not derived from photoreceptors outside the pineal organ. These data are consistent with themore » hypothesis that indole metabolism is functionally linked to phototransduction events in the pineal organ of lower vertebrates.« less

Transducin Duplicates in the Zebrafish Retina and Pineal Complex: Differential Specialisation after the Teleost Tetraploidisation

PubMed Central

Lagman, David; Callado-Pérez, Amalia; Franzén, Ilkin E.

2015-01-01

Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation. PMID:25806532

Sleep–wake regulation and hypocretin–melatonin interaction in zebrafish

PubMed Central

Appelbaum, Lior; Wang, Gordon X.; Maro, Geraldine S.; Mori, Rotem; Tovin, Adi; Marin, Wilfredo; Yokogawa, Tohei; Kawakami, Koichi; Smith, Stephen J.; Gothilf, Yoav; Mignot, Emmanuel; Mourrain, Philippe

2009-01-01

In mammals, hypocretin/orexin (HCRT) neuropeptides are important sleep–wake regulators and HCRT deficiency causes narcolepsy. In addition to fragmented wakefulness, narcoleptic mammals also display sleep fragmentation, a less understood phenotype recapitulated in the zebrafish HCRT receptor mutant (hcrtr−/−). We therefore used zebrafish to study the potential mediators of HCRT-mediated sleep consolidation. Similar to mammals, zebrafish HCRT neurons express vesicular glutamate transporters indicating conservation of the excitatory phenotype. Visualization of the entire HCRT circuit in zebrafish stably expressing hcrt:EGFP revealed parallels with established mammalian HCRT neuroanatomy, including projections to the pineal gland, where hcrtr mRNA is expressed. As pineal-produced melatonin is a major sleep-inducing hormone in zebrafish, we further studied how the HCRT and melatonin systems interact functionally. mRNA level of arylalkylamine-N-acetyltransferase (AANAT2), a key enzyme of melatonin synthesis, is reduced in hcrtr−/− pineal gland during the night. Moreover, HCRT perfusion of cultured zebrafish pineal glands induces melatonin release. Together these data indicate that HCRT can modulate melatonin production at night. Furthermore, hcrtr−/− fish are hypersensitive to melatonin, but not other hypnotic compounds. Subthreshold doses of melatonin increased the amount of sleep and consolidated sleep in hcrtr−/− fish, but not in the wild-type siblings. These results demonstrate the existence of a functional HCRT neurons-pineal gland circuit able to modulate melatonin production and sleep consolidation. PMID:19966231

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

PubMed

Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

2011-08-01

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. © 2011 John Wiley & Sons A/S.

Morphologic variations in the pineal gland of the albino rat after a chronic alcoholisation process.

PubMed

Martínez-Salvador, J; Ruiz-Torner, A; Blasco-Serra, A; Martínez-Soriano, F; Valverde-Navarro, A A

2018-04-01

We studied the effect of alcohol on the pineal gland of 48 male Wistar rats. Animals were divided into control and experimental groups. The experimental group underwent a previous progressive alcoholisation period with ethanol diluted in water at a concentration of 40%. Animals were sacrificed at 3, 6, 9 and 12 months, and the ultrastructure, karyometric indices, and number of synaptic bodies in the pineal gland were analysed. The results showed progressive morphologic alterations in the ethanol-treated animals, which culminated in fatty degeneration of the pineal parenchyma after 6 months. The karyometric indices decreased in both the central and peripheral areas compared with the control group. Moreover, the seasonal rhythmicity observed in the controls disappeared in the experimental groups, whose number of different populations of synaptic bodies (synaptic ribbons and synaptic spherules) considerably lowered with inversion of their normal seasonal rhythm. These results support that chronic alcoholisation leads to fatty degeneration of the pineal parenchyma, and a considerable alteration in nuclear functional rhythms and synaptic bodies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gut Melatonin in Vertebrates: Chronobiology and Physiology.

PubMed

Mukherjee, Sourav; Maitra, Saumen Kumar

2015-01-01

Melatonin, following discovery in the bovine pineal gland, has been detected in several extra-pineal sources including gastrointestinal tract or gut. Arylalkylamine N-acetyltransferase (AANAT) is the key regulator of its biosynthesis. Melatonin in pineal is rhythmically produced with a nocturnal peak in synchronization with environmental light-dark cycle. A recent study on carp reported first that melatonin levels and intensity of a ~23 kDa AANAT protein in each gut segment also exhibit significant daily variations but, unlike pineal, show a peak at midday in all seasons. Extensive experimental studies ruled out direct role of light-dark conditions in determining temporal pattern of gut melatoninergic system in carp, and opened up possible role of environmental non-photic cue(s) as its synchronizer. Based on mammalian findings, physiological significance of gut-derived melatonin also appears unique because its actions at local levels sharing paracrine and/or autocrine functions have been emphasized. The purpose of this mini review is to summarize the existing data on the chronobiology and physiology of gut melatonin and to emphasize their relation with the same hormone derived in the pineal in vertebrates including fish.

The role of the pineal gland in the photoperiodic control of bird song frequency and repertoire in the house sparrow, Passer domesticus.

PubMed

Wang, Gang; Harpole, Clifford E; Paulose, Jiffin; Cassone, Vincent M

2014-04-01

Temperate zone birds are highly seasonal in many aspects of their physiology. In mammals, but not in birds, the pineal gland is an important component regulating seasonal patterns of primary gonadal functions. Pineal melatonin in birds instead affects seasonal changes in brain song control structures, suggesting the pineal gland regulates seasonal song behavior. The present study tests the hypothesis that the pineal gland transduces photoperiodic information to the control of seasonal song behavior to synchronize this important behavior to the appropriate phenology. House sparrows, Passer domesticus, expressed a rich array of vocalizations ranging from calls to multisyllabic songs and motifs of songs that varied under a regimen of different photoperiodic conditions that were simulated at different times of year. Control (SHAM) birds exhibited increases in song behavior when they were experimentally transferred from short days, simulating winter, to equinoctial and long days, simulating summer, and decreased vocalization when they were transferred back to short days. When maintained in long days for longer periods, the birds became reproductively photorefractory as measured by the yellowing of the birds' bills; however, song behavior persisted in the SHAM birds, suggesting a dissociation of reproduction from the song functions. Pinealectomized (PINX) birds expressed larger, more rapid increases in daily vocal rate and song repertoire size than did the SHAM birds during the long summer days. These increases gradually declined upon the extension of the long days and did not respond to the transfer to short days as was observed in the SHAM birds, suggesting that the pineal gland conveys photoperiodic information to the vocal control system, which in turn regulates song behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.

PubMed

Sharan, Kunal; Lewis, Kirsty; Furukawa, Takahisa; Yadav, Vijay K

2017-09-01

Tryptophan, an essential amino acid through a series of enzymatic reactions gives rise to various metabolites, viz. serotonin and melatonin, that regulate distinct biological functions. We show here that tryptophan metabolism in the pineal gland favors bone mass accrual through production of melatonin, a pineal-derived neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes the first step in the melatonin biosynthesis lead to a decrease in melatonin levels and a low bone mass due to an isolated decrease in bone formation while bone resorption parameters remained unaffected. Skeletal analysis of the mice deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/- and MT2-/- mice showed a cell intrinsic defect in the proliferation, differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT counterparts, and the mutant cells did not respond to melatonin addition. Finally, we demonstrate that daily oral administration of melatonin can increase bone accrual during growth and can cure ovariectomy-induced structural and functional degeneration of bone by specifically increasing bone formation. By identifying pineal-derived melatonin as a regulator of bone mass through MT2 receptors, this study expands the role played by tryptophan derivatives in the regulation of bone mass and underscores its therapeutic relevance in postmenopausal osteoporosis. © 2017 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd.

Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions.

PubMed

Koyanagi, Mitsumasa; Wada, Seiji; Kawano-Yamashita, Emi; Hara, Yuichiro; Kuraku, Shigehiro; Kosaka, Shigeaki; Kawakami, Koichi; Tamotsu, Satoshi; Tsukamoto, Hisao; Shichida, Yoshinori; Terakita, Akihisa

2015-09-15

Recent genome projects of various animals have uncovered an unexpectedly large number of opsin genes, which encode protein moieties of photoreceptor molecules, in most animals. In visual systems, the biological meanings of this diversification are clear; multiple types of visual opsins with different spectral sensitivities are responsible for color vision. However, the significance of the diversification of non-visual opsins remains uncertain, in spite of the importance of understanding the molecular mechanism and evolution of varied non-visual photoreceptions. Here, we investigated the diversification of the pineal photopigment parapinopsin, which serves as the UV-sensitive photopigment for the pineal wavelength discrimination in the lamprey, linking it with other pineal photoreception. Spectroscopic analyses of the recombinant pigments of the two teleost parapinopsins PP1 and PP2 revealed that PP1 is a UV-sensitive pigment, similar to lamprey parapinopsin, but PP2 is a blue-sensitive pigment, with an absorption maximum at 460-480 nm, showing the diversification of non-visual pigment with respect to spectral sensitivity. We also found that PP1 and PP2 exhibit mutually exclusive expressions in the pineal organs of three teleost species. By using transgenic zebrafish in which these parapinopsin-expressing cells are labeled, we found that PP1-expressing cells basically possess neuronal processes, which is consistent with their involvement in wavelength discrimination. Interestingly, however, PP2-expressing cells rarely possess neuronal processes, raising the possibility that PP2 could be involved in non-neural responses rather than neural responses. Furthermore, we found that PP2-expressing cells contain serotonin and aanat2, the key enzyme involved in melatonin synthesis from serotonin, whereas PP1-expressing cells do not contain either, suggesting that blue-sensitive PP2 is instead involved in light-regulation of melatonin secretion. In this paper, we have clearly shown the different molecular properties of duplicated non-visual opsins by demonstrating the diversification of parapinopsin with respect to spectral sensitivity. Moreover, we have shown a plausible link between the diversification and its physiological impact by discovering a strong candidate for the underlying pigment in light-regulated melatonin secretion in zebrafish; the diversification could generate a new contribution of parapinopsin to pineal photoreception. Current findings could also provide an opportunity to understand the "color" preference of non-visual photoreception.

RGS2 is a feedback inhibitor of melatonin production in the pineal gland

PubMed Central

Matsuo, Masahiro; Coon, Steven L.; Klein, David C.

2014-01-01

The 24-h rhythmic production of melatonin by the pineal gland is essential for coordinating circadian physiology. Melatonin production increases at night in response to the release of norepinephrine from sympathetic nerve processes which innervate the pineal gland. This signal is transduced through G-protein-coupled adrenergic receptors. Here, we found that the abundance of regulator of G-protein signaling 2 (RGS2) increases at night, that expression is increased by norepinephrine and that this protein has a negative feedback effect on melatonin production. These data are consistent with the conclusion that RGS2 functions on a daily basis to negatively modulate melatonin production. PMID:23523917

An historical view of the pineal gland and mental disorders.

PubMed

López-Muñoz, F; Molina, J D; Rubio, G; Alamo, C

2011-08-01

Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was "the three cells of the brain", in which the pineal gland was even called the "appendix of thought". The pineal gland could also be associated with the boom, during this period, of certain legends about the "stone of folly". But the most relevant psychopathological role of this organ arrived with Descartes, who proposed that it was the seat of the human soul and controlled communications between the physical body and its surroundings, including emotions. After a period of decline during which it was considered as a mere vestigial remnant of evolution, the link between the pineal gland and psychiatric disorders was definitively highlighted in the 20th century, first with the use of glandular extracts in patients with mental deficiency, and finally with the discovery of melatonin in 1958. The physiological properties of melatonin reawakened interest in the relationship between the pineal gland and mental disorders, fundamentally the affective and sleep disorders, which culminated in the development of new pharmacological agents acting through melatonergic receptors (ramelteon and agomelatine). Copyright © 2011 Elsevier Ltd. All rights reserved.

CSF generation by pineal gland results in a robust melatonin circadian rhythm in the third ventricle as an unique light/dark signal.

PubMed

Tan, Dun-Xian; Manchester, Lucien C; Reiter, Russel J

2016-01-01

Pineal gland is an important organ for the regulation of the bio-clock in all vertebrate species. Its major secretory product is melatonin which is considered as the chemical expression of darkness due to its circadian peak exclusively at night. Pineal melatonin can be either released into the blood stream or directly enter into the CSF of the third ventricle via the pineal recess. We have hypothesized that rather than the peripheral circulatory melatonin circadian rhythm serving as the light/dark signal, it is the melatonin rhythm in CSF of the third ventricle that serves this purpose. This is due to the fact that melatonin circadian rhythm in the CSF is more robust in terms of its extremely high concentration and its precise on/off peaks. Thus, extrapineal-generated melatonin or diet-derived melatonin which enters blood would not interfere with the bio-clock function of vertebrates. In addition, based on the relationship of the pineal gland to the CSF and the vascular structure of this gland, we also hypothesize that pineal gland is an essential player for CSF production. We feel it participates in both the formation and reabsorption of CSF. The mechanisms associated with these processes are reviewed and discussed in this brief review. Copyright © 2015 Elsevier Ltd. All rights reserved.

A novel function for the pineal organ in the control of swim depth in the Atlantic halibut larva

NASA Astrophysics Data System (ADS)

Novales Flamarique, Iñigo

2002-02-01

The pineal organ of vertebrates is a photo-sensitive structure that conveys photoperiod information to the brain. This information influences circadian rhythm and related metabolic processes such as thermoregulation, hatching time, body growth, and the timing of reproduction. This study demonstrates extra-ocular light responses that control swim depth in the larva of the Atlantic halibut, Hyppoglosus hyppoglosus. Young larvae without a functional eye (<29 days) swim upwards after an average delay of 5 s following the onset of a downwelling light stimulus, but sink downwards a few seconds later. Older larvae (>=29 days), which possess a functional eye, swim immediately downwards (microsecond delay) following the onset of the light stimulus, but proceed to swim upwards several seconds later. These two response patterns are thus opposite in polarity and have different time kinetics. Because the pineal organ of the Atlantic halibut develops during the embryonic stage, and because it is the only centre in the brain that expresses functional visual pigments (opsins) at early larval stages, it is the only photosensory organ capable of generating the extra-ocular responses observed.

Pregnancy outcome in heat-exposed hamsters; the involvement of the pineal.

PubMed

Kaplanski, J; Zohar, R; Sod-Moriah, U A; Magal, E; Hirschmann, N; Nir, I

1988-01-01

The effect of high ambient temperature (34 degrees C) on the function of the female reproductive system, on embryonic development and on outcome of pregnancy, was investigated in heat-exposed sham-operated (Sh) and pinealectomized (Px) golden hamsters maintained under short photoperiod. Plasma prolactin levels were reduced in both heat-exposed groups (ShH and PxH) but pituitary prolactin was increased in the pinealectomized groups irrespective of ambient temperature (21 or 34 degrees C). Pituitary weights and LH contents were not affected in any test group. Heat exposure brought about a reduction in the number of corpora lutea and of pups born, the latter being more drastically reduced in absence of the pineal; the depressant effect of heat on ovarian weight was evident only in the pinealectomized animals. Progesterone levels were not affected in any test group and pregnancy was not prolonged, thus, it would seem that pregnant hamsters adapt themselves well to heat. Moreover, high ambient temperature promoted a rise in pineal. HIOMT activity and boosted cortisol levels in presence of the pineal gland only, which, together with the above findings, shows that the pineal can provide protection for pregnant hamsters against adverse effects of high ambient temperature.

Cartesian theories on the passions, the pineal gland and the pathogenesis of affective disorders: an early forerunner.

PubMed

López-Muñoz, F; Alamo, C

2011-03-01

The relationship between physical and functional alterations in the pineal gland, the 'passions' (emotions or feelings) and psychopathology has been a constant throughout the history of medicine. One of the most influential authors on this subject was René Descartes, who discussed it in his work The Treatise on the Passions of the Soul (1649). Descartes believed that 'passions' were sensitive movements that the soul, located in the pineal gland, experienced due to its union with the body, by circulating animal spirits. Descartes described sadness as one of the six primitive passions of the soul, which leads to melancholy if not remedied. Cartesian theories had a great deal of influence on the way that mental pathologies were considered throughout the entire 17th century and during much of the 18th century, but the link between the pineal gland and psychiatric disorders it was definitively highlighted in the 20th century, with the discovery of melatonin in 1958. The recent development of a new pharmacological agent acting through melatonergic receptors (agomelatine) has confirmed the close link between the pineal gland and affective disorders.

State of some peripheral organs during laser puncture correction of ovarian functional deficiency

NASA Astrophysics Data System (ADS)

Vylegzhanina, T. A.; Kuznetsova, Tatiana I.; Maneeva, O.; Ryzhkovskaya, E. L.; Yemelianova, A.

2001-01-01

The findings from studies on structural and functional parameters of the adrenal, thyroid, and pineal glands in conditions of ovarian hypofunction and after its correction by laser puncture are presented. An experimentally induced hypofunction of the ovaries was shown to be accompanied by a decreased hormonal synthesis in the cortical fascicular zone. The epiphysis showed ultra structural signs of increased functional activity. Application of a helium-neon laser to biologically active points of the ovarian reflexogenic zone induced normalization of the ovarian cycle, potentiating of the adrenal functional state, and a decreased thyroid hormone production and abolished the activatory effect of the dark regime on the functional state of the pineal gland.

Immunopathology of pineal glands from horses with uveitis.

PubMed

Kalsow, C M; Dubielzig, R R; Dwyer, A E

1999-06-01

Pinealitis accompanying uveitis is well established in laboratory models of experimental autoimmune uveoretinitis. In naturally occurring uveitis, pinealitis has been demonstrated in the pineal gland from a mare with active uveitis and is suspected in some human uveitides. We have evaluated pineal glands from horses with various stages of uveitis for signs of immunopathology accompanying spontaneous uveitis. Pineal glands from 10 horses with uveitis and from 13 horses without uveitis were evaluated for histochemical (H&E, collagen) and immunohistochemical (MHC class II antigen expression, infiltration of T and B lymphocytes, and glial fibrillary acidic protein (GFAP) and vimentin upregulation) evidence of inflammation. Septal areas of pineal glands from horses with uveitis had clusters of MHC class II antigen-expressing cells, T lymphocytes, and enhanced collagen deposition. These changes were not as readily observed in pineal glands from horses without uveitis. B lymphocytes were detected only in the pineal gland from the one mare with active uveitis in which T and B lymphocytes were organized into follicles. No differences in GFAP or vimentin immunoreactivity were noted in pineal glands from horses with or without uveitis. These pineal gland changes suggest that the pinealitis associated with equine uveitis is transient just as the uveitis of these horses is recurrent. Study of pineal glands from horses with clinically documented uveitis allows demonstration of subtle pineal changes associated with natural uveitis. Similar changes would be difficult to document in human patient populations.

Fine structure of the free-living parakeet pineal in relation to the breeding cycle.

PubMed

Prasadan, T N; Kotak, V C

1993-10-01

Seasonal changes in the ultrastructure of the free-living Rose-Ringed Parakeet Psittacula krameri pineal were examined in relation to the sub-tropical environment and seasonal reproduction. Dark and light pinealocytes of the presumptive neuroendocrine cell line predominated, while supporting cells, ependymal cells, myelinated and non-myelinated nerve fibers with nerve endings, and regressed photoreceptor elements were also observed. Unlike in pineals of many animals, particularly mammals, the presence of dense-core vesicles (DCVs) with varying core density, and absence of clear vesicles and vacuoles with flocullent material, indicate the involvement of DCVs in the synthesis and secretion of pineals principle/s. In November (pre-breeding) when the day length registered a drop to LD 10:14, pinealocytes showed significantly decreased and smaller DCVs and mitochondria, nuclei with heterochromatin, and greater distribution of glycogen and lipid droplets, all indicating low pineal metabolic activity. During the shortest day regime from December to March, when the birds peaked breeding, the number and size of DCVs and mitochondria increased, and Golgi body-endoplasmic reticulum-lysosome complex (GERL) was very well defined. Images of DCVs suggested possible secretion of pineal principle/s by dissolution, and exocytosis. Coincidence of these features with peak gonadotrophic (circulating LH) and spermatogenic and testicular endocrine activity described previously suggested an active turnover of pineal products during this short day length regime when parakeets breed. In contrast, during the post-breeding season (April onwards), when the day-length increased to LD 13:11 and hypophyseal-gonadal function was down, nuclei and RER continued to show active profile, the Golgi body and associated complex were moderately seen, and the DCVs and mitochondria were significantly smaller and lesser. It is therefore probable that the pineal is an important relay to translate cues related to less drastic sub-tropical environmental change into DCV-linked neurohormones that in turn may be involved in modulating seasonal breeding in parakeets.

TransRapid TR-07 maglev-spectrum magnetic field effects on daily pineal indoleamine metabolic rhythms in rodents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groh, K.R.

This study examined the effects on pineal function of magnetic field (MF) exposures (ac and dc components) similar to those produced by the TransRapid TR-07 and other electromagnetic maglev systems (EMS). Rats were entrained to a light-dark cycle and then exposed to a continuous, or to an inverted, intermittent (on = 45 s, off = 15 s, induced current = 267 G/s) simulated multifrequency ac and dc magnetic field (MF) at 1 or 7 times the TR-07 maglev vehicle MF intensity for 2 hr. Other groups of rats were exposed to only the ac or the dc-component of the maglevmore » MF. For comparison, one group was exposed to an inverted, intermittent 60-Hz MF. Each group was compared to an unexposed group of rats for changes in pineal melatonin and serotonin-N-acetyltransferase (NAT). MF exposures at an intensity equivalent to that produced by the TR-07 vehicle had no effect on melatonin or NAT compared with sham-exposed animals under any of the conditions examined. However, 7X TR-07-level continuous 2-h MF exposures significantly depressed pineal NAT by 45%. Pineal melatonin was also depressed 33--43% by a continuous 7X TR-07 MF exposure and 28% by an intermittent 60-Hz 850-mG MF, but the results were not statically significant. This study demonstrates that intermittent, combined ac and dc MFs similar to those produced by the TR-07 EMS maglev vehicle alter the normal circadian rhythm of pineal indoleamine metabolism. The pineal regulatory enzyme NAT was more sensitive to MF exposure than melatonin and may be a more desirable measure of the biological effects of MF exposure.« less

MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase.

PubMed

Clokie, Samuel J H; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L; Klein, David C

2012-07-20

MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ~75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3"-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis.

Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness.

PubMed

Ikegami, Taro; Maruyama, Yusuke; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

2015-01-01

Melatonin receptor gene expression as well as melatonin synthesis and secretion activities were examined in the pineal gland of the grass puffer, which exhibits unique lunar/tidal cycle-synchronized mass spawing: spawning occurs before high tide on the day of spring tide during spawing season. Melatonin synthesizing activity was assessed by the abundance of arylalkylamine N-acetyltransferase 2 (AANAT2) mRNA. The amount of aanat2 mRNA was low during light phase and initiated to increase after the light was turned off. The secretion of melatonin from primary pineal organ culture was stimulated after the light was turned off and ceased immediately after the light was turned on. The expression levels of four melatonin receptor subtype genes (mel 1a 1.4, mel 1a 1.7, mel1b, and mel1c) showed synchronous variations, and the levels tended to be high during the dark phase under light/dark conditions. These results suggest that the action of melatonin on the pineal gland is highly dependent on light and photoperiod, possibly with stronger action during night time. Under constant darkness, the expression of four melatonin receptor subtype genes showed unique ultradian oscillations with the period of 14.0-15.4 h, suggesting the presence of a circatidal oscillator in the pineal gland. The present results indicate that melatonin may serve local chronobiological functions in the pineal gland. These cyclic expressions of melatonin receptor genes in the pineal gland may be important in the control of the lunar/tidal cycle-synchronized mass spawning in the grass puffer.

Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness

PubMed Central

Ikegami, Taro; Maruyama, Yusuke; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

2015-01-01

Melatonin receptor gene expression as well as melatonin synthesis and secretion activities were examined in the pineal gland of the grass puffer, which exhibits unique lunar/tidal cycle-synchronized mass spawing: spawning occurs before high tide on the day of spring tide during spawing season. Melatonin synthesizing activity was assessed by the abundance of arylalkylamine N-acetyltransferase 2 (AANAT2) mRNA. The amount of aanat2 mRNA was low during light phase and initiated to increase after the light was turned off. The secretion of melatonin from primary pineal organ culture was stimulated after the light was turned off and ceased immediately after the light was turned on. The expression levels of four melatonin receptor subtype genes (mel1a1.4, mel1a1.7, mel1b, and mel1c) showed synchronous variations, and the levels tended to be high during the dark phase under light/dark conditions. These results suggest that the action of melatonin on the pineal gland is highly dependent on light and photoperiod, possibly with stronger action during night time. Under constant darkness, the expression of four melatonin receptor subtype genes showed unique ultradian oscillations with the period of 14.0–15.4 h, suggesting the presence of a circatidal oscillator in the pineal gland. The present results indicate that melatonin may serve local chronobiological functions in the pineal gland. These cyclic expressions of melatonin receptor genes in the pineal gland may be important in the control of the lunar/tidal cycle-synchronized mass spawning in the grass puffer. PMID:25688184

MicroRNAs in the Pineal Gland

PubMed Central

Clokie, Samuel J. H.; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L.; Klein, David C.

2012-01-01

MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ∼75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3′-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis. PMID:22908386

Lymphopoiesis in the chicken pineal gland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cogburn, L.A.; Glick, B.

Pineal lymphoid development was studied in two breeds of chickens from hatching until sexual maturity. No lymphocytes were found in the pineal prior to 9 days of age (da). Lymphocytes migrate through the endothelium of venules into the pineal stroma. Lymphoid tissue reached its maximal accumulation in 32-da pineal glands of both breeds. At this age, the New Hampshire (NH) breed had a larger proportion of lymphoid volume to total pineal volume (32%) than did pineal glands from White Leghorn (WL) chickens (18%).

[Characteristics of the pineal gland and thymus relationship in aging].

PubMed

Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M; Trofimov, A V; Sevost'ianova, N N

2011-01-01

The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

N,N-dimethyltryptamine and the pineal gland: Separating fact from myth.

PubMed

Nichols, David E

2018-01-01

The pineal gland has a romantic history, from pharaonic Egypt, where it was equated with the eye of Horus, through various religious traditions, where it was considered the seat of the soul, the third eye, etc. Recent incarnations of these notions have suggested that N,N-dimethyltryptamine is secreted by the pineal gland at birth, during dreaming, and at near death to produce out of body experiences. Scientific evidence, however, is not consistent with these ideas. The adult pineal gland weighs less than 0.2 g, and its principal function is to produce about 30 µg per day of melatonin, a hormone that regulates circadian rhythm through very high affinity interactions with melatonin receptors. It is clear that very minute concentrations of N,N-dimethyltryptamine have been detected in the brain, but they are not sufficient to produce psychoactive effects. Alternative explanations are presented to explain how stress and near death can produce altered states of consciousness without invoking the intermediacy of N,N-dimethyltryptamine.

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

PubMed

Han, Qing; Li, Youqiong; Wang, Jincheng; Zhao, Xue

2018-03-30

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. 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. In 198 subjects, the mean length, width, and height of pineal gland were 7.58 ± 0.45 mm, 4.92 ± 0.40 mm, and 2.90 ± 0.20 mm. The distances between pineal gland and superior colliculus as well as splenium of corpus callosum were 3.96 ± 0.92 mm and 4.3 ± 1.89 mm, respectively. The PGV was 54.1 ± 7.02 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. 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.

Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.

PubMed

Magnoli, Domenico; Zichichi, Rosalia; Laurà, Rosaria; Guerrera, Maria Cristina; Campo, Salvatore; de Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

2012-03-09

The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan. Copyright © 2012 Elsevier B.V. All rights reserved.

Pinealitis accompanying equine recurrent uveitis.

PubMed Central

Kalsow, C M; Dwyer, A E; Smith, A W; Nifong, T P

1993-01-01

There is no direct verification of pineal gland involvement in human uveitis. Specimens of pineal tissue are not available during active uveitis in human patients. Naturally occurring uveitis in horses gives us an opportunity to examine tissues during active ocular inflammation. We examined the pineal gland of a horse that was killed because it had become blind during an episode of uveitis. The clinical history and histopathology of the eyes were consistent with post-leptospiral equine recurrent uveitis. The pineal gland of this horse had significant inflammatory infiltration consisting mainly of lymphocytes with some eosinophils. This observation of pinealitis accompanying equine uveitis supports the animal models of experimental autoimmune uveoretinitis with associated pinealitis and suggests that the pineal gland may be involved in some human uveitides. Images PMID:8435400

Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma.

PubMed

Li, Jun; Wang, Ping; Wang, Bin

2016-05-01

Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma.The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement.The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma.This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement.

Endocrine rhythms in the brown bear (Ursus arctos): Evidence supporting selection for decreased pineal gland size

PubMed Central

Ware, Jasmine V; Nelson, O Lynne; Robbins, Charles T; Carter, Patrick A; Sarver, Brice A J; Jansen, Heiko T

2013-01-01

Many temperate zone animals adapt to seasonal changes by altering their physiology. This is mediated in large part by endocrine signals that encode day length and regulate energy balance and metabolism. The objectives of this study were to determine if the daily patterns of two important hormones, melatonin and cortisol, varied with day length in captive brown bears (Ursus arctos) under anesthetized and nonanesthetized conditions during the active (March–October) and hibernation periods. Melatonin concentrations varied with time of day and season in nonanesthetized female bears despite exceedingly low nocturnal concentrations (1–4 pg/mL) in the active season. In contrast, melatonin concentrations during hibernation were 7.5-fold greater than those during the summer in anesthetized male bears. Functional assessment of the pineal gland revealed a slight but significant reduction in melatonin following nocturnal light application during hibernation, but no response to beta-adrenergic stimulation was detected in either season. Examination of pineal size in two bear species bears combined with a phylogenetically corrected analysis of pineal glands in 47 other species revealed a strong relationship to brain size. However, pineal gland size of both bear species deviated significantly from the expected pattern. Robust daily plasma cortisol rhythms were observed during the active season but not during hibernation. Cortisol was potently suppressed following injection with a synthetic glucocorticoid. The results suggest that melatonin and cortisol both retain their ability to reflect seasonal changes in day length in brown bears. The exceptionally small pineal gland in bears may be the result of direct or indirect selection. PMID:24303132

LIM homeobox transcription factor Isl1 is required for melatonin synthesis in the pig pineal gland.

PubMed

Zhang, Jinglin; Qiu, Jingtao; Zhou, Yewen; Wang, Yue; Li, Hongjiao; Zhang, Taojie; Jiang, Ying; Gou, Kemian; Cui, Sheng

2018-02-26

Melatonin is a key hormone that regulates circadian rhythms, metabolism, and reproduction. However, the mechanisms of melatonin synthesis and secretion have not been fully defined. The purpose of this study was to investigate the functions of the LIM homeobox transcription factor Isl1 in regulating melatonin synthesis and secretion in porcine pineal gland. We found that Isl1 is highly expressed in the melatonin-producing cells in the porcine pineal gland. Further functional studies demonstrate that Isl1 knockdown in cultured primary porcine pinealocytes results in the decline of melatonin and arylalkylamine N-acetyltransferase (AANAT) mRNA levels by 29.2% and 72.2%, respectively, whereas Isl1 overexpression raised by 1.3-fold and 2.7-fold. In addition, the enhancing effect of norepinephrine (NE) on melatonin synthesis was abolished by Isl1 knockdown. The in vivo intracerebroventricular NE injections upregulate Isl1 mRNA and protein levels by about threefold and 4.5-fold in the porcine pineal gland. We then examined the changes in Isl1 expression in the pineal gland and global melatonin levels throughout the day. The results show that Isl1 protein level at 24:00 is 2.5-fold higher than that at 12:00, which is parallel to melatonin levels. We further found that Isl1 increases the activity of AANAT promoter, and the effect of NE on Isl1 expression was blocked by an ERK inhibitor. Collectively, the results presented here demonstrate that Isl1 positively modulates melatonin synthesis by targeting AANAT, via the ERK signaling pathway of NE. These suggest that Isl1 plays important roles in maintaining the daily circadian rhythm. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Daytime Unresponsiveness of the Human and Syrian Hamster Pineal to Adrenergic Stimulation

DTIC Science & Technology

1989-01-01

exposure) raises pineal melatonin content; injection outside this sensitive period does not. (CajP-" This dramatic change in response of the pineal gland ...1988, 264 (abstract976). Binkley, S. (1976): Comprative biochemistry of the pineal glands of birds and mammals. Am. Zool. 16, 57-65. Bowers, C.V., an...R.J. (1982): In vivo responses of the pineal gland of the Syrian hamster to isoproterenol or -or-epinephrine. In The Pineal and Its Hormones, pp 107

Pineal gland volume in schizophrenia and mood disorders.

PubMed

Fındıklı, Ebru; Inci, Mehmet Fatih; Gökçe, Mustafa; Fındıklı, Hüseyin Avni; Altun, Hatice; Karaaslan, Mehmet Fatih

2015-06-01

The majority of patients with schizophrenia and mood disorders have disruptions in sleep and circadian rhythm. Melatonin, which is secreted by the human pineal gland, plays an important role in sleep and circadian rhythm. The aim of the present study was to evaluate and compare pineal gland volumes in patients with schizophrenia and mood disorders. We retrospectively evaluated the pineal gland volumes of 80 cases, including 16 cases of unipolar depression, 17 cases of bipolar disorder, 17 cases of schizophrenia, and 30 controls. The total pineal gland volume of all cases was measured via magnetic resonance images, and the total mean pineal volume of each group was compared. The mean pineal volumes of patients with schizophrenia, bipolar disorder, unipolar depression, and the controls were 83.55±10.11 mm(3), 93.62±11.00 mm(3), 95.19±11.61 mm(3) and 99.73±12.03 mm(3), respectively. The mean pineal gland volume of the patients with schizophrenia was significantly smaller than those of the other groups. Our data show that patients with schizophrenia have smaller pineal gland volumes, and this deviation in pineal gland morphology is not seen in those with mood disorders. We hypothesize that volumetric changes in the pineal gland of patients with schizophrenia may be involved in the pathophysiology of this illness.

Cellular lining of the sheep pineal recess studied by light-, transmission-, and scanning electron microscopy: morphologic indications for a direct secretion of melatonin from the pineal gland to the cerebrospinal fluid.

PubMed

Tricoire, Hélène; Malpaux, Benoit; Møller, Morten

2003-01-27

In the sheep, the pineal hormone melatonin displays nocturnal levels 20 times as high in the cerebrospinal fluid of the third ventricle as in the jugular blood. Moreover, in the pineal recess, the evagination of the third ventricle into the pineal stalk, the levels of melatonin in the cerebrospinal fluid are even higher than in the ventral part of the third ventricle. This finding suggests melatonin to be secreted directly from the pineal gland to the ventricular lumen of the pineal recess of this species. We have, therefore, studied the interface between the sheep pineal gland and the cerebrospinal fluid by light-, scanning-, and electron microscopy of the pineal recess, as well as the permeability of the interface by tracer injections into the third ventricle. First, we show that the classic ependymal lining of the third ventricle disappears in the superior part of the recess. In this area, bulging pinealocytes, displaying immunoreactivity for serotonin, directly appose the cerebrospinal fluid. This pineal-cerebrospinal fluid interface of the sheep is large compared with other species, especially rodent species. Intraventricular injections of horseradish peroxidase and fluorescein isothiocyanate showed that both these tracers could permeate from the pineal recess into the sheep pineal parenchyma. This permeation was due to the presence of gap and intermediate junctions connecting the pinealocytes apposing the ventricular lumen. Thus, our results show that endocrine cells in this specialized area of the ventricular system are in direct contact with the cerebrospinal fluid. This finding supports the physiological concept of a direct secretion of melatonin into the cerebrospinal fluid of the sheep pineal recess. Copyright 2002 Wiley-Liss, Inc.

In silico genome wide mining of conserved and novel miRNAs in the brain and pineal gland of Danio rerio using small RNA sequencing data.

PubMed

Agarwal, Suyash; Nagpure, Naresh Sahebrao; Srivastava, Prachi; Kushwaha, Basdeo; Kumar, Ravindra; Pandey, Manmohan; Srivastava, Shreya

2016-03-01

MicroRNAs (miRNAs) are small, non-coding RNA molecules that bind to the mRNA of the target genes and regulate the expression of the gene at the post-transcriptional level. Zebrafish is an economically important freshwater fish species globally considered as a good predictive model for studying human diseases and development. The present study focused on uncovering known as well as novel miRNAs, target prediction of the novel miRNAs and the differential expression of the known miRNA using the small RNA sequencing data of the brain and pineal gland (dark and light treatments) obtained from NCBI SRA. A total of 165, 151 and 145 known zebrafish miRNAs were found in the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Chromosomes 4 and 5 of zebrafish reference assembly GRCz10 were found to contain maximum number of miR genes. The miR-181a and miR-182 were found to be highly expressed in terms of number of reads in the brain and pineal gland, respectively. Other ncRNAs, such as tRNA, rRNA and snoRNA, were curated against Rfam. Using GRCz10 as reference, the subsequent bioinformatic analyses identified 25, 19 and 9 novel miRNAs from the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Targets of the novel miRNAs were identified, based on sequence complementarity between miRNAs and mRNA, by searching for antisense hits in the 3'-UTR of reference RNA sequences of the zebrafish. The discovery of novel miRNAs and their targets in the zebrafish genome can be a valuable scientific resource for further functional studies not only in zebrafish but also in other economically important fishes.

The Pineal and Photoperiodism in Artic Species,

DTIC Science & Technology

1977-01-01

University of Iowa, Iowa City, Iowa *1 A chapter in the book: The Pineal Gland and Reproduction / ::. . / .. ,, " /-. ., . / >( JUN19 1981 A and sale; . td...Three Kinds of Bird Pineal Glands Arctic Mammals and Photoperiod Outline of Arctic Reproductive Physiology Arctic Pineal Physiology: Size Arctic... pineal physiology. Because this gland is not only associated with photoperiodic responses with some species, but also with resistance to cold (14; 21

Biosynthesis and biological action of pineal allopregnanolone

PubMed Central

Tsutsui, Kazuyoshi; Haraguchi, Shogo

2014-01-01

The pineal gland transduces photoperiodic changes to the neuroendocrine system by rhythmic secretion of melatonin. We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Notably, allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It thus appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development. This paper highlights new aspects of the biosynthesis and biological action of pineal allopregnanolone. PMID:24834027

Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland.

PubMed

Piesiewicz, Aneta; Kedzierska, Urszula; Turkowska, Elzbieta; Adamska, Iwona; Majewski, Pawel M

2015-02-01

Previously, we have demonstrated the postembryonic development of chicken (Gallus gallus domesticus L.) pineal gland functions expressed as changes in melatonin (MEL) biosynthesis. Pineal concentrations of MEL and its precursor serotonin (5-HT) were shown to increase between the 2nd and 16th day of life. We also found that levels of the mRNAs encoding the enzymes participating in the final two steps of MEL biosynthesis from 5-HT: arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as their enzymatic activities, were raised during postembryonic development. Moreover, the manner of these changes was season-of-hatch dependent, even in animals kept under constant laboratory conditions (L:D 12:12). The most pronounced changes were seen in the concentrations of 5-HT and MEL, as well as in Aanat mRNA level and its enzymatic activity. The high daily variability in 5-HT content suggested that season- and age-dependent changes in the activity of the chicken pineal gland might rely on the availability of 5-HT, i.e. it may be limited by changes in pineal tryptophan (TRP) and/or 5-hydroxytryptophan (5-HTP) levels as well as by the activity of tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC): two enzymes participating in the conversion of TRP to 5-HT. The present study was undertaken with the following objectives: (1) to examine whether the pineal concentration of the 5-HT precursors TRP and 5-HTP exhibit age- and season-related changes; (2) to look for season-related differences in the transcription of the Tph1 and Ddc genes encoding enzymes TPH and AADC; (3) to identify the step(s) in postembryonic development in which these season-related variations in pineal gland function are most pronounced. Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held in L:D 16:8 conditions were kept from the day of hatch in L:D 12:12 conditions. At the age of 2 or 9 days, animals were sacrificed every 2 or 4 h over a 24-h period and their pineal glands were isolated under dim red light and processed for the measurement of (i) the pineal content of TRP, 5-HTP and 5-HT, and (ii) the level of Tph1 and Ddc mRNAs. Circadian rhythmicity of all the measured parameters was evaluated by the cosinor method. The pineal levels of TRP and 5-HT as well as the Tph1 and Ddc transcripts changed during postembryonic development in a season-related way. Whereas, the 5-HTP concentration did not vary between animals from both age groups, regardless of the season. Circadian rhythmicity of all the measured parameters was dependent on both the age and the season of hatch, and was greatest in older animals in the summer. These findings indicated that the efficiency of season-related MEL biosynthesis, reported previously, is limited by 5-HT availability and this limitation depends on the transcription of both the Tph1 and Ddc genes. Moreover, Ddc mRNA level in 9-d-old birds changed rhythmically, even though this gene is generally considered to be arrhythmic.

Connexin36 localization to pinealocytes in the pineal gland of mouse and rat.

PubMed

Wang, S G; Tsao, D D; Vanderpool, K G; Yasumura, T; Rash, J E; Nagy, J I

2017-06-01

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. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

An autopsy case of sudden unexpected death due to a glial cyst of the pineal gland.

PubMed

Na, Joo-Young; Lee, Kyung-Hwa; Kim, Hyung-Seok; Park, Jong-Tae

2014-09-01

Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms such as chronic headache, paroxysmal headache with gaze paresis, postural syncope, loss of consciousness, and sudden death. A 30-year-old woman with no specific medical history except chronic headache was found collapsed in a public toilet per se. Postmortem examination revealed no external injuries or internal diseases except a cystic lesion of the pineal gland. Histologic examination showed an internal cyst surrounded by glial tissues and pineal parenchyma that was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst cannot be confirmed as the cause of death, it was considered, as no other cause was evident. Herein, we report a pineal cyst considered as an assumed cause of death.

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

PubMed

Cho, Zang-Hee; Choi, Sang-Han; Chi, Je-Gun; Kim, Young-Bo

2011-10-01

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. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Crx broadly modulates the pineal transcriptome

PubMed Central

Rovsing, Louise; Clokie, Samuel; Bustos, Diego M.; Rohde, Kristian; Coon, Steven L.; Litman, Thomas; Rath, Martin F.; Møller, Morten; Klein, David C.

2011-01-01

Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. Here, 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 downregulation of 543 genes and a >2-fold upregulation of 745 genes (p < 0.05). Of these, one of the most highly upregulated (18-fold) is Hoxc4, a member of the Hox gene family, members of which are known to control gene expression cascades. During a 24-hour 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 exhibit differential night/day expression that is 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 upregulation. PMID:21797868

Cytologic features of the normal pineal gland on squash preparations.

PubMed

Murro, Diana; Alsadi, Alaa; Nag, Sukriti; Arvanitis, Leonidas; Gattuso, Paolo

2014-11-01

As primary pineal lesions are extremely rare, many surgical pathologists are unfamiliar with normal pineal cytologic features. We describe cytologic features of the normal pineal gland in patients of varying ages and identify common diagnostic pitfalls. We performed a retrospective review of pineal gland biopsies performed at our institution, where approximately 30,000 surgical specimens are accessioned yearly, for the last 23 years. Only two pineal gland biopsies were found. Although both cases were initially diagnosed as low-grade gliomas on frozen section, the final diagnosis was benign pineal tissue based on light microscopy and immunohistochemistry results. Additionally, we performed squash preparations of five normal pineal gland autopsy specimens with Papanicolaou and Diff-Quik® (Dade Behring, Newark, DE) stains. Infant preparations were highly cellular smears composed of numerous, uniform, single cells with indistinct cytoplasm, small round-to-oval nuclei, fine chromatin, and absent nucleoli and calcifications. The vague microfollicular pattern mimicked a pineocytoma and the fine fibrillary background mimicked a glial neoplasm. Young adult smears were similar; however, microcalcifications were present with fewer background single cells. Older patients had much less cellular smears composed of small clusters of cells with fusiform-to-spindle nuclei, a fine chromatin pattern, and indistinct cytoplasmic borders. There were fewer background single cells and more microcalcifications. The cytologic features of the native pineal gland vary with age. Normal pineal tissue can be confused with a pineocytoma or low-grade glioma. Familiarity with normal pineal gland cytological features will help to avoid a potential misdiagnosis. © 2014 Wiley Periodicals, Inc.

Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men.

PubMed

Sigurdardottir, Lara G; Markt, Sarah C; Sigurdsson, Sigurdur; Aspelund, Thor; Fall, Katja; Schernhammer, Eva; Rider, Jennifer R; Launer, Lenore; Harris, Tamara; Stampfer, Meir J; Gudnason, Vilmundur; Czeisler, Charles A; Lockley, Steven W; Valdimarsdottir, Unnur A; Mucci, Lorelei A

2016-10-01

The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies. © 2016 The Author(s).

Pineal Gland Volume Assessed by MRI and its Correlation with 6-Sulfatoxymelatonin Levels among Older Men

PubMed Central

Sigurdardottir, Lara G.; Markt, Sarah C.; Sigurdsson, Sigurdur; Aspelund, Thor; Fall, Katja; Schernhammer, Eva; Rider, Jennifer R.; Launer, Lenore; Harris, Tamara; Stampfer, Meir J.; Gudnason, Vilmundur; Czeisler, Charles A.; Lockley, Steven W.; Valdimarsdottir, Unnur A.; Mucci, Lorelei A.

2017-01-01

The pineal gland produces the hormone melatonin and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of MR images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm3 (range 65–536 mm3) and parenchyma volume 178 mm3 (range 65–503 mm3). In multivariable-adjusted models pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β=0.52, p<0.001). 6-sulfatoxymelatonin levels did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies. PMID:27449477

Age-related incidence of pineal calcification detected by computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zimmerman, R.A.; Bilaniuk, L.T.

The age-related incidence of detectable pineal calcification in 725 patients (age range, newborn-20 yrs) suggests that there is a relationship between calcification and the hormonal role played by the pineal gland in the regulation of sexual development. Pineal calcification (demonstrated by computed tomography (CT) on 8-mm-thick sections) in patients less than 6 years old should be looked upon with suspicion, and follow-up CT should be considered to exclude the possible development of a pineal neoplasm.

Homeobox genes and melatonin synthesis: regulatory roles of the cone-rod homeobox transcription factor in the rodent pineal gland.

PubMed

Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

2014-01-01

Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

PubMed Central

Rath, Martin Fredensborg

2014-01-01

Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production. PMID:24877149

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator.

PubMed

Ibañez Rodriguez, María P; Noctor, Stephen C; Muñoz, Estela M

2016-01-01

The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. We applied systematic double, triple and quadruple labeling of cell-specific markers on prenatal, postnatal and mature rat pineal gland tissue combined with confocal microscopy to provide a comprehensive view of the cellular dynamics and cell lineages that contribute to pineal gland development. The pineal gland begins as an evagination of neuroepithelium in the roof of the third ventricle. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of Pax6+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers.

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator

PubMed Central

Ibañez Rodriguez, María P.

2016-01-01

The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. We applied systematic double, triple and quadruple labeling of cell-specific markers on prenatal, postnatal and mature rat pineal gland tissue combined with confocal microscopy to provide a comprehensive view of the cellular dynamics and cell lineages that contribute to pineal gland development. The pineal gland begins as an evagination of neuroepithelium in the roof of the third ventricle. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of Pax6+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers. PMID:27861587

Magnetic resonance imaging based morphologic evaluation of the pineal gland for suspected pineoblastoma in retinoblastoma patients and age-matched controls.

PubMed

Pham, Thi Thai Hien; Siebert, Eberhard; Asbach, Patrick; Willerding, Gregor; Erb-Eigner, Katharina

2015-12-15

The purpose of this study was to evaluate the morphologic magnetic resonance imaging (MRI) characteristics of the pineal gland in retinoblastoma (Rb) patients without and with pineoblastoma in comparison to age-matched controls to improve early identification of pineoblastomas (trilateral retinoblastoma, TRb). 80 patients with retinoblastoma and 80 age-matched controls who had undergone brain MRI were included in this retrospective institutional review board approved cohort study. Two readers analyzed the following MR characteristics of the pineal gland: signal intensity on T1- and T2-weighted images, enhancement pattern, delineation of the gland, presence of cystic component, size of pineal gland and size of pineal cysts, respectively. A third reader assessed all images for the presence or absence of pineoblastoma. 3 patients were positive (TRb cohort) and 77 negative for pineoblastoma (non-TRb cohort). The mean maximum diameter of the pineal gland was 6.4mm in Rb patients and 6.3mm in age-matched controls. The mean volume of the pineal gland in Rb patients was 93.1mm(3) and was 87.6mm(3) in age-matched controls. Considering all available MRI scans the mean maximum diameter of the pineal gland in TRb patients was 11.2mm and the mean volume in TRb patients was 453.3mm(3). The third reader identified pineoblastomas with a sensitivity of 100% (3 of 3) and a specificity of 94% (72 of 77). Our non-TRb patients did not show significant differences in the size of the pineal gland and pineal gland cysts compared to age-matched controls. The presented data can serve as a reference for the volume of normal pineal glands and pineal cysts in the diagnostic work-up of Rb patients with suspected pineoblastoma. Copyright © 2015 Elsevier B.V. All rights reserved.

The ontogenic expressions of multiple vesicular glutamate transporters during postnatal development of rat pineal gland.

PubMed

Yoshida, S; Ina, A; Konno, J; Wu, T; Shutoh, F; Nogami, H; Hisano, S

2008-03-18

The pineal gland expresses vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2), which are thought to transport glutamate into synaptic-like microvesicles in the pinealocytes. Recently, we reported that the rat pineal gland also expresses VGLUT1v which is a novel variant of VGLUT1 during the perinatal period. To explore the biological significance of these VGLUT expressions in pineal development, we studied the ontogeny of VGLUT in this gland by in situ hybridization, immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-PCR) using rats. Histological analysis revealed that intensities of VGLUT1 hybridization signal and immunostaining drastically increase by postnatal day (P) 7, whereas VGLUT2 expression exhibits high levels of mRNA and protein at birth and decreases gradually from P7 onward. Quantitative RT-PCR analysis supported these histological observations, showing that expressions of VGLUT1 and VGLUT2 exhibit opposite patterns to each other. Coinciding with VGLUT1-upregulation, RT-PCR data showed that expressions of dynamin 1 and endophilin 1, which are factors predictably involved in the endocytotic recovery of VGLUT1-associated vesicle, are also increased by P7. Quantitative RT-PCR analysis of VGLUT1v demonstrated that its mRNA expression is upregulated by P7, kept at the same level until P14, and apparently decreased at P21, suggesting its functional property required for a certain developmental event. Moreover, a comparison of mRNA expressions at daytime and nighttime revealed that neither VGLUT1 nor VGLUT1v shows any difference in both P7 and P21 glands, whereas VGLUT2 is significantly lower at daytime than at nighttime at P21 but not P7, the time point at which the melatonin rhythm is not yet generated. The present study shows that expressions of these VGLUT types are differentially regulated during postnatal pineal development, each presumably participating in physiologically distinct glutamatergic functions.

Chronic exposure to ELF fields may induce depression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, B.W.

Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pinealmore » gland, giving rise to what may be termed functional pinealectomy. If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders. 85 references.« less

Peptides and Ageing.

PubMed

Khavinson, Vladimir Kh

2002-01-01

A technology has been developed for manufacturing of biologically active complex peptide preparations from extracts of different tissues. In particular, the pineal preparation (Epithalamin) augments the in vitro outgrowth of explants from the pineal gland but not from other tissues, the latter being stimulated by peptide preparations from respective tissues. Epithalamin increases melatonin production by the pineal gland of rats, improves immunological parameters in rats and mice, produces anticarcinogenic effects in different experimental models, stimulates antioxidant defenses, and restores the reproductive function in old rats. These effects are combined in the ability of Epithalamin to increase the lifespan in rats, mice, and fruit flies. Many of these effects are reproduced in clinical trials, which have demonstrated the geroprotector activity of Epithalamin in humans. Among the effects of the thymic preparation Thymalin, those related to its ability to stimulate immunity are the most prominent. This ability is associated with anticarcinogenic and geroprotector activities. Clinical trials of the peptide preparations obtained from other organs including the prostate, the cerebral cortex, and the eye retina, have demonstrated beneficial effects reflected by the improvement of the conditions of respective organs. Based on the data about the amino acid compositions of the peptide preparations, novel principles of the design of biologically active short peptides possessing tissue-specific activities has been developed. Dipeptides specific for the thymus and tetrapeptides specific for the heart, liver, brain cortex, and pineal glands stimulate the in vitro outgrowth of explants of respective organs. Interestingly, for eye retina and the pineal gland, a common tetrapeptide Ala-Glu-Asp-Gly (Epitalon) has been designed, probably reflecting the common embryonal origin of these two organs. Epitalon reproduces the effects of Epithalamin including those related to its geroprotector activity. In particular, Epitalon increases the lifespan of mice and fruit flies and restores the circadian rhythms of melatonin and cortisol production in old rhesus monkeys. At the same time, Epitalon prolongs the functional integrity of the eye retina in Campbell rats with hereditary Retinitis Pigmentosa and improves the visual functions in patients with pigmental retinal degeneration. Changes in gene expression were observed to be produced by the short peptide preparations. Therefore, the effects of Epitalon are suggested to be mediated by transcriptional machinery common for the pineal gland and the retina and, probably, for regulation of melatonin production in fruit flies. Based on three decades of studies of the peptide preparations, the peptide theory of ageing has been put forward. According this theory, ageing is an evolutionary determined biological process of changes in gene expression resulting in impaired synthesis of regulatory and tissue-specific peptides in organs and tissues, which provokes their structural and functional changes and the development of diseases. Correspondingly, correction of such disorders by means of stimulation of peptide production in the organism or through their delivery can promote the normalisation of disturbed body functions.

Regulation of melatonin secretion in the pineal organ of the domestic duck--an in vitro study.

PubMed

Prusik, M; Lewczuk, B; Ziółkowska, N; Przybylska-Gornowicz, B

2015-01-01

The aim of study was to determine the mechanisms regulating melatonin secretion in the pineal organs of 1-day-old and 9-month-old domestic ducks. The pineals were cultured in a superfusion system under different light conditions. Additionally, some explants were treated with norepinephrine. The pineal glands of 1-day-old ducks released melatonin in a well-entrained, regular rhythm during incubation under a 12 hrs light:12 hrs dark cycle and adjusted their secretory activity to a reversed 12 hrs dark:12 hrs light cycle within 2 days. In contrast, the diurnal changes in melatonin secretion from the pineals of 9-month-old ducks were largely irregular and the adaptation to a reversed cycle lasted 3 days. The pineal organs of nestling and adult ducks incubated in a continuous light or darkness secreted melatonin in a circadian rhythm. The treatment with norepinephrine during photophases of a light-dark cycle resulted in: 1) a precise adjustment of melatonin secretion rhythm to the presence of this catecholamine in the culture medium, 2) a very high amplitude of the rhythm, 3) a rapid adaptation of the pineal secretory activity to a reversed light-dark cycle. The effects of norepinephrine were similar in the pineal organs of nestlings and adults. In conclusion, melatonin secretion in the duck pineal organ is controlled by three main mechanisms: the direct photoreception, the endogenous generator and the noradrenergic transmission. The efficiency of intra-pineal, photosensitivity-based regulatory mechanism is markedly lower in adult than in nestling individuals.

The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.

PubMed

Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F

2015-01-01

Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.

The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus

PubMed Central

Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J.; Zykovich, Artem; Coon, Steven L.; Klein, David C.; Rath, Martin F.

2014-01-01

Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9−/− mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9−/− mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9−/− mice at 5–8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9−/−mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus. PMID:24647753

Developmental and diurnal expression of the synaptosomal-associated protein 25 (Snap25) in the rat pineal gland.

PubMed

Karlsen, Anna S; Rath, Martin F; Rohde, Kristian; Toft, Trine; Møller, Morten

2013-06-01

Snap25 (synaptosomal-associated protein) is a 25 kDa protein, belonging to the SNARE-family (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) of proteins, essential for synaptic and secretory vesicle exocytosis. Snap25 has by immunohistochemistry been demonstrated in the rat pineal gland but the biological importance of this is unknown. In this study, we demonstrate a high expression of mRNA encoding Snap25 in all parts of the rat pineal complex, the superficial-, and deep-pineal gland, as well as in the pineal stalk. Snap25 showed a low pineal expression during embryonic stages with a strong increase in expression levels just after birth. The expression showed no day/night variations. Neither removal of the sympathetic input to the pineal gland by superior cervical ganglionectomy nor bilateral decentralization of the superior cervical ganglia significantly affected the expression of Snap25 in the gland. The pineal expression levels of Snap25 were not changed following intraperitoneal injection of isoproterenol. The strong expression of Snap25 in the pineal gland suggests the presence of secretory granules and microvesicles in the rat pinealocyte supporting the concept of a vesicular release. At the transcriptional level, this Snap25-based release mechanism does not exhibit any diurnal rhythmicity and is regulated independently of the sympathetic nervous input to the gland.

Clinical management of pineal cysts: a worldwide online survey.

PubMed

Májovský, Martin; Netuka, David; Beneš, Vladimír

2016-04-01

A pineal cyst is a benign affection of a pineal gland on the borderline between a pathological lesion and a variant of normality. Clinical management of patients with a pineal cyst remains controversial, especially when patients present with non-specific symptoms. An online questionnaire consisting of 13 questions was completed by 110 neurosurgeons worldwide. Responses were entered into a database and subsequently analysed. Based on data from the questionnaire, the main indication criteria for pineal cyst resection are hydrocephalus (90 % of the respondents), Parinaud's syndrome (80 %) and growth of the cyst (68 %). Only 15 % of the respondents occasionally operate on patients with non-specific symptoms. If surgery is indicated, improvement is expected in 88 % of the patients. The vast majority of the respondents favour a supracerebellar infratentorial approach to the pineal region. Most (78 %) of the respondents regarded the patient registry as a potentially useful instrument. This survey sheds light on the current practice of pineal cyst management across the world. Most of the respondents perform surgery on pineal cysts only if patients are presenting with symptoms attributable to a mass effect. Surgery for patients with non-specific complaints (headache, vertigo) is not widely accepted, although it may prove effective. A prospective patient registry might be useful in the decision-making process in the clinical management of pineal cysts.

[Monoamine oxidase activity in rat pineal gland: comparison with brain areas, alteration during aging].

PubMed

Razygraev, A V; Taborskaya, K I; Volovik, K Yu; Bunina, A A; Petrosyan, M A

Using benzylamine as a substrate, the amine oxidase activity was determined in the pineal gland of adult rats and compared with the same activity in brain areas and pituitary. Two groups of rats aged 6-8 and 14-15 months were also compared on the basis of this activity. Benzylamine deaminating activity in the pineal gland was significantly higher than in the area preoptica medialis, the corpus mamillare, the tuberculum olfactorium, and the hypophysis, and lower than in the eminentia mediana. The significant increase of the activity in the pineal gland in animals of age from 6-8 to 14-15-months was revealed. Benzylamine deaminating activity in the pineal gland was totally inhibited by 0,002 mM R deprenyl, indicating the B type monoamine oxidase (MAO B) activity. Age-associated increase of MAO B activity in the pineal gland accompanied by decrease of glutathione peroxidase activity, reported earlier, can promote the oxidative damage in the pineal gland during aging.

Atypical pleomorphic neoplasms of the pineal gland: Case report and review of the literature.

PubMed

Praver, M; D'Amico, R; Arraez, C; Zacharia, B E; Varma, H; Goldman, J E; Bruce, J N; Canoll, P

2015-01-01

Pineal region tumors are rare and diverse. Among them exist reports of pleomorphic xanthroastrocytoma (PXA) and pleomorphic granular cell astrocytoma (PGCA) of the pineal gland. These related tumors are remarkably similar sharing pleomorphic histologic features with only minor immunohistochemical and ultrastructural differences. We present a case of a 42-year old right-handed woman presented with a longstanding history of migraine headaches which had worsened over the two months leading up to her hospitalization. MRI revealed a 1.7 × 1.3 × 1.6 cm intensely enhancing lesion originating in the pineal gland. The tumor closely resembled PGCA but did not strictly fit the diagnostic requirements of either PGCA or PXA. The present case highlights the exotic nature of pineal region tumors with pleomorphic cell histology. Given the diverse range of tumors encountered in the pineal region, pathological confirmation is mandatory. Favorable clinical outcomes demonstrate that surgical resection alone can yield excellent long-term results for tumors falling within the spectrum of pleomorphic lesions of the pineal gland.

GABAergic signaling in the rat pineal gland.

PubMed

Yu, Haijie; Benitez, Sergio G; Jung, Seung-Ryoung; Farias Altamirano, Luz E; Kruse, Martin; Seo, Jong Bae; Koh, Duk-Su; Muñoz, Estela M; Hille, Bertil

2016-08-01

Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here, we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB 1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca(2+) channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48-72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus, strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New Prophylactic and Therapeutic Strategies for Spinal Cord Injury.

PubMed

Park, Sookyoung; Park, Kanghui; Lee, Youngjeon; Chang, Kyu-Tae; Hong, Yonggeun

2013-03-01

Melatonin production by the pineal gland in the vertebrate brain has attracted much scientific attention. Pineal melatonin is regulated by photoperiodicity, whereas circadian secretion of melatonin produced in the gastrointestinal tract is regulated by food intake. Thus, the circadian rhythm of pineal melatonin depends upon whether a species is diurnal or nocturnal. Spinal cord injury (SCI) involves damage to the spinal cord caused by trauma or disease that results in compromise or loss of body function. Melatonin is the most efficient and commonly used pharmacological antioxidant treatment for SCI. Melatonin is an indolamine secreted by the pineal gland during the dark phase of the circadian cycle. Neurorehabilitation is a complex medical process that focuses on improving function and repairing damaged connections in the brain and nervous system following injury. Physical activity associated with an active lifestyle reduces the risk of obesity, cardiovascular disease, type 2 diabetes, osteoporosis, and depression and protects against neurological conditions, including Parkinson's disease, Alzheimer's disease, and ischemic stroke. Physical activity has been shown to increase the gene expression of several brain neurotrophins (brain-derived neurotrophic factor [BDNF], nerve growth factor, and galanin) and the production of mitochondrial uncoupling protein 2, which promotes neuronal survival, differentiation, and growth. In summary, melatonin is a neural protectant, and when combined with therapeutic exercise, the hormone prevents the progression of secondary neuronal degeneration in SCI. The present review briefly describes the pathophysiological mechanisms underlying SCI, focusing on therapeutic targets and combined melatonin and exercise therapy, which can attenuate secondary injury mechanisms with minimal side effects.

GABAergic signaling in the rat pineal gland

PubMed Central

Yu, Haijie; Benitez, Sergio G.; Jung, Seung-Ryoung; Farias Altamirano, Luz E.; Kruse, Martin; Seo, Jong-Bae; Koh, Duk-Su; Muñoz, Estela M.; Hille, Bertil

2017-01-01

Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic enzyme GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca2+ channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48–72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found. PMID:27019076

Beyond the pineal gland assumption: a neuroanatomical appraisal of dualism in Descartes' philosophy.

PubMed

Berhouma, Moncef

2013-09-01

The problem of the substantial union of the soul and the body and therefore the mechanisms of interaction between them represents the core of the Cartesian dualistic philosophy. This philosophy is based upon a neuroanatomical obvious misconception, consisting mainly on a wrong intraventricular position of the pineal gland and its capacity of movement to act as a valve regulating the flow of animal spirits. Should we consider the Cartesian neurophysiology as a purely anatomical descriptive work and therefore totally incorrect, or rather as a theoretical conception supporting his dualistic philosophy? From the various pre-Cartesian theories on the pineal organ, we try to explain how Descartes used his original conception of neuroanatomy to serve his dualistic philosophy. Moreover, we present an appraisal of the Cartesian neuroanatomical corpus from an anatomical but also metaphysical and theological perspectives. A new interpretation of Descartes' writings and an analysis of the secondary related literature shed the light on the voluntary anatomical approximations aiming to build an ad hoc neurophysiology that allows Descartes' soul-body theory. By its central position within the brain mass and its particular shape, the pineal gland raised diverse metaphysical theories regarding its function, but the most original theory remains certainly its role as the seat of soul in René Descartes' philosophy and more precisely the organ where soul and body interact. The author emphasizes on the critics raised by Descartes' theories on the soul-body interaction through the role of the pineal gland. Copyright © 2013 Elsevier B.V. All rights reserved.

Light-Emitting Diodes and Cool White Fluorescent Light Similarly Suppress Pineal Gland Melatonin and Maintain Retinal Function and Morphology in the Rat. Part 1

NASA Technical Reports Server (NTRS)

Holley, Daniel C.; Heeke, D.; Mele, G.

1999-01-01

Currently, the light sources most commonly used in animal habitat lighting are cool white fluorescent or incandescent lamps. We evaluated a novel light-emitting diode (LED) light source for use in animal habitat lighting by comparing its effectiveness to cool white fluorescent light (CWF) in suppressing pineal gland melatonin and maintaining normal retinal physiology and morphology in the rat. Results of pineal melatonin suppression experiments showed equal suppression of pineal melatonin concentrations for LED light and CWF light at five different light illuminances (100, 40, 10, 1 and 0.1 lux). There were no significant differences in melatonin suppression between LED and CWF light when compared to unexposed controls. Retinal physiology was evaluated using electroretinography. Results show no differences in a-wave implicit times and amplitudes or b-wave implicit times and amplitudes between 100-lux LED-exposed rats and 100-lux CWF-exposed rats. Results of retinal histology assessment show no differences in retinal thickness rod outer segment length and number of rod nuclei between rats exposed to 100-lux LED and 100-lux CWF for days. Furthermore, the retinal pigmented epithelium and rod outer segments of all eyes observed were in good condition and of normal thickness. This study indicates that LED light does not cause retinal damage and can suppress pineal melatonin at similar intensities as a conventional CWF light source. These data suggest that LED light sources may be suitable replacements for conventional light sources used in the lighting of rodent vivariums while providing many mechanical and economical advantages.

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.

PubMed Central

Holmes, E. W.; Hojvat, S. A.; Kahn, S. E.; Bermes, E. W.

1989-01-01

Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents of PNx rats were decreased to approximately 60% of the control value (P less than 0.05). There were no differences in plasma prolactin levels between the control and PNx groups either at mid-day or in the middle of the night. Nocturnal pineal NAT activity in PNx rats was markedly reduced to approximately 20% of the control value (P less than 0.001). Similar evidence of gonadal dysfunction (reduced plasma total testosterone and testes testosterone content) and a significant decrease in night-time levels of pineal NAT activity were also observed after 13 weeks of CRI in PNx rats of the Sprague-Dawley strain that were housed under a different photoperiod. These results suggest that pineal gland dysfunction is a feature of CRI in the PNx model. Such an abnormality might contribute to the pathogenesis of gonadal dysfunction in CRI. PMID:2765391

Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creighton, J.A.; Rudeen, P.K.

The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effectmore » upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity.« less

TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway.

PubMed

da Silveira Cruz-Machado, Sanseray; Carvalho-Sousa, Claudia Emanuele; Tamura, Eduardo Koji; Pinato, Luciana; Cecon, Erika; Fernandes, Pedro Augusto Carlos Magno; de Avellar, Maria Christina Werneck; Ferreira, Zulma Silva; Markus, Regina Pekelmann

2010-09-01

Nuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N-acetylserotonin in cultured glands. The reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram-negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. The maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. In addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response.

Animal Models of Jet Lag

DTIC Science & Technology

2012-01-20

surgically inserted into the pineal gland and connected to a peristaltic pump that delivers saline solution at low rate and to a outlet tubing that delivers...Journal of Pineal Research. 48(3):290- 6,2010. 2. "Orcadian Regulation of Pineal Gland Rhythmicity", Jimo Borjigin, L. Samantha Zhang, Anda-Alexandra...specializes in the longitudinal monitoring of pineal melatonin secretion for weeks at a time to decipher mechanisms of circadian pacemaker entrainment

Pineal region tumors: computed tomographic-pathologic spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Futrell, N.N.; Osborn, A.G.; Cheson. B.D.

While several computed tomographic (CT) studies of posterior third ventricular neoplasms have included descriptions of pineal tumors, few reports have concentrated on these uncommon lesions. Some authors have asserted that the CT appearance of many pineal tumors is virtually pathognomonic. A series of nine biopsy-proved pineal gland and eight other presumed tumors is presented that illustrates their remarkable heterogeneity in both histopathologic and CT appearance. These tumors included germinomas, teratocarcinomas, hamartomas, and other varieties. They had variable margination, attentuation, calcification, and suprasellar extension. Germinomas have the best response to radiation therapy. Biopsy of pineal region tumors is now feasible andmore » is recommended for treatment planning.« less

Is there a correlation between the pineal gland calcification and migraine?

PubMed

Ozlece, H K; Akyuz, O; Ilik, F; Huseyinoglu, N; Aydin, S; Can, S; Serim, V A

2015-10-01

The pineal gland calcifications have been associated with some diseases such as cerebral infarction, Alzheimer's disease and intracerebral hemorrhage while most cases are considered idiopathic and physiologic. However, there are limited data in the current literature about the association of pineal calcification and migraine. Our aim was to evaluate this association between migraine and pineal calcification by computed tomography of the brain. In our study, we assessed the computed tomography images of patients, who referred to the neurology outpatient clinic with the complaint of headache and were diagnosed with migraine without aura based according to 2004 criteria of the International Headache Society. 503 migraine patients and 500 control subjects without migraine diagnosis were included in this study. When migraine and control groups were compared by pineal calcification, the rates were determined as 80, 6% and 55% in migraine and control group, respectively. The difference was statistically significant (p < 0.001). In addition, it was seen that pineal calcifications, detected in migraine patients, did not show age-related increase. According to our data, we can point that pineal calcification may be associated with migraine.

Pineal organs of deep-sea fish: photopigments and structure.

PubMed

Bowmaker, James K; Wagner, Hans-Joachim

2004-06-01

We have examined the morphology and photopigments of the pineal organs from a number of mesopelagic fish, including representatives of the hatchet fish (Sternoptychidae), scaly dragon-fish (Chauliodontidae) and bristlemouths (Gonostomidae). Although these fish were caught at depths of between 500 and 1000 m, the morphological organisation of their pineal organs is remarkably similar to that of surface-dwelling fish. Photoreceptor inner and outer segments protrude into the lumen of the pineal vesicle, and the outer segment is composed of a stack of up to 20 curved disks that form a cap-like cover over the inner segment. In all species, the pineal photopigment was spectrally distinct from the retinal rod pigment, with lambdamax displaced to longer wavelengths, between approximately 485 and 503 nm. We also investigated the pineal organ of the deep demersal eel, Synaphobranchus kaupi, caught at depths below 2000 m, which possesses a rod visual pigment with lambdamax at 478 nm, but the pineal pigment has lambdamax at approximately 515 nm. In one species of hatchet fish, Argyropelecus affinis, two spectral classes of pinealocyte were identified, both spectrally distinct from the retinal rod photopigment.

A new identified complication of intracystic hemorrhage in a large pineal gland cyst.

PubMed

Mehrzad, Raman; Mishra, Suprav; Feinstein, Alexander; Ho, Michael G

2014-01-01

Pineal gland cysts are typically asymptomatic, benign cysts most commonly found incidentally in adults. In rare cases, a large pineal gland cyst can be complicated by intracystic hemorrhage, which could then manifest with neurological symptoms. We report a new complication of intracystic hemorrhage in a large pineal gland cyst in a 40-year-old man with new onset seizures. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroendoscopy and pineal tumors: A review of the literature and our considerations regarding its utility.

PubMed

Mottolese, C; Szathamari, A; Beuriat, P A; Grassiot, B; Simon, E

2015-01-01

Endoscopy has entered into the armamentarium of pineal and pineal region tumor treatment. The technique permits not only to control hydrocephalus but also to obtain tissue samples for histological diagnosis. In this paper, we explain the utility of endoscopy for the treatment of pineal tumors and as well as report some personal considerations regarding this topic. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Marked rapid alterations in nocturnal pineal serotonin metabolism in mice and rats exposed to weak intermittent magnetic fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lerchl, A.; Nonaka, K.O.; Stokkan, K.A.

Adult AMES mice and male Sprague Dawley rats were exposed to an artificial magnetic field, generated by Helmholtz coils. 3.5 hours after the onset of darkness the coils were activated for one hour resulting in an inversion of the horizontal component of the earth's magnetic field. The coils were activated and deactivated at 5 min intervals during the 1 hour exposure period. In both mice and rats, the levels of serotonin in the pineal were markedly increased by the exposure. In rats, an increase of pineal 5-hydroxyindole acetic acid and a decrease of the activity of the pineal enzyme serotonin-N-acetyltransferasemore » also was observed. However, pineal and serum melatonin levels were not altered. The results indicate that the metabolism of serotonin in the pineal is quickly affected by the exposure of animals to a magnetic field.« less

Alpha-2 adrenergic activity of bromocriptine and quinpirole in chicken pineal gland. Effects on melatonin synthesis and ( sup 3 H)rauwolscine binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zawilska, J.; Iuvone, P.M.

In the pineal gland and retina of chickens, serotonin N-acetyl-transferase (NAT) activity and melatonin content are modulated by different receptors, alpha-2 adrenergic receptors in pineal gland and D2-dopamine receptors in retina. The effect of two D2-dopamine receptor agonists, bromocriptine and quinpirole (LY 171555), on melatonin synthesis in these tissues was investigated. Systemic administrations of bromocriptine and quinpirole decreased nocturnal NAT activity and melatonin content of both pineal gland and retina. Bromocriptine was equipotent in the two tissues, whereas quinpirole was approximately 100-fold more potent in retina than in pineal gland. In pineal gland, the suppressive effects of bromocriptine and quinpirolemore » on NAT activity were blocked by yohimbine, a selective alpha-2 adrenergic receptor antagonist, but not by spiperone, a D2-dopamine receptor antagonist. In contrast, bromocriptine- and quinpirole-induced decreases of the enzyme activity in retina were antagonized by spiperone, and not affected by yohimbine. The nocturnal increase of NAT activity of pineal glands in vitro was inhibited with an order of potency clonidine greater than bromocriptine greater than quinpirole. Additionally, bromocriptine and quinpirole displaced the specific binding of (3H)rauwolscine, an alpha-2 adrenergic receptor antagonist, to membranes from chicken pineal gland, with potencies comparable to those observed for inhibition of NAT activity in vitro. It is suggested that bromocriptine and quinpirole, in addition to their D2-dopaminergic activity, can stimulate alpha-2 adrenergic receptors in pineal gland of chicken.« less

Annual reproductive synchronization in ovary and pineal gland function of female short-nosed fruit bat, Cynopterus sphinx.

PubMed

Haldar, Chandana; Yadav, Rajesh; Alipreeta

2006-08-01

We studied the annual correlation of ovarian activity and pineal gland in relation with seasonal variation and gestation of a tropical zone short-nosed fruit bat Cynopterus sphinx. Female bats showed bimodal polyestry (February/March and September/October) in their reproductive cycle. Plasma estradiol concentration ran parallel with ovarian activity and had an inverse relation with pineal mass and peripheral melatonin concentration. Due to the delayed embryonic development in the uterus (October-March) of female bats, interestingly, the uterine activity did not show a parallel relation with ovarian activity and estradiol level. Further, compared with normal non-pregnant females, melatonin level was high during gestation and delayed embryonic development phase. This suggests that the reproductive synchrony and annual variation in ovarian activity of this nocturnal flying mammal differ from other common tropical mammals. The delayed embryonic development in bats might be an adaptive strategy for the unfavorable conditions of the seasons and might be regulated by high peripheral estradiol and melatonin concentration.

Reduced Pineal Volume in Alzheimer Disease: A Retrospective Cross-sectional MR Imaging Study.

PubMed

Matsuoka, Teruyuki; Imai, Ayu; Fujimoto, Hiroshi; Kato, Yuka; Shibata, Keisuke; Nakamura, Kaeko; Yokota, Hajime; Yamada, Kei; Narumoto, Jin

2018-01-01

Purpose To evaluate pineal volume in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and healthy control subjects and to correlate the findings with results of cognitive testing and brain parenchymal volumes. Materials and Methods The ethics committee approved this retrospective study. The participants included 63 patients with AD, 33 patients with MCI, and 24 healthy control subjects. There were 36 men and 84 women, with a mean age (±standard deviation) of 76.7 years ± 7.6. The pineal gland volume and pineal parenchymal volume were measured by using three-dimensional volumetric magnetic resonance imaging (T1-weighted magnetization-prepared rapid gradient-echo sequence; spatial resolution, 0.9 × 0.98 × 0.98 mm). With age and total intracranial volume as covariates, analysis of covariance with the Bonferroni post hoc test was performed to compare the pineal volume among the AD, MCI, and control groups. Multiple regression analyses were used to identify predictor variables associated with pineal volume. Results The mean pineal gland volume in patients with AD (72.3 mm 3 ± 5.4; 95% confidence interval [CI]: 61.5 mm 3 , 83.1 mm 3 ) was significantly smaller than that in control subjects (102.1 mm 3 ± 9.0; 95% CI: 84.4 mm 3 , 119.9 mm 3 ) (P = .019). The mean pineal parenchymal volume in patients with AD (63.8 mm 3 ± 4.2; 95% CI: 55.4 mm 3 , 72.1 mm 3 ) was significantly smaller than that in patients with MCI (81.7 mm 3 ± 5.8; 95% CI: 70.3 mm 3 , 93.1 mm 3 ; P = .044) and control subjects (89.1 mm 3 ± 6.9; 95% CI: 75.4 mm 3 , 102.9 mm 3 ; P = .009). Multiple regression analyses demonstrated that the Mini-Mental State Examination score and total intracranial volume were significant independent predictors of both pineal gland volume and pineal parenchymal volume (P < .001). Conclusion Pineal volume reduction showed correlation with cognitive decline and thus might be useful to predict cognitive decline in patients with AD. © RSNA, 2017.

Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratt, B.L.; Takahashi, J.S.

The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxinmore » partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.« less

Light pollution, reproductive function and cancer risk.

PubMed

Anisimov, Vladimir N

2006-01-01

At present, light pollution (exposure to light-at-night) both in the form of occupational exposure during night work and as a personal choice and life style, is experienced by numerous night-active members of our society. Disruption of the circadian rhythms induced by light pollution has been associated with cancer in humans. There are epidemiological evidences of increased breast and colon cancer risk in shift workers. An inhibition of the pineal gland function with exposure to the constant light (LL) regimen promoted carcinogenesis whereas the light deprivation inhibits the carcinogenesis. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the LL regimen. These observations might lead to use melatonin for cancer prevention in groups of humans at risk of light pollution.

Season-dependent effects of photoperiod and temperature on circadian rhythm of arylalkylamine N-acetyltransferase2 gene expression in pineal organ of an air-breathing catfish, Clarias gariepinus.

PubMed

Singh, Kshetrimayum Manisana; Saha, Saurav; Gupta, Braj Bansh Prasad

2017-08-01

Arylalkylamine N-acetyltransferase (AANAT) activity, aanat gene expression and melatonin production have been reported to exhibit prominent circadian rhythm in the pineal organ of most species of fish. Three types of aanat genes are expressed in fish, but the fish pineal organ predominantly expresses aanat2 gene. Increase and decrease in daylength is invariably associated with increase and decrease in temperature, respectively. But so far no attempt has been made to delineate the role of photoperiod and temperature in regulation of the circadian rhythm of aanat2 gene expression in the pineal organ of any fish with special reference to seasons. Therefore, we studied effects of various lighting regimes (12L-12D, 16L-8D, 8L-16D, LL and DD) at a constant temperature (25°C) and effects of different temperatures (15°, 25° and 35°C) under a common photoperiod 12L-12D on circadian rhythm of aanat2 gene expression in the pineal organ of Clarias gariepinus during summer and winter seasons. Aanat2 gene expression in fish pineal organ was studied by measuring aanat2 mRNA levels using Real-Time PCR. Our findings indicate that the pineal organ of C. gariepinus exhibits a prominent circadian rhythm of aanat2 gene expression irrespective of photoperiods, temperatures and seasons, and the circadian rhythm of aanat2 gene expression responds differently to different photoperiods and temperatures in a season-dependent manner. Existence of circadian rhythm of aanat2 gene expression in pineal organs maintained in vitro under 12L-12D and DD conditions as well as a free running rhythm of the gene expression in pineal organ of the fish maintained under LL and DD conditions suggest that the fish pineal organ possesses an endogenous circadian oscillator, which is entrained by light-dark cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence of pineal gland cyst and pineoblastoma in children with retinoblastoma during the chemoreduction era.

PubMed

Ramasubramanian, Aparna; Kytasty, Christina; Meadows, Anna T; Shields, Jerry A; Leahey, Ann; Shields, Carol L

2013-10-01

To report on the frequency of cysts and tumors of the pineal gland in patients with retinoblastoma. Observational retrospective case control study. Institutional. study population: Four hundred eight patients treated for retinoblastoma from January 2000 to January 2012 at Wills Eye Institute, Philadelphia, Pennsylvania, USA. Magnetic resonance imaging (MRI) features of the pineal gland were evaluated in all patients with retinoblastoma. Characteristics of patients with pineal cysts and pineoblastoma were reviewed. Comparison of frequency of pineal gland cyst and pineoblastoma in children managed with systemic chemoreduction vs other methods. Of 408 patients, treatment included systemic chemoreduction in 252 (62%) and nonchemoreduction methods in 156 (38%). Overall, 34 patients (8%) manifested pineal gland cyst and 4 (1%) showed pineoblastoma. Of all 408 patients, comparison (chemoreduction vs nonchemoreduction) revealed pineal cyst (20/252 vs 14/156, P = .7) and pineoblastoma (1/252 vs 3/156, P = .1). The pineal cyst (n = 34) (mean diameter 4 mm) was asymptomatic (n = 34), followed conservatively (n = 34), and with minimal enlargement (n = 2, 9%) but without progression to pineoblastoma. The cyst was found in 22 germline and 12 nongermline patients (P = .15). Among the 4 patients with pineoblastoma, all had germline mutation and 2 had family history of retinoblastoma. Among all patients with family history of retinoblastoma (n = 45), 2 (4%) developed pineoblastoma. The pineoblastoma was asymptomatic in 2 patients and symptomatic with vomiting and headache in 2 patients. The mean interval from date of retinoblastoma detection to pineal cyst was 2 months (median 2, range 0-8 months) and to pineoblastoma was 27 months (median 28, range 7-46 months). Management included aggressive chemotherapy and radiotherapy, with 2 survivors. Pineal gland cyst was incidentally detected in 8% of retinoblastoma patients, causing no symptoms, and without progression to pineoblastoma. Pineoblastoma was detected in 1% of patients and fewer patients who received systemic chemotherapy developed pineoblastoma, possibly indicating a systemic protective effect. Copyright © 2013 Elsevier Inc. All rights reserved.

Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

PubMed

Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

2015-08-01

Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body. © 2015 by The Author(s).

Incidental pineal cysts in children who undergo 3-T MRI.

PubMed

Whitehead, Matthew T; Oh, Christopher C; Choudhri, Asim F

2013-12-01

Pineal cysts, both simple and complex, are commonly encountered in children. More cysts are being detected with MR technology; however, nearly all pineal cysts are benign and require no follow-up. To discover the prevalence of pineal cysts in children at our institution who have undergone high-resolution 3-T MRI. We retrospectively reviewed 100 consecutive 3-T brain MRIs in children ages 1 month to 17 years (mean 6.8 ± 5.1 years). We evaluated 3-D volumetric T1-W imaging, axial T2-W imaging, axial T2-W FLAIR (fluid attenuated inversion recovery) and coronal STIR (short tau inversion recovery) sequences. Pineal parenchymal and cyst volumes were measured in three planes. Cysts were analyzed for the presence and degree of complexity. Pineal cysts were present in 57% of children, with a mean maximum linear dimension of 4.2 mm (range 1.5-16 mm). Of these cysts, 24.6% showed thin septations or fluid levels reflecting complexity. None of the cysts demonstrated complete T2/FLAIR signal suppression. No cyst wall thickening or nodularity was present. There was no significant difference between the ages of children with and without cysts. Cysts were more commonly encountered in girls than boys (67% vs. 52%; P = 0.043). There was a slight trend toward increasing pineal gland volume with age. Pineal cysts are often present in children and can be incidentally detected by 3-T MRI. Characteristic-appearing pineal cysts in children are benign, incidental findings, for which follow-up is not required if there are no referable symptoms or excessive size.

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part I, the solid gland.

PubMed

Galluzzi, Paolo; de Jong, Marcus C; Sirin, Selma; Maeder, Philippe; Piu, Pietro; Cerase, Alfonso; Monti, Lucia; Brisse, Hervé J; Castelijns, Jonas A; de Graaf, Pim; Goericke, Sophia L

2016-07-01

Differentiation between normal solid (non-cystic) pineal glands and pineal pathologies on brain MRI is difficult. The aim of this study was to assess the size of the solid pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. We retrospectively analyzed the size (width, height, planimetric area) of solid pineal glands in 184 non-retinoblastoma patients (73 female, 111 male) aged 0-5 years on MRI. The effect of age and gender on gland size was evaluated. Linear regression analysis was performed to analyze the relation between size and age. Ninety-nine percent prediction intervals around the mean were added to construct a normal size range per age, with the upper bound of the predictive interval as the parameter of interest as a cutoff for normalcy. There was no significant interaction of gender and age for all the three pineal gland parameters (width, height, and area). Linear regression analysis gave 99 % upper prediction bounds of 7.9, 4.8, and 25.4 mm(2), respectively, for width, height, and area. The slopes (size increase per month) of each parameter were 0.046, 0.023, and 0.202, respectively. Ninety-three percent (95 % CI 66-100 %) of asymptomatic solid pineoblastomas were larger in size than the 99 % upper bound. This study establishes norms for solid pineal gland size in non-retinoblastoma children aged 0-5 years. Knowledge of the size of the normal pineal gland is helpful for detection of pineal gland abnormalities, particularly pineoblastoma.

Follow-up of pineal cysts in children: is it necessary?

PubMed

Jussila, Miro-Pekka; Olsén, Päivi; Salokorpi, Niina; Suo-Palosaari, Maria

2017-12-01

Pineal cysts are common incidental findings in children undergoing magnetic resonance imaging (MRI). Several studies have suggested MRI follow-up if the cyst is larger than 10 mm. However, cysts do not usually change during follow-up. Prevalence, growth, and structure of the pineal cysts were analyzed to decide if follow-up MRI is necessary. A retrospective review between 2010 and 2015 was performed using 3851 MRI examinations of children aged 0-16 years to detect pineal cysts having a maximum diameter ≥ 10 mm. Eighty-one children with pineal cysts were identified and 79 of them had been controlled by MRI. Cysts were analyzed for the size, growth, and structure. A total of 1.8% of the children had a pineal cyst with a diameter ≥ 10 mm. Cysts were present in 48 girls (59.3%) and 33 boys (40.7%). Most pineal cysts (70/79) did not significantly grow during the follow-up (median 10 months, range 3-145 months). A total of 11.4% (9/79) of the cysts grew with the biggest change measured from the outer cyst wall sagittal anteroposterior dimension (mean 3.4 mm ± 1.7 mm). Only one cyst grew more than 5 mm. We found no factors correlating with the cyst growth among 9 cysts that grew > 2 mm. A majority of pineal cysts remained unchanged during the MRI follow-up. Results of this study suggest that routine MRI follow-up of pineal cysts is not necessary in the absence of unusual radiological characteristics or related clinical symptoms.

[Regulating effect of pineal gland peptides on development of T-lymphocytes in CBA aging mice: role of microenvironment of immune system organs and neuroendocrine factors].

PubMed

Labunets, I F; Butenko, G M; Khavinson, V Kh; Magdich, L V; Dragunova, V A; Pishel', I N; Azarskova, M V

2003-01-01

Studies were undertaken on the development of T-lymphocytes in adult and old CBA mice and its changes at aging after injections of pineal gland peptides. It was shown that in old mice the disturbances of T-cells differentiation are registered in bone marrow, thymus, spleen and characterized by the changes of lymphocyte markers expression, migration and proliferation of cells. In old mice FTS titer, melatonin and testosterone levels decreased, the balance of noradrenalin and serotonin in hypothalamus and the cell composition of microenvironment immune systems organs impaired. After chronic (18 mo) administration of the pineal gland preparation epithalamin the amount of stromal cells-precursors, CD4+ and Mac-1(+)-cells in old bone marrow increased, improved the migration of T-cell precursors from bone marrow to thymus and their proliferative potential. The proportion of CD3+, CD4+CD8-, CD4-CD8+, Mac-1(+)-cells in old thymus increased, while that of CD44(+)-cells decreased. The proportion of CD4-CD8(+)-cells in spleen increased. The most number of indices and their balance showed a pattern of adult mice. In old mice after epithalamin the balance of amines in hypothalamus improved, concentration of melatonin in pineal gland, testosterone and FTS titer in blood increased. Epithalon has also the possibility to increase of thymic endocrine function.

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.

PubMed

Litvinenko, G I; Shurlygina, A V; Gritsyk, O B; Mel'nikova, E V; Tenditnik, M V; Avrorov, P A; Trufakin, V A

2015-10-01

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.

Pink spot, white spot: the pineal skylight of the leatherback turtle (Dermochelys coriacea Vandelli 1761) skull and its possible role in the phenology of feeding migrations

USGS Publications Warehouse

Davenport, John; Jones, T. Todd; Work, Thierry M.; Balazs, George H.

2014-01-01

Leatherback turtles, Dermochelys coriacea, which have an irregular pink area on the crown of the head known as the pineal or ‘pink spot’, forage upon jellyfish in cool temperate waters along the western and eastern margins of the North Atlantic during the summer. Our study showed that the skeletal structures underlying the pink spot in juvenile and adult turtles are compatible with the idea of a pineal dosimeter function that would support recognition of environmental light stimuli. We interrogated an extensive turtle sightings database to elucidate the phenology of leatherback foraging during summer months around Great Britain and Ireland and compared the sightings with historical data for sea surface temperatures and day lengths to assess whether sea surface temperature or light periodicity/levels were likely abiotic triggers prompting foraging turtles to turn south and leave their feeding grounds at the end of the summer. We found that sea temperature was too variable and slow changing in the study area to be useful as a trigger and suggest that shortening of day lengths as the late summer equilux is approached provides a credible phenological cue, acting via the pineal, for leatherbacks to leave their foraging areas whether they are feeding close to Nova Scotia or Great Britain and Ireland.

Pinealectomy shortens resynchronisation times of house sparrow ( Passer domesticus) circadian rhythms

NASA Astrophysics Data System (ADS)

Kumar, Vinod; Gwinner, Eberhard

2005-09-01

In many birds periodic melatonin secretion by the pineal organ is essential for the high-amplitude self-sustained output of the circadian pacemaker, and thus for the persistence of rhythmicity in 24 h oscillations controlled by it. The elimination of the pineal melatonin rhythm, or a reduction of its amplitude, renders the circadian pacemaker a less self-sustained, often highly damped, oscillatory system. A reduction in the degree of self-sustainment of a rhythm should not only increase its range of entrainment but also shorten the resynchronization times following phase-shifts of the zeitgeber. This hypothesis has not yet been directly tested. We therefore carried out the present study in which house sparrows (Passer domesticus) were subjected to both 6-h advance and 6-h delay phase-shifts of the light-dark cycle before and after the pinealectomy, and the rhythms in locomotion and feeding were recorded. The results indicate that following the delay, but not the advance, phase shift, resynchronization times were significantly shorter after pinealectomy. The dependence of resynchronization times on the presence or absence of the pineal organ is not only of theoretical interest but might also be of functional significance in the natural life of birds. A reduction or elimination of the amplitude of the melatonin secretion rhythm by the pineal organ might be responsible for faster adjustment to changes in zeitgeber conditions in nature.

Post-natal growth in the rat pineal gland: a stereological study.

PubMed

Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E

2012-10-01

The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies. © 2012 Blackwell Verlag GmbH.

Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome

PubMed Central

Hartley, Stephen W.; Coon, Steven L.; Savastano, Luis E.; Mullikin, James C.; Fu, Cong; Klein, David C.

2015-01-01

The term neurotranscriptomics is used here to describe genome-wide analysis of neural control of transcriptomes. In this report, next-generation RNA sequencing was using to analyze the effects of neonatal (5-days-of-age) surgical stimulus deprivation on the adult rat pineal transcriptome. In intact animals, more than 3000 coding genes were found to exhibit differential expression (adjusted-p < 0.001) on a night/day basis in the pineal gland (70% of these increased at night, 376 genes changed more than 4-fold in either direction). Of these, more than two thousand genes were not previously known to be differentially expressed on a night/day basis. The night/day changes in expression were almost completely eliminated by neonatal removal (SCGX) or decentralization (DCN) of the superior cervical ganglia (SCG), which innervate the pineal gland. Other than the loss of rhythmic variation, surgical stimulus deprivation had little impact on the abundance of most genes; of particular interest, expression levels of the melatonin-synthesis-related genes Tph1, Gch1, and Asmt displayed little change (less than 35%) following DCN or SCGX. However, strong and consistent changes were observed in the expression of a small number of genes including the gene encoding Serpina1, a secreted protease inhibitor that might influence extracellular architecture. Many of the genes that exhibited night/day differential expression in intact animals also exhibited similar changes following in vitro treatment with norepinephrine, a superior cervical ganglia transmitter, or with an analog of cyclic AMP, a norepinephrine second messenger in this tissue. These findings are of significance in that they establish that the pineal-defining transcriptome is established prior to the neonatal period. Further, this work expands our knowledge of the biological process under neural control in this tissue and underlines the value of RNA sequencing in revealing how neurotransmission influences cell biology. PMID:26367423

Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas.

PubMed

Goncharova, N D; Vengerin, A A; Khavinson, V Kh; Lapin, B A

2005-01-01

The purpose of this research was to study age-related changes in functioning of pineal and pancreatic glands of non-human primates, rhesus monkeys, and to elucidate the possibility of their corrections with the help of epitalon, a synthetic analogue of the pharmacopoeia drug epithalamin. In old (20-27 years) animals, the basal plasma levels of glucose and insulin were found to be higher, while the night melatonin level was lower in comparison with (6-8 years) young animals. After the glucose administration to old monkeys, a larger area under the curve of the plasma glucose response, a reduced glucose 'disappearance' rate, and a reduced insulin peak (5 min after the glucose administration) were observed in comparison with young animals in similar experiments. The epitalon administration to old monkeys caused the decrease in the basal levels of glucose and insulin and the increase in the basal night melatonin level. Additionally, in the case of old monkeys, epitalon decreased the area under the plasma glucose response curve, markedly increased the glucose 'disappearance' rate and normalized the plasma insulin dynamics in response to glucose administration. Yet, it has not affected the hormonal and metabolic changes in young animals. Thus, epitalon is a promising factor for restoring the age-related endocrine dysfunctions of primates.

Diurnal expression of clock genes in pineal gland and brain and plasma levels of melatonin and cortisol in Atlantic salmon parr and smolts.

PubMed

Huang, Tien-sheng; Ruoff, Peter; Fjelldal, Per G

2010-10-01

In Atlantic salmon, the preadaptation to a marine life, i.e., parr-smolt transformation, and melatonin production in the pineal gland are regulated by the photoperiod. However, the clock genes have never been studied in the pineal gland of this species. The aim of the present study was to describe the diurnal expression of clock genes (Per1-like, Cry2, and Clock) in the pineal gland and brain of Atlantic salmon parr and smolts in freshwater, as well as plasma levels of melatonin and cortisol. By employing an out-of-season smolt production model, the parr-smolt transformation was induced by subjecting triplicate groups of parr to 6 wks (wks 0 to 6) under a 12 h:12 h light-dark (LD) regime followed by 6 wks (wks 6 to 12) of continuous light (LL). The measured clock genes in both pineal gland and brain and the plasma levels of melatonin and cortisol showed significant daily variations in parr under LD in wk 6, whereas these rhythms were abolished in smolts under LL in wk 12. In parr, the pineal Per1-like and Cry2 expression peaked in the dark phase, whereas the pineal Clock expression was elevated during the light phase. Although this study presents novel findings on the clock gene system in the teleost pineal gland, the role of this system in the regulation of smoltification needs to be studied in more detail.

Cytologic features of the normal pineal gland of adults.

PubMed

Jiménez-Heffernan, José A; Bárcena, Carmen; Agra, Carolina; Asunción, Alfonso

2015-08-01

It is well known that the histology of normal pineal gland may resemble not only pineal tumors but also gliomas, owing to its cellularity which is much greater than that of normal white or gray matter. Our recent experience with a case in which part of a normal gland was submitted for intraoperative consultation, together with the scarcity of cytologic descriptions, led us to perform a cyto-histologic correlation study. In addition to the intraoperative case, we collected five pineal glands from consecutive adult autopsies. During the squash procedure, we often noted the presence of calcified grains. Smears were hypercellular, distributed in tissue fibrillary fragments and as numerous single cells, with crystalline structures. Pineal gland cells (pineocytes) were large, round, epithelioid with ill-defined cytoplasms and moderate nuclear pleomorphism. Spindle cells with greater fibrillary quality were less common. One of the most remarkable findings seen in all cases was the presence of cytoplasmic pigment. Histological evaluation and immunohistochemical staining confirmed that the tissue was normal pineal gland. The histology showed a characteristic lobular aspect and frequent corpora arenacea. The pigment seen cytologically was also encountered in histology and corresponded to lipofuscin. Cytologic features of the pineal gland are peculiar when compared to other normal structures of the central nervous system. These features correlate closely with what is seen on histology. In an adequate clinical context, and in combination with frozen sections, cytology allows a specific recognition of the pineal gland during intraoperative pathologic consultations. © 2015 Wiley Periodicals, Inc.

Melatonin Synthesis: Acetylserotonin O-Methyltransferase (ASMT) Is Strongly Expressed in a Subpopulation of Pinealocytes in the Male Rat Pineal Gland.

PubMed

Rath, Martin F; Coon, Steven L; Amaral, Fernanda G; Weller, Joan L; Møller, Morten; Klein, David C

2016-05-01

The rat pineal gland has been extensively used in studies of melatonin synthesis. However, the cellular localization of melatonin synthesis in this species has not been investigated. Here we focus on the localization of melatonin synthesis using immunohistochemical methods to detect the last enzyme in melatonin synthesis, acetylserotonin O-methyltransferase (ASMT), and in situ hybridization techniques to study transcripts encoding ASMT and two other enzymes in melatonin synthesis, tryptophan hydroxylase (TPH)-1 and aralkylamine N-acetyltransferase. In sections of the rat pineal gland, marked cell-to-cell differences were found in ASMT immunostaining intensity and in the abundance of Tph1, Aanat, and Asmt transcripts. ASMT immunoreactivity was localized to the cytoplasm in pinealocytes in the parenchyma of the superficial pineal gland, and immunopositive pinealocytes were also detected in the pineal stalk and in the deep pineal gland. ASMT was found to inconsistently colocalize with S-antigen, a widely used pinealocyte marker; this colocalization was seen in cells throughout the pineal complex and also in displaced pinealocyte-like cells of the medial habenular nucleus. Inconsistent colocalization between ASMT and TPH protein was also detected in the pineal gland. ASMT protein was not detected in extraepithalamic parts of the central nervous system or in peripheral tissues. The findings in this report are of special interest because they provide reason to suspect that melatonin synthesis varies significantly among individual pinealocytes.

Pineal-specific expression of green fluorescent protein under the control of the serotonin-N-acetyltransferase gene regulatory regions in transgenic zebrafish.

PubMed

Gothilf, Yoav; Toyama, Reiko; Coon, Steven L; Du, Shao-Jun; Dawid, Igor B; Klein, David C

2002-11-01

Zebrafish serotonin-N-acetyltransferase-2 (zfAANAT-2) mRNA is exclusively expressed in the pineal gland (epiphysis) at the embryonic stage. Here, we have initiated an effort to study the mechanisms underlying tissue-specific expression of this gene. DNA constructs were prepared in which green fluorescent protein (GFP) is driven by regulatory regions of the zfAANAT-2 gene. In vivo transient expression analysis in zebrafish embryos indicated that in addition to the 5'-flanking region, a regulatory sequence in the 3'-flanking region is required for pineal-specific expression. This finding led to an effort to produce transgenic lines expressing GFP under the control of the 5' and 3' regulatory regions of the zfAANAT-2 gene. Embryos transiently expressing GFP were raised to maturity and tested for germ cell transmission of the transgene. Three transgenic lines were produced in which GFP fluorescence in the pineal was detected starting 1 to 2 days after fertilization. One line was crossed with mindbomb and floating head mutants that cause abnormal development of the pineal and an elevation or reduction of zfAANAT-2 mRNA levels, respectively. Homozygous mutant transgenic embryos exhibited similar effects on GFP expression in the pineal gland. These observations indicate that the transgenic lines described here will be useful in studying the development of the pineal gland and the mechanisms that determine pineal-specific gene expression in the zebrafish. Published 2002 Wiley-Liss, Inc.

Melatonin Synthesis: Acetylserotonin O-Methyltransferase (ASMT) Is Strongly Expressed in a Subpopulation of Pinealocytes in the Male Rat Pineal Gland

PubMed Central

Coon, Steven L.; Amaral, Fernanda G.; Weller, Joan L.; Møller, Morten; Klein, David C.

2016-01-01

The rat pineal gland has been extensively used in studies of melatonin synthesis. However, the cellular localization of melatonin synthesis in this species has not been investigated. Here we focus on the localization of melatonin synthesis using immunohistochemical methods to detect the last enzyme in melatonin synthesis, acetylserotonin O-methyltransferase (ASMT), and in situ hybridization techniques to study transcripts encoding ASMT and two other enzymes in melatonin synthesis, tryptophan hydroxylase (TPH)-1 and aralkylamine N-acetyltransferase. In sections of the rat pineal gland, marked cell-to-cell differences were found in ASMT immunostaining intensity and in the abundance of Tph1, Aanat, and Asmt transcripts. ASMT immunoreactivity was localized to the cytoplasm in pinealocytes in the parenchyma of the superficial pineal gland, and immunopositive pinealocytes were also detected in the pineal stalk and in the deep pineal gland. ASMT was found to inconsistently colocalize with S-antigen, a widely used pinealocyte marker; this colocalization was seen in cells throughout the pineal complex and also in displaced pinealocyte-like cells of the medial habenular nucleus. Inconsistent colocalization between ASMT and TPH protein was also detected in the pineal gland. ASMT protein was not detected in extraepithalamic parts of the central nervous system or in peripheral tissues. The findings in this report are of special interest because they provide reason to suspect that melatonin synthesis varies significantly among individual pinealocytes. PMID:26950199

Hormones and immune function: implications of aging.

PubMed

Arlt, Wiebke; Hewison, Martin

2004-08-01

Aging is associated with a decline in immunity described as immunosenescence. This is paralleled by a decline in the production of several hormones, as typically illustrated by the menopausal loss of ovarian oestrogen production. However, other hormonal changes that occur with aging and that potentially impact on immune function include the release of the pineal gland hormone melatonin and pituitary growth hormone, adrenal production of dehydroepiandrosterone and tissue-specific availability of active vitamin D. It remains to be established whether hormonal changes with aging actually contribute to immunosenescence and this area is at the interface of fact and fiction, clearly inviting systematic research efforts. As a step in this direction, the present review summarizes established facts on the physiology of secretion and function of hormones that, in most cases, decline with aging and that are likely to affect the immune system.

18F-FDG PET/CT Finding of Drop Metastases from Germ Cell Tumor of Pineal Gland.

PubMed

Jain, Tarun K; Basher, Rajender K; Sood, Ashwani; Mittal, Bhagwant R; Prakash, Gaurav; Bhatia, Anmol

2017-06-01

Tumors of the pineal region are rare, accounting for fewer than 1% of all intracranial neoplasms. Fifty percent of pineal region tumors are germ cell tumors (GCTs). However, spinal seeding and extracranial metastases from intracranial GCTs are uncommon. We present a case of pineal gland GCT in which 18 F-FDG PET/CT imaging demonstrated drop metastases to the spinal cord in addition to tracer uptake in the primary lesion. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Vitamin A is a necessary factor for sympathetic-independent rhythmic activation of mitogen-activated protein kinase in the rat pineal gland.

PubMed

Guillaumond, F; Giraudet, F; Becquet, D; Sage, D; Laforge-Anglade, G; Bosler, O; François-Bellan, A M

2005-02-01

The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day physiology and behavior by sending timing messages to multiple peripheral oscillators. In the pineal gland, a major SCN target, circadian events are believed to be driven exclusively by the rhythmic release of norepinephrine from superior cervical ganglia (SCG) neurons relaying clock messages through a polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal MAPK activation that is not dependent on the SCG and whose maintenance requires vitamin A as a blood-borne factor. This finding challenges the dogma that SCG-released norepinephrine is an exclusive mediator of SCN-pineal communication and allows the assumption that humoral mechanisms are involved in pineal integration of temporal messages.

Peptidegic stimulation of differentiation of pineal immune cells.

PubMed

Linkova, N S; Khavinson, V Kh; Chalisova, N I; Katanugina, A S; Koncevaya, E A

2011-11-01

We studied cell composition of the pineal lymphoid tissue and the effect of peptides on its differentiation and proliferation capacity. It was shown that the lymphoid component of the pineal gland in organotypic culture is primarily presented by low-differentiated CD5(+)-lymphocytes, while mature T and B cells are less abundant. Dipeptide vilon stimulates differentiation of precursors into T-helpers, cytotoxic T lymphocytes, and B cells, while tetrapeptide epithalon stimulated their differentiation towards B cells. Tripeptide vesugen had no effect on differentiation capacity of immune cells of the pineal gland, but enhanced their proliferation potential. Thus, dipeptide vilon acts as an inductor of differentiation of pineal immune cells, which can play an important compensatory role in age-related atrophy of the thymus, the central organ of the immune system.

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.

PubMed

Ben-Moshe Livne, Zohar; Alon, Shahar; Vallone, Daniela; Bayleyen, Yared; Tovin, Adi; Shainer, Inbal; Nisembaum, Laura G; Aviram, Idit; Smadja-Storz, Sima; Fuentes, Michael; Falcón, Jack; Eisenberg, Eli; Klein, David C; Burgess, Harold A; Foulkes, Nicholas S; Gothilf, Yoav

2016-11-01

The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior.

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior

PubMed Central

Alon, Shahar; Vallone, Daniela; Tovin, Adi; Shainer, Inbal; Nisembaum, Laura G.; Aviram, Idit; Smadja-Storz, Sima; Fuentes, Michael; Falcón, Jack; Eisenberg, Eli; Klein, David C.; Burgess, Harold A.; Foulkes, Nicholas S.; Gothilf, Yoav

2016-01-01

The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior. PMID:27870848

Changes in plasma melatonin levels and pineal organ melatonin synthesis following acclimation of rainbow trout (Oncorhynchus mykiss) to different water salinities.

PubMed

López-Patiño, Marcos A; Rodríguez-Illamola, Arnau; Gesto, Manuel; Soengas, José L; Míguez, Jesús M

2011-03-15

Melatonin has been suggested to play a role in fish osmoregulation, and in salmonids has been related to the timing of adaptive mechanisms during smolting. It has been described that acclimation to different environmental salinities alters levels of circulating melatonin in a number of fish species, including rainbow trout. However, nothing is known regarding salinity effects on melatonin synthesis in the pineal organ, which is the main source of rhythmically produced and secreted melatonin in blood. In the present study we have evaluated, in rainbow trout, the effects of acclimation to different salinities on day and night plasma melatonin values and pineal organ melatonin synthesis. Groups of freshwater (FW)-adapted rainbow trout were placed in tanks with four different levels of water salinity (FW, 6, 12, 18 p.p.t.; parts per thousand) and maintained for 6 h or 5 days. Melatonin content in plasma and pineal organs, as well as the pineal content of serotonin (5-HT) and its main oxidative metabolite (5-hydroxyindole-3-acetic acid; 5-HIAA) were measured by high performance liquid chromatography. In addition, day-night changes in pineal organ arylalkylamine N-acetyltransferase (AANAT2) activity and aanat2 gene expression were studied. Plasma osmolalities were found to be higher in rainbow trout exposed to all salinity levels compared with the control FW groups. A salinity-dependent increase in melatonin content was found in both plasma and pineal organs. This effect was observed during the night, and was related to an increase in aanat2 mRNA abundance and AANAT2 enzyme activity, both of which also occurred during the day. Also, the levels of indoles (5-HT, 5-HIAA) in the pineal organ were negatively affected by increasing water salinity, which seems to be related to the higher recruitment of 5-HT as a substrate for the increased melatonin synthesis. A stimulatory effect of salinity on pineal aanat2 mRNA expression was also identified. These results indicate that increased external salinity promotes melatonin synthesis in the pineal organ of rainbow trout by enhancing synthesis of AANAT protein independently of its regulation by light. The possibility that pineal melatonin is a target for hormones involved in the response of fish to osmotic challenge is discussed, as well as the potential role of melatonin in the timing of osmoregulatory processes.

The dielectric properties of human pineal gland tissue and RF absorption due to wireless communication devices in the frequency range 400-1850 MHz.

PubMed

Schmid, Gernot; Uberbacher, Richard; Samaras, Theodoros; Tschabitscher, Manfred; Mazal, Peter R

2007-09-07

In order to enable a detailed analysis of radio frequency (RF) absorption in the human pineal gland, the dielectric properties of a sample of 20 freshly removed pineal glands were measured less than 20 h after death. Furthermore, a corresponding high resolution numerical model of the brain region surrounding the pineal gland was developed, based on a real human tissue sample. After inserting this model into a commercially available numerical head model, FDTD-based computations for exposure scenarios with generic models of handheld devices operated close to the head in the frequency range 400-1850 MHz were carried out. For typical output power values of real handheld mobile communication devices, the obtained results showed only very small amounts of absorbed RF power in the pineal gland when compared to SAR limits according to international safety standards. The highest absorption was found for the 400 MHz irradiation. In this case the RF power absorbed inside the pineal gland (organ mass 96 mg) was as low as 11 microW, when considering a device of 500 mW output power operated close to the ear. For typical mobile phone frequencies (900 MHz and 1850 MHz) and output power values (250 mW and 125 mW) the corresponding values of absorbed RF power in the pineal gland were found to be lower by a factor of 4.2 and 36, respectively. These results indicate that temperature-related biologically relevant effects on the pineal gland induced by the RF emissions of typical handheld mobile communication devices are unlikely.

68Ga-DOTATATE uptake in pineal gland, a rare physiological variant: case series.

PubMed

Riaz, Saima; Syed, Rizwan; Skoura, Evangelia; Alshammari, Alshaima; Gaze, Mark; Sajjan, Rakesh; Halsey, Richard; Bomanji, Jamshed

2015-11-01

(68)Ga-DOTATATE PET-CT is widely used for the evaluation of neuroendocrine tumours. Knowledge of the physiological distribution of the radiotracer is of critical importance in characterizing focal areas of uptake. In this case series, we report three paediatric cases (average age 4.7 years ± 0.6 SD) with diagnosed advanced stage IV Neuroblastoma. Two had (68)Ga-DOTATATE PET-CT scans and one underwent (68)Ga-DOTATATE PET-MRI scan to assess for suitability of molecular therapy. Focal increased tracer uptake in the pineal gland was noted in all cases with no morphological abnormality on the corresponding CT and MRI scans. The uptake within the gland was thought to be a physiological variant rather than metastases owing to the heterogeneity of somatostatin receptors expression. The pineal gland has been reported to express somatostatin receptors. The physiological distribution of (68)Ga-DOTATATE uptake in the pineal gland is not routinely seen. Furthermore, the possibility of pineal meningioma is very unlikely as pineal meningiomas are very rare and there was no convincing morphological evidence of meningiomas on CT/MRI scan.

Pineal Calcification Among Black Patients

PubMed Central

Fan, Kuang-Jaw

1983-01-01

A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification. PMID:6631985

Midline and off-midline infratentorial supracerebellar approaches to the pineal gland.

PubMed

Matsuo, Satoshi; Baydin, Serhat; Güngör, Abuzer; Miki, Koichi; Komune, Noritaka; Kurogi, Ryota; Iihara, Koji; Rhoton, Albert L

2017-06-01

OBJECTIVE A common approach to lesions of the pineal region is along the midline below the torcula. However, reports of how shifting the approach off midline affects the surgical exposure and relationships between the tributaries of the vein of Galen are limited. The purpose of this study is to examine the microsurgical and endoscopic anatomy of the pineal region as seen through the supracerebellar infratentorial approaches, including midline, paramedian, lateral, and far-lateral routes. METHODS The quadrigeminal cisterns of 8 formalin-fixed adult cadaveric heads were dissected and examined with the aid of a surgical microscope and straight endoscope. Twenty CT angiograms were examined to measure the depth of the pineal gland, slope of the tentorial surface of the cerebellum, and angle of approach to the pineal gland in each approach. RESULTS The midline supracerebellar route is the shortest and provides direct exposure of the pineal gland, although the culmen and inferior and superior vermian tributaries of the vein of Galen frequently block this exposure. The off-midline routes provide a surgical exposure that, although slightly deeper, may reduce the need for venous sacrifice at both the level of the veins from the superior cerebellar surface entering the tentorial sinuses and at the level of the tributaries of the vein of Galen in the quadrigeminal cistern, and require less cerebellar retraction. Shifting from midline to off-midline exposure also provides a better view of the cerebellomesencephalic fissure, collicular plate, and trochlear nerve than the midline approaches. Endoscopic assistance may aid exposure of the pineal gland while preserving the bridging veins. CONCLUSIONS Understanding the characteristics of different infratentorial routes to the pineal gland will aid in gaining a better view of the pineal gland and cerebellomesencephalic fissure and may reduce the need for venous sacrifice at the level of the tentorial sinuses draining the upper cerebellar surface and the tributaries of the vein of Galen.

Circadian-Related Heteromerization of Adrenergic and Dopamine D4 Receptors Modulates Melatonin Synthesis and Release in the Pineal Gland

PubMed Central

González, Sergio; Moreno-Delgado, David; Moreno, Estefanía; Pérez-Capote, Kamil; Franco, Rafael; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ortiz, Jordi

2012-01-01

The role of the pineal gland is to translate the rhythmic cycles of night and day encoded by the retina into hormonal signals that are transmitted to the rest of the neuronal system in the form of serotonin and melatonin synthesis and release. Here we describe that the production of both melatonin and serotonin by the pineal gland is regulated by a circadian-related heteromerization of adrenergic and dopamine D4 receptors. Through α1 B-D4 and β1-D4 receptor heteromers dopamine inhibits adrenergic receptor signaling and blocks the synthesis of melatonin induced by adrenergic receptor ligands. This inhibition was not observed at hours of the day when D4 was not expressed. These data provide a new perspective on dopamine function and constitute the first example of a circadian-controlled receptor heteromer. The unanticipated heteromerization between adrenergic and dopamine D4 receptors provides a feedback mechanism for the neuronal hormone system in the form of dopamine to control circadian inputs. PMID:22723743

FMRFamide-like immunoreactive neurons of the nervus terminalis of teleosts innervate both retina and pineal organ.

PubMed

Ekström, P; Honkanen, T; Ebbesson, S O

1988-09-13

The tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) was first isolated from molluscan ganglia. Subsequently, it has become clear that vertebrate brains also contain endogenous FMRFamide-like substances. In teleosts, the neurons of the nervus terminalis contain an FMRFamide-like substance, and provide a direct innervation to the retina (Proc. Natl. Acad. Sci. U.S.A., 81 [1984] 940-944). Here we report the presence of FMRFamide-immunoreactive axonal bundles in the pineal organ of Coho salmon and three-spined sticklebacks. The largest numbers of axons were observed proximal to the brain, in the pineal stalk, while the distal part of the pineal organ contained only few axons. No FMRFamide-like-immunoreactive (IR) cell bodies were observed in the pineal organ. In adult fish it was not possible to determine the origin of these axons, due to the large numbers of FMRFamide-like IR axons in the teleost brain. However, by following the development of FMRFamide-like IR neurons in the embryonic and larval stickleback brain, it was possible to conclude that, at least in newly hatched fish, FMRFamide-like IR axons that originate in the nucleus nervus terminalis reach the pineal organ. Thus, it seems there is a direct connection between a specialized part of the chemosensory system and both the retina and the pineal organ in teleost fish.

Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

PubMed

Maronde, Erik; Saade, Anastasia; Ackermann, Katrin; Goubran-Botros, Hany; Pagan, Cecile; Bux, Roman; Bourgeron, Thomas; Dehghani, Faramarz; Stehle, Jörg H

2011-08-01

Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N-acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post-transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time-of-death groups (night/dawn/day/dusk) and analyzed for daytime-dependent changes in phosphorylated AANAT (p31T-AANAT) and in acetyl-serotonin-methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T-AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T-AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T-AANAT and ASMT were often found to colocalize in cellular rod-like structures that were also partly immunoreactive for the pinealocyte process-specific marker S-antigen (arrestin) in both, human and sheep pinealocytes. Protein-protein interaction studies with p31T-AANAT, ASMT, and S-antigen demonstrated a direct association and formation of robust complexes, involving also 14-3-3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T-AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species. © 2011 John Wiley & Sons A/S.

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part II, the cystic gland.

PubMed

Sirin, Selma; de Jong, Marcus C; Galluzzi, Paolo; Maeder, Philippe; Brisse, Hervé J; Castelijns, Jonas A; de Graaf, Pim; Goericke, Sophia L

2016-07-01

Pineal cysts are a common incidental finding on brain MRI with resulting difficulties in differentiation between normal glands and pineal pathologies. The aim of this study was to assess the size and morphology of the cystic pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. In this retrospective multicenter study, 257 MR examinations (232 children, 0-5 years) were evaluated regarding pineal gland size (width, height, planimetric area, maximal cyst(s) size) and morphology. We performed linear regression analysis with 99 % prediction intervals of gland size versus age for the size parameters. Results were compared with a recent meta-analysis of pineoblastoma by de Jong et al. Follow-up was available in 25 children showing stable cystic findings in 48 %, cyst size increase in 36 %, and decrease in 16 %. Linear regression analysis gave 99 % upper prediction bounds of 10.8 mm, 10.9 mm, 7.7 mm and 66.9 mm(2), respectively, for cyst size, width, height, and area. The slopes (size increase per month) of each parameter were 0.030, 0.046, 0.021, and 0.25, respectively. Most of the pineoblastomas showed a size larger than the 99 % upper prediction margin, but with considerable overlap between the groups. We presented age-adapted normal values for size and morphology of the cystic pineal gland in children aged 0 to 5 years. Analysis of size is helpful in discriminating normal glands from cystic pineal pathologies such as pineoblastoma. We also presented guidelines for the approach of a solid or cystic pineal gland in hereditary retinoblastoma patients.

Histology-Stratified Tumor Control and Patient Survival After Stereotactic Radiosurgery for Pineal Region Tumors: A Report From the International Gamma Knife Research Foundation.

PubMed

Iorio-Morin, Christian; Kano, Hideyuki; Huang, Marshall; Lunsford, L Dade; Simonová, Gabriela; Liscak, Roman; Cohen-Inbar, Or; Sheehan, Jason; Lee, Cheng-Chia; Wu, Hsiu-Mei; Mathieu, David

2017-11-01

Pineal region tumors represent a rare and histologically diverse group of lesions. Few studies are available to guide management and the outcomes after stereotactic radiosurgery (SRS). Patients who underwent SRS for a pineal region tumor and for whom at least 6 months of imaging follow-up was available were retrospectively assessed in 5 centers. Data were collected from the medical record and histology level analyses were performed, including actuarial tumor control and survival analyses. A total of 70 patients were treated between 1989 and 2014 with a median follow-up of 47 months. Diagnoses were pineocytoma (37%), pineoblastoma (19%), pineal parenchymal tumor of intermediate differentiation (10%), papillary tumor of the pineal region (9%), germinoma (7%), teratoma (3%), embryonal carcinoma (1%), and unknown (14%). Median prescription dose was 15 Gy at the 50% isodose line. Actuarial local control and survival rates were 81% and 76% at 20 years for pineocytoma, 50% and 56% at 5 years for pineal parenchymal tumor of intermediate differentiation, 27% and 48% at 5 years for pineoblastoma, 33% and 100% at 5 years for papillary tumor of the pineal region, 80% and 80% at 20 years for germinoma, and 61% and 67% at 5 years for tumors of unknown histology. New focal neurological deficit, Parinaud syndrome, and hydrocephalus occurred in 9%, 7%, and 3% of cases, respectively. SRS is a safe modality for the management of pineal region tumors. Its specific role is highly dependent on tumor histology. As such, all efforts should be made to obtain a reliable histologic diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between pineal cyst size and aqueductal CSF flow measured by phase contrast MRI.

PubMed

Bezuidenhout, Abraham F; Kasper, Ekkehard M; Baledent, Olivier; Rojas, Rafael; Bhadelia, Rafeeque A

2018-02-23

Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI. Eleven adult patients with pineal cysts (> 1-cm in size) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. PC-MRI in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test. Patients were 39 ± 13 years (mean ± SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; p=0.009). Volume of small cysts (4954±2157 mm3) was significantly different compared to large cysts (13752±3738 mm3; p= 0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 μL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 μL/cardiac cycle (p=0.008). Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.

In vitro effects of 5-hydroxytryptophan, indoleamines and leptin on arylalkylamine N-acetyltransferase (AA-NAT) activity in pineal organ of the fish, Clarias gariepinus (Burchell, 1822) during different phases of the breeding cycle.

PubMed

Gupta, B B P; Yanthan, L; Singh, Ksh Manisana

2010-08-01

Arylalkylamine N-acetyltransferase (AA-NAT) is the rate-limiting enzyme of melatonin biosynthetic pathway. In vitro effects of 5-hydroxytryptophan (5-HTP) and indoleamines (serotonin, N-acetylserotonin and melatonin) were studied on AA-NAT activity in the pineal organ of the fish, C. gariepinus during different phases of its annual breeding cycle. Further, in vitro effects of leptin on AA-NAT activity in the pineal organ were studied in fed and fasted fishes during summer and winter seasons. Treatments with 5-HTP and indoleamines invariably stimulated pineal AA-NAT activity in a dose-dependent manner during all the phases. However, leptin increased AA-NAT activity in a dose-dependent manner only in the pineal organ of the fed fishes, but not of the fasted fishes irrespective of the seasons.

Descartes' pineal neuropsychology.

PubMed

Smith, C U

1998-02-01

The year 1996 marked the quattrocentenary of Descartes' birth. This paper reviews his pineal neuropsychology. It demonstrates that Descartes understood the true anatomical position of the pineal. His intraventricular pineal (or glande H) was a theoretical construct which allowed him to describe the operations of his man-like "earthen machine." In the Treatise of Man he shows how all the behaviors of such machines could then be accounted for without the presence of self-consciousness. Infrahuman animals are "conscious automata." In Passions of the Soul he adds, but only for humans, self-consciousness to the machine. In a modern formulation, only humans not only know but know that they know. Copyright 1998 Academic Press.

Mixed pineal mature teratoma and germinoma in two brothers of the fraternal triplets.

PubMed

Grahovac, Gordan; Alden, Tord; Nitin, Wadhwani

2017-05-01

Intracranial teratomas are rare germ cell neoplasms that contain tissues derived from all three germ cell layers and most commonly occurring during childhood. This is the first report of pineal region mixed mature teratoma and germinoma in two fraternal brothers of fraternal triplets. We report the case of a mixed mature teratoma and germinoma of the pineal region in two brothers of fraternal triplets. Older brother was initially diagnosed at the age of 11 years with the pure teratoma of the pineal region but the review of the pathology 3 years after initial surgery revealed the mixed mature teratoma with 5% germinomatous component. The younger brother was diagnosed at the age of 13 years with the mixed mature teratoma with 10% germinomatous component tumor of the pineal region. Younger brother has been treated with adjuvant chemo-radiotherapy and older brother was treated without adjuvant therapy. Both brothers had no recurrence. Pineal mature teratomas have a good prognosis, in contrast to their immature or mixed counterparts. A rigorous histological examination of the tumor samples is mandatory, in order to not omit a mixed contingent within the tumor.

Contrasting effects of vortioxetine and paroxetine on pineal gland biochemistry in a tryptophan-depletion model of depression in female rats.

PubMed

Franklin, M; Hlavacova, N; Li, Y; Bermudez, I; Csanova, A; Sanchez, C; Jezova, D

2017-10-03

We studied the effects of the multi-modal antidepressant, vortioxetine and the SSRI, paroxetine on pineal melatonin and monoamine synthesis in a sub-chronic tryptophan (TRP) depletion model of depression based on a low TRP diet. Female Sprague-Dawley rats were randomised to groups a) control, b) low TRP diet, c) low TRP diet+paroxetine and d) low TRP diet+vortioxetine. Vortioxetine was administered via the diet (0.76mg/kg of food weight) and paroxetine via drinking water (10mg/kg/day) for 14days. Both drugs resulted in SERT occupancies >90%. Vortioxetine significantly reversed TRP depletion-induced reductions of pineal melatonin and serotonin (5-HT) and significantly increased pineal noradrenaline NA. Paroxetine did none of these things. Other studies suggest pineal melatonin synthesis may involve N-methyl-d-aspartate (NMDA) receptors and glutamatergic modulation. Here observed changes may be mediated via vortioxetine's strong 5-HT reuptake blocking action together with possible additional effects on glutamate neurotransmission in the pineal via NMDA receptor-modulation and possibly with added impetus from increased NA output. Copyright © 2017 Elsevier Inc. All rights reserved.

Pineal melatonin synthesis in Syrian hamsters: A summary

NASA Astrophysics Data System (ADS)

Rollag, M. D.

1982-12-01

During the past decade there has been ample documentation of the proposition that the pineal gland mediates photoperiodic influences upon reproductive behavior of hamsters. It is commonly hypothesized that the pineal gland expresses its activity by transformation of photoperiodic information into an hormonal output, that hormone being melatonin. If this hypothesis is correct, there must be some essential diffrence in melatonin's output when hamsters are exposed to different photoperiodic environments. The experiments summarized in this communication analyze pineal melatonin contents in Syrian hamsters maintained in a variety of photoperiodic conditions during different physiological states. The results demonstrate that adult hamsters have a daily surge in pineal melatonin content throughout their lifetime when exposed to simulated annual photoperiodic cycles. There is some fluctuation in the amount of pineal melatonin produced during different physiological states and photoperiodic environments, but these fluctuations seem small when compared to those normally found for other regulatory hormones. When hamsters are exposed to different photoperiodic regimens, the daily melatonin surge maintains a relatively constant phase relationship with respect to the onset of daily activity. There is a concomitant change in its phase relationship with respect to light-dark transitions.

Biochemical and hormonal evaluation of pineal glands exposed in vitro to magnetic fields. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, L.E.; Leung, F.C.; Miller, D.L.

It has been reported that exposure to extremely low frequency (ELF) magnetic fields can significantly alter pineal melatonin metabolism in vivo. However, whether such changes are due to direct or indirect effects of field exposure has not been clearly demonstrated. The objective of this research project was to examine the effects of magnetic fields on melatonin metabolism in pineal glands in vitro. Chicken pineal glands were cultured in a modified incubator encircled by a magnetic field exposure system. The incubator, that was remote from but attached to a standard laboratory incubator, contained a regulated light source for modulation of themore » light/dark cycle (12:12 L/D). Pineal glands from 4--6 week old chickens were maintained under 95% O{sub 2}, 5% CO{sub 2} in a static culture system. Because of problems due to contamination and loss of viability of such a system, a perfusion system was developed for EMF studies. Both single and multiple chicken pineal glands were used in the perfusion studies and were kept viable in the perfusion chamber by a continuous flow of medium at 39 C for up to 8 days. Perfusate samples were collected into a fraction collector and were subsequently kept frozen at {minus} 20 C until assays were performed. Melatonin secreted by the cultured pineal glands and released into the medium was measured by a melatonin double antibody radioimmunoassay (RIA) using {sup 125}I-melatonin as the label.« less

A Novel Method to Measure the Tentorial Angle and the Implications on Surgeries of the Pineal Region.

PubMed

Syed, Hasan R; Jean, Walter C

2018-03-01

There is no standard way to define the angle of the tentorium. The current trend to use the Twining line to define this angle has significant pitfalls. The goal of the current study was to provide a new and accurate way to measure the tentorial angle and demonstrate its impact on surgeries of the pineal region. A new technique (n-angle) to measure the tentorial angle was introduced using the floor of the fourth ventricle and the torcula. Comparisons with older techniques were made to illustrate reliability. Midline sagittal MR images were used to measure the tentorial angle in 240 individuals to obtain population-based data. A cohort of 8 patients who underwent either the infratentorial or the transtentorial approach to the pineal or upper vermian region were examined in search of correlations between tentorial angle and surgical approach. The data in this study showed that the Twining line technique understates the tentorial angle in people with low-lying torcula. The n-angle is more reliable in reflecting the true steepness of the tentorium regardless of torcula position. On average, men have slightly steeper tentoriums. In the clinical cohort, all patients who underwent infratentorial surgery had tentorial angles <55°, whereas the majority of patients who underwent transtentorial surgeries had angles >67°. The n-angle provides a reliable and accurate way to describe the slope of the tentorium. The population-based average of 60° may be a useful measurement to influence the choice of surgical approach, either under or through the tentorium, to the pineal region. Copyright © 2017 Elsevier Inc. All rights reserved.

Control of pineal indole biosynthesis by changes in sympathetic tone caused by factors other than environmental lighting.

NASA Technical Reports Server (NTRS)

Lynch, H. J.; Eng, J. P.; Wurtman, R. J.

1973-01-01

Description of experimental investigations showing that, in addition to environmental lighting, other manipulations known to modify sympathetic tone can also modify pineal indole biosynthesis. Comparable alterations in sympathetic tone that occur in response to activity or feeding cycles may be instrumental in generating the pineal rhythms that persist in the absence of light-dark cycle.

[Morphological structure of rat epiphysis exposed to electromagnetic radiation from communication devices].

PubMed

Yashchenko, S G; Rybalko, S Yu

Pineal gland is one of the most important components of homeostasis - the supporting system of the body. It participates in the launch of stress responses, restriction of their development, prevention of adverse effects on the body. There was proved an impact of electromagnetic radiation on the epiphysis. However, morphological changes in the epiphysis under exposure to electromagnetic radiation of modern communication devices are studied not sufficiently. For the time present the population is daily exposed to electromagnetic radiation, including local irradiation on the brain. These date determined the task of this research - the study of the structure of rat pineal gland under the exposure to electromagnetic radiation from personal computers and mobile phones. These date determined the task of this research - the study of the structure of rat pineal gland under the exposure to electromagnetic radiation from personal computers and mobile phones. Performed transmission electron microscopy revealed signs of degeneration of dark and light pinealocytes. These signs were manifested in the development of a complex of general and specific morphological changes. There was revealed the appearance of signs of aging and depletion transmission electron microscopy both in light and dark pinealocytes. These signs were manifested in the accumulation of lipofuscin granules and electron-dense "brain sand", the disappearance of nucleoli, cytoplasm vacuolization and mitochondrial cristae enlightenment.

Neuroendocrine mediated effects of electromagnetic-field exposure: Possible role of the pineal gland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, W.B.; Stevens, R.G.; Anderson, L.E.

Reports from recent epidemiological studies have suggested a possible association between extremely low frequently (ELF; including 50- or 60-Hz) electric- and magnetic-field exposure, and increased risk of certain cancers, depression, and miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological factor in these effects. Work in our laboratory and elsewhere has shown that ELF electromagnetic-field exposure can alter the normal circadian rhythm of melatonin synthesis and release in the pineal gland. Consequences of reduced or inappropriately timed melatonin release on the endocrine, neuronal, and immune systems are discussed. Laboratory data linking ELF field exposure to changes in pineal circadianmore » rhythms in both animal and humans are reviewed. The authors suggest that the pineal gland, in addition to being a convenient locus for measuring dyschronogenic effects of ELF field exposure, may play a central role in biological response to these fields via alterations in the melatonin signal.« less

Characterization of the Expression of Basigin Gene Products Within the Pineal Gland of Mice.

PubMed

Tokar, Derek; van Ekeris, Leslie; Linser, Paul J; Ochrietor, Judith D

2017-08-01

The expression of Basigin gene products and monocarboxylate transporter-1 (MCT1) has been investigated within the mammalian neural retina and suggests a role for these proteins in cellular metabolism within that tissue. The purpose of the present study was to investigate the expression of these same proteins in the pineal gland of the mouse brain. Mouse pineal gland and neural retina RNA and protein were subjected to quantitative reverse transcription-polymerase chain reaction and immunoblotting analyses. In addition, paraffin-embedded sections of each tissue were analyzed for expression of Basigin gene products and MCT1 via immunohistochemistry. The results indicate that MCT1 and Basigin variant-2, but not Basigin variant-1, are expressed within the mouse pineal gland. The expression of Basigin variant-2 and MCT1 was localized to the capsule surrounding the gland. The position and relative amounts of the gene products suggest that they play a much less prominent role within the pineal gland than in the neural retina.

A comparative study of annual changes in the pineal gland morphology with reference to the influence of melatonin on testicular activity in tropical birds, Psittacula cyanocephala and Ploceus philippinus.

PubMed

Chakraborty, S

1993-10-01

The aim of the present comparative investigation was to examine annual pineal cytological changes and the action of melatonin in relation to testicular activity in two wild tropical avian species. The findings revealed that in both blossomheaded parakeets (Psittacula cyanocephala) and Indian weaver birds (Ploceus philippinus) the pineal gland was inactive, with reduced karyometric values during the breeding season. A pinealoactive phase showing significantly increased pinealocyte nuclear diameter corresponded with the nonbreeding phase. Administration of melatonin (250 micrograms/100 g body wt) for 10 consecutive days caused significant involution of testes during the breeding phase, although it failed to alter reproductive activity during the nonbreeding phase. The results indicated that the pineal gland activity varied inversely with the seasonal testicular weight cycle and the antigonadal influence of melatonin appeared to be phase dependent, which corroborated the inverse temporal relationship of the pineal gland and male reproductive activity examined in the two tropical avian species.

The originality of Descartes' theory about the pineal gland.

PubMed

Lokhorst, G J; Kaitaro, T T

2001-03-01

René Descartes thought that the pineal gland is the part of the body with which the soul is most immediately associated. Several prominent historians (such as Soury, Thorndike and Sherrington) have claimed that this idea was not very original. We re-examine the evidence and conclude that their assessment was wrong. We pay special attention to the thesis about the pineal gland which Jean Cousin defended in January, 1641.

The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light

PubMed Central

Ben-Moshe, Zohar; Alon, Shahar; Mracek, Philipp; Faigenbloom, Lior; Tovin, Adi; Vatine, Gad D.; Eisenberg, Eli; Foulkes, Nicholas S.; Gothilf, Yoav

2014-01-01

Light constitutes a primary signal whereby endogenous circadian clocks are synchronized (‘entrained’) with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3′UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light. PMID:24423866

The morphology of the pineal gland of the yellow-toothed cavy (Galea Spixii Wagler, 1831) and red-rumped agouti (Dasyprocta leporina linnaeus, 1758).

PubMed

Câmara, Felipe Venceslau; Lopes, Igor Renno Guimarães; de Oliveira, Gleidson Benevides; Bezerra, Ferdinando Vinicius Fernandes; de Oliveira, Radan Elvis Matias; Oliveira Júnior, Carlos Magno; Silva, Alexandre Rodrigues; de Oliveira, Moacir Franco

2015-08-01

The pineal gland is an endocrine gland found in all mammals. This article describes the morphology of this important gland in two species of Caviideae, namely the yellow-toothed cavy and the red-rumped agouti. Ten adult animals of the two species used in current analysis were retrieved from the Center for the Multiplication of Wild Animals (CEMAS/UFERSA) and euthanized. The glands were removed and photographed in situ and ex situ. They were fixed in a paraformaldehyde solution 4% or glutaraldehyde 2.5% solution and submitted to routine histological techniques respectively for light and scanning electron microscopy. Macroscopically, the pineal gland with its elongated structure may be found between the cerebral hemispheres facing the rostral colliculi. Microscopically, pinealocytes and some glia cells were predominant. Contrastingly, to the cavy's pineal gland, a capsule covered the organ in the agouti, with the emission of incomplete septa to the interior, which divided it into two lobules. Light and scanning electron microscopes failed to show calcareous concretions in the pineal gland. Based on the topography of the cavy's and agouti's pineal gland, it may be classified as supra-callosum and ABC type. © 2015 Wiley Periodicals, Inc.

Pigmented Cells in the Pineal Gland of Female Viscacha (Lagostomus maximus maximus): A Histochemical and Ultrastructural Study

PubMed Central

Busolini, Fabricio Ivan; Rodríguez, Graciela Beatriz; Filippa, Verónica Palmira

2017-01-01

The presence of pigment has been demonstrated in different nervous structures such as those of retina, substantia nigra, and locus coeruleus. These pigments have also been described in the pineal gland of different mammal species. Histochemical and ultrastructural studies of the pineal gland of female viscacha (Lagostomus maximus maximus) were performed to analyze the presence of pigmented cells under natural conditions and to evaluate a probable relation between pigment content and glandular activity during pregnancy. The following techniques were applied: hematoxylin-eosin, phosphotungstic acid-hematoxylin, Masson-Fontana silver, DOPA histochemistry, Schmorl's reaction and toluidine blue. Estradiol and progesterone serum levels were determined by RIA. The ultrastructural features of the pineal pigment granules were also analyzed. Pigment granules were observed in a random distribution, but the pigmented cells were frequently found near blood vessels. The pineal pigment was histochemically identified as melanin. Differences in the amount of pigmented cells were found between pregnant and nonpregnant viscachas. The ultrastructural analysis revealed the presence of premelanosomes and melanosomes. Estradiol and progesterone levels vary during pregnancy. In conclusion, the changes in the amount of pigment content and hormone levels may indicate that the pineal gland of female viscacha is susceptible to endocrine variations during pregnancy. PMID:29391866

Prevalence of pineal gland calcification as an incidental finding in patients referred for implant dental therapy.

PubMed

Mutalik, Sunil; Tadinada, Aditya

2017-09-01

Pineal gland calcification has been proposed to play a role in the pathogenesis of Alzheimer disease. This study evaluated the prevalence and extent of pineal gland calcification in cone-beam computed tomography (CBCT) scans of patients referred for dental implant therapy who could possibly be a vulnerable group for this condition. A retrospective evaluation of 500 CBCT scans was conducted. Scans that showed the area where the pineal gland was located were included. The scans were initially screened by a single observer to record the prevalence and extent of calcification. Six weeks following the completion of the study, another investigator randomly reviewed and selected 50 scans to investigate inter-observer variation, which was evaluated using reliability analysis statistics. The prevalence and measurements of the calcifications were reported using descriptive statistics. The chi-square test was used to compare the prevalence between males and females. The prevalence of pineal gland calcification was 58.8%. There was no statistically significant correlation between age and the extent of the calcification. The prevalence of calcification was 58.6% in females and 59.0% in males. The average anteroposterior measurement was 3.73±1.63 mm, while the average mediolateral measurement was 3.47±1.31 mm. The average total calcified area was 9.79±7.59 mm 2 . The prevalence of pineal gland calcification was high in patients undergoing implant therapy. While not all pineal gland calcifications lead to neurodegenerative disorders, they should be strongly considered in the presence of any symptoms as a reason to initiate further investigations.

Update on the management of pineal cysts: Case series and a review of the literature.

PubMed

Berhouma, M; Ni, H; Delabar, V; Tahhan, N; Memou Salem, S; Mottolese, C; Vallee, B

2015-01-01

The natural history of pineal cysts still remains unclear. Incidental pineal cysts have become more common which raises the question of their management. Symptomatic pineal cysts may require a surgical solution but therapeutic indications have not yet been clearly established. From 1986 to 2012, 26 patients with pineal cysts were identified. Their medical records were retrospectively assessed focusing on the initial symptoms, imaging characteristics of the cyst, management strategy, operative technique and their complications, as well as the latest follow-up. A systematic review of the literature is also presented. Twenty-six patients with pineal cysts were identified. The mean age was 23.5 years ranging from 7 to 49 years. Symptoms included intracranial hypertension with obstructive hydrocephalus in 18 cases and oculomotor anomalies in 12 cases. Two adult cases presented with non-specific headaches and did not require surgery. Twenty patients were operated via a suboccipital transtentorial approach with total removal of the cyst in 70% of the cases, while the remaining 4 cases were treated with an intraventricular endoscopic marsupialization associating a third ventriculostomy. Four patients required a preoperative ventriculo-peritoneal shunt due to life-threatening obstructive hydrocephalus. Overall, peri-operative mortality was nil. In the two non-operated patients, the cyst remained stable and no recurrences were observed in all operated patients with a mean follow-up of 144 months. In the majority of incidental pineal cysts, a clinical and imaging follow-up is sufficient but occasionally not required especially in adults as very rare cases of increase in size have been reported. Copyright © 2014. Published by Elsevier Masson SAS.

Endogenous 6-Hydroxymelatonin Excretion and Subsequent Risk of Breast Cancer: A Prospective Study

DTIC Science & Technology

2007-03-01

4 INTRODUCTION Melatonin (N-acetyl-5methoxtryptamine) is synthesized and released by the pineal gland ...Cohen M. Lippman M. Chabner B. Role of pineal gland in aetiology and treatment of breast cancer. Lancet. 2(8094):814-6, 1978. Coogan PF. Clapp...49, 1986. Blask DE. Pelletier DB. Hill SM. Lemus-Wilson A. Grosso DS. Wilson ST. Wise ME. Pineal melatonin inhibition of tumor promotion in the N

Acute and Delayed Effects of Melatonin: Operational Significance

DTIC Science & Technology

2000-03-01

In mammals its primary sites circadian zeitgeber in humans have been much of production are the pineal gland and the retina, discussed (e.g. 5...proposed as an methoxytryptamine (melatonin). The rhythm of endogenous sleep substance, as an opener of the pineal synthesis is generated in the...melatonin in the blind. J Biol Rhythms 1996; 12:16-25. References 1. Arendt J. Melatonin and the manmmalian pineal 14. Sack R L, Lewy AJ, Blood ML

Antioxidant properties of melatonin--an emerging mystery.

PubMed

Beyer, C E; Steketee, J D; Saphier, D

1998-11-15

Over three centuries ago, the French philosopher René Descartes described the pineal gland as "the seat of the soul." However, it was not until the late 1950s that the chemical identity and biosynthesis of melatonin, the principal hormone secreted by the pineal body, were revealed. Melatonin, named from the Greek melanos, meaning black, and tonos, meaning color, is a biogenic amine with structural similarities to serotonin. The mechanisms mediating the synthesis of melatonin are transcriptionally regulated by the photoperiodic environment. Once synthesized, the neurohormone is a biologic modulator of mood, sleep, sexual behavior, reproductive alterations, immunologic function, and circadian rhythms. Moreover, melatonin exerts its regulatory roles through high-affinity, pertussis toxin-sensitive, G-protein (or guanine nucleotide binding protein) coupled receptors that reside primarily in the eye, kidney, gastrointestinal tract, blood vessels, and brain. Additional evidence also indicates a role for melatonin in aging and age-related diseases, probably related to its efficient free radical scavenger (or antioxidant) activity. The potential clinical benefit of melatonin as an antioxidant is remarkable, suggesting that it may be of use in the treatment of many pathophysiological disease states including various cancers, hypertension, pulmonary diseases, and a variety of neurodegenerative diseases such as Alzheimer's disease. This review summarizes the biosynthesis of melatonin and its many endocrine and physiological functions, including its therapeutic potential in human disease states. Emphasis is placed on the recent speculations indicating that this pineal hormone serves as an endogenous antioxidant agent with proficient free radical scavenging activity.

Melatonin: the dark force.

PubMed

Bergstrom, W H; Hakanson, D O

1998-01-01

Although the pineal gland was described 2,300 years ago, its functions remained obscure and productive research was limited until 1958, when Lerner and associates defined melatonin. In 1965 Wurtman and Axelrod advanced the "melatonin hypothesis," according to which the pineal gland acts as a transducer responding to changes in circumambient light by changing its rates of melatonin output. Sites and mechanisms of melatonin action are still poorly understood. Two consistent effects are the induction of sleep and an antigonadotropic influence on reproductive structure and behavior. The former is demonstrable and clinically useful in human subjects; the latter has been shown in birds, rodents, and sheep. Alteration of skin color by the contraction of melanophores was effected by pineal extracts before the discovery of melatonin. This phenomenon, seen in reptiles, amphibians, and fish, has received little recent attention. Areas of greater interest and potential importance include the antimitotic effects of melatonin on some types of tumor cells in culture and the apparent in vivo protection of immunocompetent lymphocytes during chronic stress, which reduces the functional capacity of lymphocytes in control rodents. Clinical application of the antimitotic and immunosupportive properties of melatonin seems likely in the near future. Unfortunately, this innocent molecule has been touted in two recent books and many advertisements as an aphrodisiac, rejuvenator, protector against disease, and general wonder-worker. Because interest in melatonin is high, all physicians can expect questions and may have use for the information provided in this review.

The pineal gland: A model for adrenergic modulation of ubiquitin ligases.

PubMed

Vriend, Jerry; Liu, Wenjun; Reiter, Russel J

2017-01-01

A recent study of the pineal gland of the rat found that the expression of more than 3000 genes showed significant day/night variations (The Hartley dataset). The investigators of this report made available a supplemental table in which they tabulated the expression of many genes that they did not discuss, including those coding for components of the ubiquitin proteasome system. Herein we identify the genes of the ubiquitin proteasome system whose expression were significantly influenced by environmental lighting in the Hartley dataset, those that were stimulated by DBcAMP in pineal glands in culture, and those that were stimulated by norepinephrine. Using the Ubiquitin and Ubiquitin-like Conjugation Database (UUCA) we identified ubiquitin ligases and conjugases, and deubiquitinases in the Hartley dataset for the purpose of determining whether expression of genes of the ubiquitin proteasome pathway were significantly influenced by day/night variations and if these variations were regulated by autonomic innervation of the pineal gland from the superior cervical ganglia. In the Hartley experiments pineal glands groups of rats sacrificed during the day and groups sacrificed during the night were examined for gene expression. Additional groups of rats had their superior cervical ganglia removed surgically or surgically decentralized and the pineal glands likewise examined for gene expression. The genes with at least a 2-fold day/night significant difference in expression included genes for 5 ubiquitin conjugating enzymes, genes for 58 ubiquitin E3 ligases and genes for 6 deubiquitinases. A 35-fold day/night difference was noted in the expression of the gene Sik1, which codes for a protein containing both an ubiquitin binding domain (UBD) and an ubiquitin-associated (UBA) domain. Most of the significant differences in these genes were prevented by surgical removal, or disconnection, of the superior cervical ganglia, and most were responsive, in vitro, to treatment with a cyclic AMP analog, and norepinephrine. All previously described 24-hour rhythms in the pineal require an intact sympathetic input from the superior cervical ganglia. The Hartley dataset thus provides evidence that the pineal gland is a highly useful model for studying adrenergically dependent mechanisms regulating variations in ubiquitin ligases, ubiquitin conjugases, and deubiquitinases, mechanisms that may be physiologically relevant not only in the pineal gland, but in all adrenergically innervated tissue.

The pineal gland: A model for adrenergic modulation of ubiquitin ligases

PubMed Central

Liu, Wenjun; Reiter, Russel J.

2017-01-01

Introduction A recent study of the pineal gland of the rat found that the expression of more than 3000 genes showed significant day/night variations (The Hartley dataset). The investigators of this report made available a supplemental table in which they tabulated the expression of many genes that they did not discuss, including those coding for components of the ubiquitin proteasome system. Herein we identify the genes of the ubiquitin proteasome system whose expression were significantly influenced by environmental lighting in the Hartley dataset, those that were stimulated by DBcAMP in pineal glands in culture, and those that were stimulated by norepinephrine. Purpose Using the Ubiquitin and Ubiquitin-like Conjugation Database (UUCA) we identified ubiquitin ligases and conjugases, and deubiquitinases in the Hartley dataset for the purpose of determining whether expression of genes of the ubiquitin proteasome pathway were significantly influenced by day/night variations and if these variations were regulated by autonomic innervation of the pineal gland from the superior cervical ganglia. Methods In the Hartley experiments pineal glands groups of rats sacrificed during the day and groups sacrificed during the night were examined for gene expression. Additional groups of rats had their superior cervical ganglia removed surgically or surgically decentralized and the pineal glands likewise examined for gene expression. Results The genes with at least a 2-fold day/night significant difference in expression included genes for 5 ubiquitin conjugating enzymes, genes for 58 ubiquitin E3 ligases and genes for 6 deubiquitinases. A 35-fold day/night difference was noted in the expression of the gene Sik1, which codes for a protein containing both an ubiquitin binding domain (UBD) and an ubiquitin-associated (UBA) domain. Most of the significant differences in these genes were prevented by surgical removal, or disconnection, of the superior cervical ganglia, and most were responsive, in vitro, to treatment with a cyclic AMP analog, and norepinephrine. All previously described 24-hour rhythms in the pineal require an intact sympathetic input from the superior cervical ganglia. Conclusions The Hartley dataset thus provides evidence that the pineal gland is a highly useful model for studying adrenergically dependent mechanisms regulating variations in ubiquitin ligases, ubiquitin conjugases, and deubiquitinases, mechanisms that may be physiologically relevant not only in the pineal gland, but in all adrenergically innervated tissue. PMID:28212404

The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin.

PubMed

Bulc, Michał; Lewczuk, Bogdan; Prusik, Magdalena; Całka, Jarosław

2013-05-01

Innervation of the mammalian pineal gland during prenatal development is poorly recognized. Therefore, immunofluorescence studies of the pineals of 70- and 90-day-old foetuses of the domestic pig were performed using antibodies against tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON). The investigated glands were supplied by numerous nerve fibres containing TH and DβH. The density of these fibres was higher in the distal and middle parts of the gland than in the proximal one. NPY and CPON were identified in the majority of DβH-positive fibres as well as in a small population of DβH-negative fibres localized mainly in the proximal part of the pineal. The immunoreactive fibres were more numerous in 90-day-old foetuses than in 70-day-old ones. The effect of norepinephrine on melatonin secretion by the foetal pineals in the short-term organ culture was studied to determine the role of DβH-positive fibres during prenatal life. For the same purpose melatonin was measured in the blood in the umbilical cords and in the jugular vein of the mother. The pineals of both groups of foetuses did not secrete melatonin in the organ culture, independently of the presence or absence of norepinephrine in the medium. Melatonin concentrations in the blood in the umbilical cords of foetuses from the same litter and in the jugular vein of their mother were similar. The presence of adrenergic nerve fibres in the pig pineal during gestation does not seem to be associated with the control of melatonin secretion.

Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis.

PubMed

Fernandes, Pedro A; Tamura, Eduardo K; D'Argenio-Garcia, Letícia; Muxel, Sandra M; da Silveira Cruz-Machado, Sanseray; Marçola, Marina; Carvalho-Sousa, Cláudia E; Cecon, Erika; Ferreira, Zulma S; Markus, Regina P

2017-01-01

The nocturnal production of melatonin by the pineal gland is triggered by sympathetic activation of adrenoceptors and may be modulated by immunological signals. The effect of glucocorticoids on nocturnal melatonin synthesis is controversial; both stimulatory and inhibitory effects have been reported. During pathophysiological processes, an increased sympathetic tonus could result in different patterns of adrenoceptor activation in the pineal gland. Therefore, in this investigation, we evaluated whether the pattern of adrenergic stimulation of the pineal gland drives the direction of the glucocorticoid effect on melatonin production. The corticosterone effect on the pineal hormonal production induced by β-adrenoceptor or β+α1-adrenoceptor activation was evaluated in cultured glands. We also investigated whether the in vivo lipopolysaccharide (LPS)-induced inhibition of melatonin is dependent on the interaction of glucocorticoids and the α1-adrenoceptor in adrenalectomized animals and on the in vivo blockade of glucocorticoid receptors (GRs) or the α1-adrenoceptor. Corticosterone potentiated β-adrenoceptor-induced pineal melatonin synthesis, whilst corticosterone-dependent inhibition was observed when melatonin production was induced by β+α1-adrenoceptors agonists. The inhibitory effect of corticosterone is mediated by GR, as it was abolished in the presence of a GR antagonist. Moreover, LPS-induced reduction in melatonin nocturnal plasma content was reversed by adrenalectomy and by antagonizing GR or α1-adrenoceptors. The dual effect of corticosterone on pineal melatonin synthesis is determined by the activation pattern of adrenoceptors (β or β+α1) in the gland during GR activation, suggesting that increased activation of the sympathetic system and the hypothalamic-pituitary-adrenal axis are necessary for the control of melatonin production during defense responses. © 2016 S. Karger AG, Basel.

Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland.

PubMed

Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B

2015-01-01

Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.

[Expression profiles of miRNA-182 and Clock mRNA in the pineal gland of neonatal rats with hypoxic-ischemic brain damage].

PubMed

Han, Xing; Ding, Xin; Xu, Li-Xiao; Liu, Ming-Hua; Feng, Xing

2016-03-01

To study the changes of miRNA expression in the pineal gland of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible roles of miRNA in the pathogenesis of circadian rhythm disturbance after HIBD. Seven-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups: HIBD and sham-operated. HIBD was induced according to the Rice-Vannucci method. The pineal glands were obtained 24 hours after the HIBD event. The expression profiles of miRNAs were determined using GeneChip technigue and quantitative real-time PCR (RT-PCR). Then the miRNA which was highly expressed was selected. The expression levels of the chosen miRNA were detected in different tissues (lungs, intestines, stomach, kidneys, cerebral cortex, pineal gland). RT-PCR analysis was performed to measure the expression profiles of the chosen miRNA and the targeted gene Clock mRNA in the pineal gland at 0, 24, 48 and 72 hours after HIBD. miRNA-182 that met the criteria was selected by GeneChip and RT-PCR. miRNA-182 was highly expressed in the pineal gland. Compared with the sham-operated group, the expression of miRNA-182 was significantly up-regulated in the pineal gland at 24 and 48 hours after HIBD (P<0.05). Compared with the sham-operated group, Clock mRNA expression in the HIBD group increased at 0 hour after HIBD, decreased at 48 hours after HIBD and increased at 72 hours after HIBD (P<0.05). miRNA-182 may be involved in the pathogenesis of circadian rhythm disturbance after HIBD.

Transcriptional regulation of arylalkylamine-N-acetyltransferase-2 gene in the pineal gland of the gilthead seabream.

PubMed

Zilberman-Peled, B; Appelbaum, L; Vallone, D; Foulkes, N S; Anava, S; Anzulovich, A; Coon, S L; Klein, D C; Falcón, J; Ron, B; Gothilf, Y

2007-01-01

Pineal serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase; AANAT) is considered the key enzyme in the generation of circulating melatonin rhythms; the rate of melatonin production is determined by AANAT activity. In all the examined species, AANAT activity is regulated at the post-translational level and, to a variable degree, also at the transcriptional level. Here, the transcriptional regulation of pineal aanat (aanat2) of the gilthead seabream (Sparus aurata) was investigated. Real-time polymerase chain reaction quantification of aanat2 mRNA levels in the pineal gland collected throughout the 24-h cycle revealed a rhythmic expression pattern. In cultured pineal glands, the amplitude was reduced, but the daily rhythmic expression pattern was maintained under constant illumination, indicating a circadian clock-controlled regulation of seabream aanat2. DNA constructs were prepared in which green fluorescent protein was driven by the aanat2 promoters of seabream and Northern pike. In vivo transient expression analyses in zebrafish embryos indicated that these promoters contain the necessary elements to drive enhanced expression in the pineal gland. In the light-entrainable clock-containing PAC-2 zebrafish cell line, a stably transfected seabream aanat2 promoter-luciferase DNA construct exhibited a clock-controlled circadian rhythm of luciferase activity, characteristic for an E-box-driven expression. In NIH-3T3 cells, the seabream aanat2 promoter was activated by a synergistic action of BMAL/CLOCK and orthodenticle homeobox 5 (OTX5). Promoter sequence analyses revealed the presence of the photoreceptor conserved element and an extended E-box (i.e. the binding sites for BMAL/CLOCK and OTX5 that have been previously associated with pineal-specific and rhythmic gene expression). These results suggest that seabream aanat2 is a clock-controlled gene that is regulated by conserved mechanisms.

Endogenous 6-Hydroxymelatonin Excretion and Subsequent Risk of Breast Cancer: A Prospective Study

DTIC Science & Technology

2008-03-01

pineal gland in response to darkness. Thus, melatonin displays a strong variation during a 24- hour period: its serum levels are low during daylight...in the United States. Journal of the National Cancer Institute. 87(3):227-8, 1995. Cohen M. Lippman M. Chabner B. Role of pineal gland in aetiology...hormone that is produced primarily by the pineal gland , also follows a circadian rhythm of approximately 24 hours; melatonin is secreted exclusively

Pineal-Induced Depression of Free Thyroxine in Syrian Hamsters

DTIC Science & Technology

1985-01-01

activation by blind- ness in Syrian hamsters, can influence free 14 concentration. MATERIALS AND METHODS Male golden hamsters, Mesocricetus auratus...considered that the changes in T4 passively result from pineal- induced hypogonadism and the possible resultant effects on T4 serum bind- ing proteins...the presence of pineal-induced hypogonadism and that, like T4 and FT41, -• ’. 328 Vaughan and Pruitt TESrE S PROSTATE 0.6 80- 20 gn Mgm ,... =_ 9 Mg_

Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, L.E.; Hilton, D.I.; Phillips, R.D.

Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were comparedmore » in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.« less

Cysteamine effects on somatostatin, catecholamines, pineal NAT and melatonin in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, S.M.; Champney, T.H.; Steger, R.W.

The thiol reagent cysteamine was administered to adult male rats with the aim of investigating its effect on different neural and pineal components. As expected, immunoreactive somatostatin decreased in the median eminence (ME) (p less than 0.05) and gastric antrum (p less than 0.05) after cysteamine; however, no significant change was observed in the pineal IRS content after drug treatment. A decrease in norepinephrine was observed in the ME (p less than 0.001), hypothalamus (p less than 0.001) and pineal gland (p less than 0.05), together with a rise in ME (p less than 0.005) and hypothalamic dopamine (p lessmore » than 0.005) content; these results are consistent with a dopamine-beta-hydroxylase inhibiting effect of cysteamine. No effect was observed on hypothalamic serotonin and 5-hydroxyindole-acetic acid content. Pineal N-acetyltransferase (NAT) activity was significantly higher (p less than 0.05) after cysteamine than after saline, but no statistically significant effect was observed on pineal melatonin content. The mechanism involved in the NAT rise is presumably not related to the known stimulatory effect of norepinephrine, which fell after cysteamine. It is suggested that cysteamine may act at an intracellular level, inhibiting NAT degradation, an effect demonstrated in vitro and thought to be related to a thiol:disulfide exchange mechanism.« less

The in vitro maintenance of clock genes expression within the rat pineal gland under standard and norepinephrine-synchronized stimulation.

PubMed

Andrade-Silva, Jéssica; Cipolla-Neto, José; Peliciari-Garcia, Rodrigo A

2014-01-01

Although the norepinephrine (NE) synchronization protocol was proved to be an important procedure for further modulating in vitro pineal melatonin synthesis, the maintenance of clock genes under the same conditions remained to be investigated. The aim of this study was to investigate the maintenance of the clock genes expression in pineal gland cultures under standard and NE-synchronized stimulation. The glands were separated into three experimental groups: Control, Standard (acute NE-stimulation), and NE-synchronized. The expression of Bmal1, Per2, Cry2, Rev-erbα, the clock controlled gene Dbp and Arylalkylamine-N-acetyltransferase were investigated, as well as melatonin content. No oscillations were observed in the expression of the investigated genes from the control group. Under Standard NE stimulation, the clock genes did not exhibit a rhythmic pattern of expression. However, in the NE-synchronized condition, a rhythmic expression pattern was observed in all cases. An enhancement in pineal gland responsiveness to NE stimulation, reflected in an advanced synthesis of melatonin was also observed. Our results reinforce our previous hypothesis that NE synchronization of pineal gland culture mimics the natural rhythmic release of NE in the gland, increasing melatonin synthesis and keeping the pineal circadian clock synchronized, ensuring the fine adjustments that are relied in the clockwork machinery. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Oligoastrocytoma

MedlinePlus

... Pineal Tumor Pituitary Tumor PNET Schwannoma 2016 WHO Classification Risk Factors Brain Tumor Facts Brain Tumor Dictionary ... Pineal Tumor Pituitary Tumor PNET Schwannoma 2016 WHO Classification Risk Factors Brain Tumor Facts Brain Tumor Dictionary ...

Oligodendroglioma

MedlinePlus

... Pineal Tumor Pituitary Tumor PNET Schwannoma 2016 WHO Classification Risk Factors Brain Tumor Facts Brain Tumor Dictionary ... Pineal Tumor Pituitary Tumor PNET Schwannoma 2016 WHO Classification Risk Factors Brain Tumor Facts Brain Tumor Dictionary ...

Vesicular Glutamate Transporter 2 Expression in the Rat Pineal Gland: Detailed Analysis of Expression Pattern and Regulatory Mechanism

NASA Astrophysics Data System (ADS)

Yoshida, Sachine; Hisano, Setsuji

Melatonin, a hormone secreted by the pineal gland, is closely related physiologically to circadian rhythm, sleep and reproduction, and also psychiatrically to mood disorders in humans. Under circadian control, melatonin secretion is modulated via nocturnal autonomic (adrenergic) stimulation to the gland, which expresses vesicular glutamate transporter (VGLUT) 1, VGLUT2 and a VGLUT1 splice variant (VGLUT1v), glutamatergic markers. Expression of VGLUT2 gene and protein in the intact gland has been reported to exhibit a rhythmic change during a day. To study VGLUT2 expression is under adrenergic control, we here performed an in vitro experiment using dispersed pineal cells of rats. Stimulation of either β-adrenergic receptor or cAMP production to the pineal cells was shown to increase mRNA level of VGLUT2, but not VGLUT1 and VGLUT1v. Because an ability of glutamate to inhibit melatonin production was previously reported in the cultured gland, it is likely that pineal VGLUT2 transports glutamate engaged in the inhibition of melatonin production.

Material translations in the Cartesian brain.

PubMed

Bassiri, Nima

2012-03-01

This article reexamines the controversial doctrine of the pineal gland in Cartesian psychophysiology. It argues initially that Descartes' combined metaphysics and natural philosophy yield a distinctly human subject who is rational, willful, but also a living and embodied being in the world, formed in the union and through the dynamics of the interaction between the soul and the body. However, Descartes only identified one site at which this union was staged: the brain, and more precisely, the pineal gland, the small bulb of nervous tissue at the brain's center. The pineal gland was charged with the incredible task of ensuring the interactive mutuality between the soul and body, while also maintaining the necessary ontological incommensurability between them. This article reconsiders the theoretical obligations placed on the pineal gland as the site of the soul-body union, and looks at how the gland was consequently forced to adopt a very precarious ontological status. The article ultimately questions how successfully the Cartesian human could be localized in the pineal gland, while briefly considering the broader historical consequences of the ensuing equivalence of the self and brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Primary rhabdomyosarcoma of the pineal gland.

PubMed

Lau, Steven K M; Cykowski, Matthew D; Desai, Shiv; Cao, Ying; Fuller, Gregory N; Bruner, Janet; Okazaki, Ian

2015-05-01

To report a case of primary rhabdomyosarcoma (RMS) of the pineal gland in an adult, as well as review the literature on this rare entity. The case is compared with previous reports of similar entities, with emphasis on this patient's characteristics and clinical presentation, investigations, and management. Diagnosis of primary RMS of the pineal gland was based on the presence of strap cells and multinucleated myotube-like structures, as well as tumor cell expression of skeletal muscle markers consistent with myogenic differentiation. Multimodality treatment was initiated based on pediatric protocols. Unfortunately, the disease progressed on treatment, and the patient survived only 5 months from diagnosis. Pineal RMS is a rare disease with poor prognosis. Optimal management is unknown but likely to involve aggressive multimodality therapy. Copyright© by the American Society for Clinical Pathology.

Le Sommeil et l’Age: de la Physiopathologie a la Therapeutique (Sleep and Age: From Physiopathology to Therapeutics)

DTIC Science & Technology

2000-08-01

the pineal gland , presents a - Sleep hygiene circadian rhythm with a maximal production at 02:00. It Sleep being sensible to each behavioral...widely used in sports and military - a calcification of the pineal gland , scopes to allow a better tolerance to sleep deprivation. It - a more intensive...the genetic expression level in the performance (Dinges & Broughton, 1989). However, suprachiasmatic nucleus and/or the pineal gland , this method can

History of the pineal region tumor.

PubMed

Mottolese, C; Szathmari, A

2015-01-01

The pineal gland has interested humans from millenniums. In this paper we review back in the history and the evolution of the pineal gland surgery. Originally, this surgery used to carry a high rate of morbidity and mortality. Nowadays the development of the anesthetic, radiological, surgical and intensive care techniques have been responsible of an improvement of the surgical results and better quality of life. It is always interesting to know from where we come. Copyright © 2014. Published by Elsevier Masson SAS.

Expression and cellular localization of the transcription factor NeuroD1 in the developing and adult rat pineal gland.

PubMed

Castro, Analía E; Benitez, Sergio G; Farias Altamirano, Luz E; Savastano, Luis E; Patterson, Sean I; Muñoz, Estela M

2015-05-01

Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and β-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The pineal gland, but not melatonin, is associated with the termination of seasonal testicular activity in an annual reproductive cycle in roseringed parakeet Psittacula krameri.

PubMed

Sengupta, Anamika; Kumar Maitra, Saumen

2006-01-01

The role of the pineal gland and its hormone melatonin in the regulation of annual testicular events was investigated for the first time in a psittacine bird, the roseringed parakeet (Psittacula krameri). Accordingly, the testicular responsiveness of the birds was evaluated following surgical pinealectomy with or without the exogenous administration of melatonin and the experimental manipulations of the endogenous levels of melatonin through exposing the birds to continuous illumination. An identical schedule was followed during the four reproductive phases, each characterizing a distinct testicular status in the annual cycle, namely, the phases of gametogenic quiescence (preparatory phase), seasonal recovery of gametogenesis (progressive phase), seasonal initiation of sperm formation (pre-breeding phase), and peak gametogenic activity (breeding phase). In each reproductive phase, the birds were subjected to various experimental conditions, and the effects were studied comparing the testicular conditions in the respective control birds. The study included germ cell profiles of the seminiferous tubules, the activities of steroidogenic enzymes 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and Delta(5)3beta-hydroxysteroid dehydrogenase (Delta(5)3beta- HSD) in the testis, and the serum levels of testosterone and melatonin. An analysis of the data reveals that the pineal gland and its hormone melatonin may play an inhibitory role in the development of the testis until the attainment of the seasonal peak in the annual reproductive cycle. However, in all probability, the termination of the seasonal activity of the testis or the initiation of testicular regression in the annual reproductive cycle appears to be the function of the pineal gland, but not of melatonin.

Jet Lag Disorder

MedlinePlus

... light signal is low, the hypothalamus tells the pineal gland, a small organ situated in the brain, to ... During daylight hours, the opposite occurs, and the pineal gland produces very little melatonin. You may be able ...

Pineal-adrenal-immune system relationship under thermal stress: effect on physiological, endocrine, and non-specific immune response in goats.

PubMed

Sejian, Veerasamy; Srivastava, Rajendra Swaroop

2010-12-01

The purpose of the investigation was to observe the pineal-adrenal-immune system relationships and their influence on non-specific immune response in female goats under short-term thermal stress. Six female goats had been exposed to 40°C and 60% relative humidity in the psychrometric chamber for 17 days. Blood samples were obtained on days 0 and 10 to establish control and thermal stress effects, respectively. Chemical adrenalectomy was achieved by injecting metyrapone (100 mg/kg body weight) followed by exogenous melatonin treatment (0.1 mg/kg body weight) from 11th to 17th day of experiment. Thermal stress significantly (P≤0.05) altered the physiological responses. Metyrapone and melatonin treatment significantly (P≤0.05) reduced the thermal-stress-induced increase in plasma concentrations of cortisol and corticosterone while significantly (P≤0.05) increased the plasma melatonin on days 11 and 17. Furthermore, these treatments significantly (P<0.05) increased the phagocytic activity of neutrophils as compared to both control and thermal exposure values from 11-17 days of experiment. The data generated from this study help us to understand the functional relationship between pineal, adrenal, and immune system, and how this relationship modifies the non-specific immune response for the well being of goats during thermal stress.

The association of pineal gland volume and body mass in obese and normal weight individuals: a pilot study.

PubMed

Grosshans, Martin; Vollmert, Christian; Vollstaedt-Klein, Sabine; Nolte, Ingo; Schwarz, Emanuel; Wagner, Xenija; Leweke, Markus; Mutschler, Jochen; Kiefer, Falk; Bumb, Jan Malte

2016-09-01

In obese individuals impaired sleep and neuroendocrine alterations such as melatonin deficits are associated with circadian rhythm disruption, altered circadian clock gene expression, and bright light at night. While the relation of pineal gland volume (PGV) and melatonin levels has recently been documented in humans, surprisingly little is known about the possible interference of the PGV and the pathophysiology of obesity in humans. We therefore compared the PGV of obese with non-obese individuals; both groups were matched by age and gender. Volumetric analyses were performed on the basis of 3 Tesla high resolution Magnetic Resonance Imaging (MRI). We found, that the PGV was significantly smaller in obese individuals than in lean controls (P=0.036). Moreover, PGV and waist-hip ratio showed a significant negative association in controls (P=0.018, r s =-0.602) whereas no association of both variables was found in obese individuals (P=0.856, r s =-0.051). Thus, the current pilot investigation suggests that pineal gland function, reflected by PGV might be involved in the energy homeostasis and pathophysiological mechanisms that contribute to the development and the maintenance of obesity in humans. Moreover, our data supports the notion that the replacement of melatonin deficits might be a novel strategy in the treatment of obesity.

Benign symptomatic glial cysts of the pineal gland: a report of seven cases and review of the literature.

PubMed Central

Klein, P; Rubinstein, L J

1989-01-01

Seven cases of clinically symptomatic benign glial cyst of the pineal gland are reported. The cysts' size ranged from 1.0-4.5 cm in diameter. They were characterised by a golden or, less frequently, brown-reddish proteinaceous or haemorrhagic fluid content. The cyst wall, up to 2 mm thick, consisted of clusters of normal pineal parenchymal cells, often compressed and distorted, surrounded by reactive gliotic tissue which sometimes contained Rosenthal fibres. The presenting clinical features included headache (6/7), signs of raised intracranial pressure, partial or complete Parinaud's syndrome (5/7), cerebellar deficits (2/7), corticospinal and corticopontine fibre (2/7) or sensory (1/7) deficits, and emotional disturbances (2/7). CT and MRI (in 2/7 cases) scans showed a hypodense or nonhomogeneous lesion in the region of the pineal gland, with or without contrast enhancement. Surgical excision resulted in complete clearance of the symptoms in 5/7 patients. The previous literature is reviewed and the clinicopathological correlations and the possible pathogenetic mechanisms are discussed. The need to distinguish this benign lesion from other mass lesions of the pineal region, in particular from pinealocytoma, is stressed. Images PMID:2677249

Sudden and Unexpected Death During Sexual Activity, Due to a Glial Cyst of the Pineal Gland.

PubMed

Barranco, Rosario; Lo Pinto, Sara; Cuccì, Maria; Caputo, Fiorella; Fossati, Francesca; Fraternali Orcioni, Giulio; Ventura, Francesco

2018-06-01

Cysts of the pineal gland are benign lesions. Often asymptomatic, in the majority of cases they are discovered incidentally during brain magnetic resonance imaging or autopsy. Sporadically, however, they may cause such symptoms as chronic headache, loss of consciousness, corticospinal and sensory impairment, and, in some cases, even sudden death. A 45-year-old woman, in apparently good health, collapsed and died suddenly, after reaching orgasm while engaged in sexual intercourse. According to the circumstantial account of her relatives, the woman suffered from severe headaches, which were exacerbated by certain types of physical strain, such as sexual activity. Postmortem examination revealed no external injuries or internal diseases except for a cystic lesion of the pineal gland. Microscopically, the wall of the cyst consisted of a layer of glial tissue surrounded by an area of pineal elements. A complete forensic approach concluded that the cause of death was fatal cardiorespiratory failure resulting from midbrain compression due to a nonneoplastic pineal gland cyst, exacerbated by sexual activity. In this case, the intracranial pressure increase, secondary to Valsalva maneuver during climax, may further aggravate compression on the brainstem, thus concurring to determine the death.

60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, B.W.; Chess, E.K.; Anderson, L.E.

Rats exposed for 3 weeks to uniform 60-Hz electric fields of 39 kV/m (effective field strength) failed to show normal pineal gland circadian rhythms in serotonin N-acetyl transferase activity and melatonin concentrations. The time required for recovery of the melatonin rhythm after cessation of field exposure was determined to be less than 3 days. The rapid recovery suggests that the overall metabolic competence of the pineal is not permanently compromised by electric-field exposure, and that the circadian rhythm effect may be neuronally mediated.

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

PubMed

Hammadur Rahaman, S K; Khandelwal, Deepak; Khadgawat, Rajesh; Kandasamy, Devasenathipathy; Bakhshi, Sameer

2018-03-15

Pineal gland lesions usually present with central precocious puberty. A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. He received chemotherapy followed by radiotherapy and responded well. CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

Supracerebellar Infratentorial Endoscopic and Endoscopic-Assisted Approaches to Pineal Lesions: Technical Report and Review of the Literature.

PubMed

Snyder, Rita; Felbaum, Daniel R; Jean, Walter C; Anaizi, Amjad

2017-06-09

The pineal gland has a deep central location, making it a surgeon's no man's land. Surgical pathology within this territory presents a unique challenge and an opportunity for employment of various surgical techniques. In modern times, the microsurgical technique has been competing with the endoscope for achieving superior surgical results. We describe two cases utilizing a purely endoscopic and an endoscopic-assisted supracerebellar infratentorial approach in accessing lesions of the pineal gland. We also discuss our early learning experience with these approaches.

Supracerebellar Infratentorial Endoscopic and Endoscopic-Assisted Approaches to Pineal Lesions: Technical Report and Review of the Literature

PubMed Central

Felbaum, Daniel R; Jean, Walter C; Anaizi, Amjad

2017-01-01

The pineal gland has a deep central location, making it a surgeon’s no man’s land. Surgical pathology within this territory presents a unique challenge and an opportunity for employment of various surgical techniques. In modern times, the microsurgical technique has been competing with the endoscope for achieving superior surgical results. We describe two cases utilizing a purely endoscopic and an endoscopic-assisted supracerebellar infratentorial approach in accessing lesions of the pineal gland. We also discuss our early learning experience with these approaches. PMID:28690962

Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries.

PubMed

Villano, J Lee; Propp, Jennifer M; Porter, Kimberly R; Stewart, Andrew K; Valyi-Nagy, Tibor; Li, Xinyu; Engelhard, Herbert H; McCarthy, Bridget J

2008-04-01

The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973-2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997-2001); and National Cancer Data Base (NCDB; 1985-2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060-9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%-86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest.

Photoperiodic inhibition of testicular development is mediated by the pineal gland in white-footed mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, P.G.; Boshes, M.; Zucker, I.

White-footed mice were maintained in short or long photoperiods from birth to 60 days of age (10 h vs. 14 h of light per day). Testes weights and spermatogenesis were substantially reduced in short daylengths. Pinealectomy at 5-7 days of age eliminated the suppressive effect of photoperiod on the reproductive system. However, testicular development was not retarded in intact males kept from 25 to 60 days of age in short daylengths. Exposure to short daylengths prior to 25 days of age contributes to photoperiodic inhibition of testicular development. Removal of the pineal gland did not consistently affect gonadal maturation inmore » long photoperiods. The pineal gland transduces the effects of short daylengths on reproductive development. Some effects of long daylengths on the neuroendocrine axis of white-footed mice may also be mediated by the pineal gland.« less

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiter, R.J.; Anderson, L.E.; Buschbom, R.I.

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats and the findings are generallymore » consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations. 15 refs., 1 fig., 1 tab.« less

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiter, R.J.; Anderson, L.E.; Buschbom, R.L.

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistentmore » with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.« less

The contribution of the pineal gland on daily rhythms and masking in diurnal grass rats, Arvicanthis niloticus.

PubMed

Shuboni, Dorela D; Agha, Amna A; Groves, Thomas K H; Gall, Andrew J

2016-07-01

Melatonin is a hormone rhythmically secreted at night by the pineal gland in vertebrates. In diurnal mammals, melatonin is present during the inactive phase of the rest/activity cycle, and in primates it directly facilitates sleep and decreases body temperature. However, the role of the pineal gland for the promotion of sleep at night has not yet been studied in non-primate diurnal mammalian species. Here, the authors directly examined the hypothesis that the pineal gland contributes to diurnality in Nile grass rats by decreasing activity and increasing sleep at night, and that this could occur via effects on circadian mechanisms or masking, or both. Removing the pineal gland had no effect on the hourly distribution of activity across a 12:12 light-dark (LD) cycle or on the patterns of sleep-like behavior at night. Masking effects of light at night on activity were also not significantly different in pinealectomized and control grass rats, as 1h pulses of light stimulated increases in activity of sham and pinealectomized animals to a similar extent. In addition, the circadian regulation of activity was unaffected by the surgical condition of the animals. Our results suggest that the pineal gland does not contribute to diurnality in the grass rat, thus highlighting the complexity of temporal niche transitions. The current data raise interesting questions about how and why genetic and neural mechanisms linking melatonin to sleep regulatory systems might vary among mammals that reached a diurnal niche via parallel and independent pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoperiod: Its importance as an impeller of pineal and seasonal reproductive rhythms

NASA Astrophysics Data System (ADS)

Reiter, R. J.

1980-03-01

A number of long day breeding rodents depend on seasonal changes in photoperiodic length to synchronize their breeding seasons with the appropriate time of the year. These relationships are particularly conspicuous in the Syrian hamster where day length is vitally important in determining periods of sexual activity and inactivity. The organ in the body whose activity is most closely attuned to the photoperiodic environment is the pineal gland. During periods of darkness the biochemical and secretory activity of the pineal is enhanced with the resultant production of antigonadotrophic principles which are strongly suppressive to reproductive physiology. In this manner, decreasing day lengths of the fall are involved with suppressing sexual capability in male and female hamsters. Throughout the winter months darkness (because of the shorter day lengths and the fact that hamsters remain underground in lightless burrows) holds the gonads in an atrophic condition and thereby prevents hamsters from breeding. As spring approaches the neuroendocrine reproductive axis becomes refractory to the inhibitory effects of darkness and the pineal gland and, as a consequence, the gonads recrudesce allowing the animals to successfully reproduce. The long days of the spring and summer serve to interrupt the refractory period so that when winter approaches shortening day lengths will again, by way of the pineal gland, induce gonadalinvolution. In this scheme both light and darkness are critically important in synchronizing the phases of the annual reproductive cycle of the hamster with the appropriate season of the year. Melatonin may be the pineal hormone which mediates the effects of darkness on reproductive physiology.

/sup 3/H-retinol derived photopigment in chick pineal membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallingford, J.; Zatz, M.

Pineal glands display a day-night rhythm in the synthesis and secretion of melatonin. Dispersed chick pinealocytes retain their ability to respond to light in vitro for at least a week. Pinealocytes incubated overnight with /sup 3/H-retinol in the dark incorporate radioactivity predominantly into retinyl esters. To identify the chick pineal photopigment, SDS-PAGE was performed on radiolabelled preparations of pinealocytes and (intraocularly injected) rat retina. When intact cells or membrane preparations of cultured cells were incubated with NaCNBH/sub 3/, in the dark, a single radioactive peak with an apparent molecular weight of 32,000 daltons was observed. Rat retina preparations revealed amore » major peak at approximately 40,000 daltons. Protease inhibitors were present in the workup, and radioactivity corresponding to the smaller peak from pineal was not observed in retina. There was no radioactive peak when NaCNBH/sub 3/ was omitted. When samples were boiled in SDS the radioactivity shifted to the origin. These data suggest a protein in pinealocyte membranes which binds retinoid via a Schiff's base. Exposure to light of deoxycholate solubilized pineal membranes reduced the radioactivity associated with the protein. These findings raise the possibility that this protein is the pinealocyte's photopigment. Photopigments smaller than those observed in mammals have been reported in invertebrates.« less

Non-24-Hour Sleep-Wake Rhythm Disorder and Melatonin Secretion Impairment in a Patient With Pineal Cyst

PubMed Central

Ferri, Lorenzo; Filardi, Marco; Moresco, Monica; Pizza, Fabio; Vandi, Stefano; Antelmi, Elena; Toni, Francesco; Zucchelli, Mino; Pierangeli, Giulia; Plazzi, Giuseppe

2017-01-01

We report the case of a 14-year-old girl with a wide non-compressive pineal cyst, associated with the inability to control her sleep-wake schedule. Actigraphic monitoring showed a 24-hour free-running disorder (tau 26.96 hours). A 24-hour serum melatonin curve assay, with concomitant video-polysomnographic and body-core temperature monitoring, was performed. Melatonin curve showed a blunted nocturnal peak, lower total quantity of melatonin, and prolonged melatonin secretion in the morning, with normal temperature profile and sleep parameters. Treatment with melatonin up to 14 mg at bedtime was initiated with complete realignment of the sleep-wake rhythm (tau 23.93 hours). The role of the pineal cyst in the aforementioned alteration of melatonin secretion and free-running disorder remains controversial, but our case supports the utility of monitoring sleep/wake, temperature, and melatonin rhythms in the diagnostic work-up of pineal cysts associated with free-running disorder. Citation: Ferri L, Filardi M, Moresco M, Pizza F, Vandi S, Antelmi E, Toni F, Zucchelli M, Pierangeli G, Plazzi G. Non-24-hour sleep-wake rhythm disorder and melatonin secretion impairment in a patient with pineal cyst. J Clin Sleep Med. 2017;13(11):1355–1357. PMID:28992833

7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates.

PubMed

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Vaudry, Hubert

2017-09-14

The brain synthesizes steroids de novo from cholesterol, which are called neurosteroids. Based on extensive studies on neurosteroids over the past thirty years, it is now accepted that neurosteroidogenesis in the brain is a conserved property across vertebrates. However, the formation of bioactive neurosteroids in the brain is still incompletely elucidated in vertebrates. In fact, we recently identified 7α-hydroxypregnenolone (7α-OH PREG) as a novel bioactive neurosteroid stimulating locomotor behavior in the brain of several vertebrates. The follow-up studies have demonstrated that the stimulatory action of brain 7α-OH PREG on locomotor behavior is mediated by the dopaminergic system across vertebrates. More recently, we have further demonstrated that the pineal gland, an endocrine organ located close to the brain, is a major site of the formation of bioactive neurosteroids. In addition to the brain, the pineal gland actively produces 7α-OH PREG de novo from cholesterol as a major pineal neurosteroid that acts on the brain to control locomotor rhythms. This review summarizes the identification, biosynthesis and mode of action of brain and pineal 7α-OH PREG, a new bioactive neurosteroid regulating locomotor behavior, across vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

[Pineal anlage tumor in a 8-month-old boy. The first case reported in Spanish language].

PubMed

Rodríguez-Velasco, Alicia; Ramírez-Reyes, Alma Griselda

2014-01-01

The pineal anlage tumor is a very infrequent malign neoplasm. Even though it has been documented in literature, it is not listed yet in the World Health Organization's last nervous system classification (2007). It is a primitive pineal tumor with neuroepithelial and ectomesenchyme differentiation. Due to its low frequency, the understanding of its biological behavior and a suitable treatment are incomplete. In a search performed in PubMed with the term pineal anlage tumor, only seven informed cases were identified between 1989 and 2011. An 8-month-old infant was brought to medical attention because he had a progressive enlargement of the cephalic perimeter, and convergent strabismus of two months of evolution. A pineal tumor was identified. The histology showed glial tissue, ganglia cells, pigmented neuroepithelium and striate muscle cells. A ventriculoperitoneal derivation was done to diminish hydrocephalic pressure and also to led the complete surgical resection. The patient was treated with two courses of chemotherapy with carboplatine, ifosfamide and mesna. One year after the treatment, the patient is asymptomatic. This is the first case reported in Spanish language. Given that it is a really infrequent tumor, it could be misdiagnosed as teratome, melanotic or mesoblastic medulloblastoma, or a melanotic neuroectodermal tumor of childhood (melanotic prognoma).

PECULIAIRITIES OF MELATONIN EFFECT ON CHONORHYTMIC ORGANIZATION OF KIDNEY ACID-REGULATING FUNCTION INFLUENCED BY NITROGEN MONOXIDE SYNTHESIS BLOCKADE UNDER CONDITIONS OF PINEAL GLAND HYPOFUNCTION.

PubMed

Semenenko, S; Tymofiychuk, I; Boreyko, L; Karatieieva, S; Slobodian, K

2017-10-01

The objective of research is to study the peculiarities of melatonin effect on chronorhythmic organization of the kidney acid-regulating function influenced by nitrogen monoxide (NO) synthesis blockade under conditions of pineal gland (PG) hypofunction. The experiments were conducted on 72 mature non-linear albino male rats with their body mass 0,15-0,18 kg. The animals were kept under vivarium conditions at a stable temperature and air humidity fed on a standard dietary intake. The control group included animals (n=36) kept under conditions of usual light regimen (12.00С:12.00Т) during 7 days. The experimental group included animals (n=36) injected with N-nitro-L-arginine (L-NNA) in the dose of 20 mg/kg during 7 days under conditions of continuous light (12.00С:12.00С) and melatonin in the dose of 0,5 mg/kg during 7 days simultaneously. On the 8th day the animals were exposed to 5% water load with heated to room temperature water supplied and the parameters of the kidney acid-regulating function under conditions of forced diuresis were investigated. Kidney functions in the control animals are subordinated to accurate circadian organization. Daily rhythms of the parameters of kidney acid-regulating functions reflect similar changes of the renal processes. Chronorhythmic transformations of the kidney acid-regulating functions in animals with blocked NO synthesis against continuous light and parallel injection of melatonin enable to suggest that NO synthesis blockade under conditions of melatonin correction reduces daily mean pH level as compared to the control. Although, it was higher than that in the animals with blocked NO synthesis against the ground of physiological function of the pineal gland, and animals with PG hypofunction under conditions of NO synthesis blockadeю Therefore, under conditions of L-NNA blockade of NO synthesis and injection of melatonin influenced by PG hypofunction chronorhythmic transformations of architectonics and phase structure of rhythms of the majority of parameters of the kidney acid-regulating function were found, which is an important diagnostic sign of exertion of adaptive possibilities on the border of transmission of adaptation into disadaptation, were detected.

Changes in concentrations of cortisol and melatonin in plasma, expression of synaptophysin, and ultrastructural properties of pinealocytes in goat kids in situations of stress due to early weaning: the effect of melatonin.

PubMed

Redondo, E; Franco, A; Garcia, A; Masot, A J

2010-06-01

To analyse the changes in some histo-physiological parameters of the pineal gland of goat kids in situations of stress due to early weaning, and the effect of exogenous treatment with melatonin. Twenty-four 6-day-old Verata goat kids were used; 12 suckled their dams throughout the study (non-weaned groups), and the other 12 were removed from their dams and fed a milk replacer (weaned groups). Six goat kids in each group were treated with melatonin, and the other six with double-distilled pyrogen-free water (Day 0). On Days 28-29, blood samples were collected at 0600, 1000, 1400, 1800, 2200, 0200 and 0600 hours, to determine concentrations of cortisol and melatonin in plasma. On Days 29 and 30, six animals per group (three at 1400 and three at 0200 hours, respectively) were subject to euthanasia and the weight of their pineal glands determined. The structural immunocytochemistry, morphometric analysis, ultrastructural analysis and immunotransmission electron microscopy of the pineal glands were established. Concentrations of cortisol in plasma were significantly higher in weaned than in non-weaned goat kids (p<0.05), and treatment with melatonin reduced the concentrations in weaned kids (p<0.05). Concentrations of melatonin in plasma showed a similar pattern in the four groups, with peak values at 0200 and troughs at 1400 hours. Mean concentrations of melatonin in plasma in weaned goat kids were significantly lower than those in the other groups (p<0.05). In weaned goat kids not treated with melatonin, the weight and volume of the pineal gland, and number of pinealocytes, were significantly lower when compared with those from non-weaned kids (p<0.05). Quantitative ultrastructural analysis of pinealocytes showed the relative volume of mitochondria, rough endoplasmic reticulum and Golgi complex was significantly lower in weaned than non-weaned goat kids (p<0.05); treatment with melatonin significantly increased these parameters in weaned kids. Taken together, these results indicate that treatment with melatonin in goat kids in situations of stress due to premature weaning could play an important role in the improvement of histo-physiological function of the pineal gland.

Effect of electric field exposure on melatonin and enzyme circadian rhythms in the rat pineal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, B.; Anderson, L.E.; Hilton, D.I.

The effects of chronic 30-day electric field exposure on pineal serotonin N-acetyl transferase (EC 2.1.15) activity as well as melatonin and 5-methoxy tryptophol (5-MTOL) concentrations in rats, were assessed.

Immunofluorescence reveals unusual patterns of labelling for connexin43 localized to calbindin-D28K-positive interstitial cells in the pineal gland.

PubMed

Tsao, D D; Wang, S G; Lynn, B D; Nagy, J I

2017-06-01

Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 μm) or as unusually large pools of Cx43 ranging up to 4-7 μm in diameter or length. These puncta and pools were highly concentrated in perivascular spaces, where they were associated with numerous cells devoid of labelling for markers of pinealocytes (e.g. tryptophan hydroxylase and serotonin), and where they were minimally associated with blood vessels and lacked association with resident macrophages. Astrocytes labelled for glial fibrillary acidic protein were largely restricted to the anterior pole of the pineal gland, where they displayed only fine and sparse Cx43-puncta along their processes. Labelling for Cx43 was localized largely though not exclusively to the somata and long processes of a subpopulation of perivascular interstitial cells that were immunopositive for calbindin-D28K. These cells were often located among dense bundles or termination areas of sympathetic fibres labelled for tyrosine hydroxylase or serotonin. The results indicate that interstitial cells form abundant gap junctions composed of Cx43, and suggest that gap junction-mediated intracellular communication by these cells supports the activities of pinealocytes. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Norepinephrine activates NF-κB transcription factor in cultured rat pineal gland.

PubMed

Villela, Darine; de Sá Lima, Larissa; Peres, Rafael; Peliciari-Garcia, Rodrigo Antonio; do Amaral, Fernanda Gaspar; Cipolla-Neto, José; Scavone, Cristóforo; Afeche, Solange Castro

2014-01-17

The circadian rhythm in mammalian pineal melatonin secretion is modulated by norepinephrine (NE) released at night. NE interaction with β1-adrenoceptors activates PKA that phosphorylates the transcription factor CREB, leading to the transcription and translation of the arylalkylamine-N-acetyltransferase (AANAT) enzyme. Several studies have reported the interplay between CREB and the nuclear factor-κB (NF-κB) and a circadian rhythm for this transcription factor was recently described in the rat pineal gland. In this work we studied a direct effect of NE on NF-κB activation and the role played by this factor on melatonin synthesis and Aanat transcription and activity. Cultured rat pineal glands were incubated in the presence of two different NF-κB inhibitors, pyrrolidine-dithiocarbamate or sodium salicylate, and stimulated with NE. Melatonin content was quantified by HPLC with electrochemical detection. AANAT activity was measured by a radiometric assay and the expression of Aanat mRNA was analyzed by real-time PCR. Gel shift assay was performed to study the NF-κB activation in cultured rat pineal glands stimulated by NE. Our results showed that the p50/p50 homodimer of NF-κB is activated by NE and that it has a role in melatonin synthesis, acting on Aanat transcription and activity. Here we present evidence that NF-κB is an important transcription factor that acts, directly or indirectly, on Aanat transcription and activity leading to a modulation of melatonin synthesis. NE plays a role in the translocation of NF-κB p50/p50 homodimer to the nucleus of pinealocytes, thus probably influencing the nocturnal pineal melatonin synthesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Biological functions of melatonin in relation to pathogenesis of oral lichen planus.

PubMed

Chaiyarit, Ponlatham; Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda

2017-07-01

Oral lichen planus (OLP) is considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Accumulated data support the involvement of cell-mediated immune dysfunction in the development of OLP. However, the connection between neuroendocrine system and oral immune response in OLP patients has never been clarified. Melatonin is considered as a major chronobiotic hormone produced mainly by the pineal gland. This gland is recognized as a regulator of circadian rhythm and a sensor in the immune response through the NF-kB transduction pathway. It was suggested that pineal-derived melatonin and extra-pineal melatonin synthesized at the site of inflamed lesion might play a role in inflammatory response. According to our immunohistochemical study, expression of melatonin could be detected in human oral mucosa. In addition, increased levels of melatonin were observed in inflamed oral mucosa of OLP patients. We hypothesize that chronic inflammation possibly induces the local biosynthesis of melatonin in inflamed oral mucosa. We also speculate that melatonin in oral mucosa may play a cytoprotective role through its anti-oxidative and anti-inflammatory properties. Moreover, melatonin may play an immunomodulatory role in relation to pathogenesis of OLP. Our hypothesis provides a new implication for upcoming research on the connection between circadian neuroendocrine network and immune response in oral mucosal compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of bioactive factors of the pineal gland on thymus function and cell composition of the bone marrow and spleen in mice of different age.

PubMed

Labunets, I F; Butenko, G M; Khavinson, V Kh

2004-05-01

The effects of factors from the pineal gland on the titer of thymic serum factor in the supernatant of 3-h thymus stroma cultures, number of stromal precursor fibroblasts and CD4+ cells in the bone marrow, and CD8+ cells in the spleens of adult and old CBA mice were studied in vitro. Epithalamin, Epithalon, and melatonin appreciably increased the titer of thymic serum factor in the supernatant of thymus stroma cultures from mice of different age and increased the percentage of CD4+ cells in the bone marrow suspension from old animals in vitro. The percentage of CD8+ lymphocytes decreased after incubation of splenic cells from old mice with melatonin. The percentage of bone marrow fibroblast precursor cells from adult and old mice did not appreciably change after incubation with the preparations.

Endoscopic Histologic Mapping of a Mixed Germ Pineal Tumor.

PubMed

Velásquez, Carlos; Rivero-Garvía, Mónica; Rivas, Eloy; Cañizares, María de Los Angeles; Mayorga-Buiza, María José; Márquez-Rivas, Javier

2016-11-01

The accurate histologic diagnosis of germ cell tumors in the pineal region is a keystone for determining the best treatment strategy and prognosis. This situation poses a challenge for the neuropathologist, considering the lack of a standarized procedure to obtain biopsy samples, which results in few and small specimens, which are not suitable for diagnosis. We report a case in which a pineal region mixed germ cell tumor was accurately diagnosed by performing histologic mapping through a dual burr-hole endoscopic approach. The technical pitfalls and other considerations necessary for obtaining an accurate diagnosis in this tumor subgroup are specified. In addition, the histologic analysis regarding the sampling technique used is described. The supraorbital frontal endoscopic approach enables the surgeon to perform histologic mapping of pineal region tumors, allowing standarization of the procedure used to obtain the specimens. This approach could result in a more accurate diagnosis, especially in mixed germ cell neoplasms. Copyright © 2016 Elsevier Inc. All rights reserved.

Castration and testosterone induced changes in the pinealocytes of roseringed parakeet, Psittacula krameri, during different phases of the annual testicular cycle.

PubMed

Maitra, S K; Dey, M

1994-08-01

The pinealocytes in male roseringed parakeets (Psittacula krameri) were studied following bilateral castration and/or therapeutic administration of testosterone during the preparatory (June-July), progressive (Nov.-Dec.), pre-breeding (Jan.-Feb.) and breeding (March-April) phases of the annual testicular cycle. The responses of the pineal to either treatment were found to be almost identical throughout the investigation. In each reproductive phase, the pineal appeared to be hypertrophied following castration and the effect was reversed by therapeutic administration of testosterone, while hormonal treatment to the intact parakeets induced regressive changes in the pinealocytes. Collectively, the results of the current study support the hypothesis that the testis through its hormone testosterone exerts inhibitory influences on the activity of pineal, and may thus be considered as being involved in the determination of an inverse relationship between the pineal and the testis during the annual cycle of free-living parakeets.

Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland

USDA-ARS?s Scientific Manuscript database

The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a comp...

Interleukin-1 β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study.

PubMed

Herman, A P; Bochenek, J; Skipor, J; Król, K; Krawczyńska, A; Antushevich, H; Pawlina, B; Marciniak, E; Tomaszewska-Zaremba, D

2015-01-01

The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression.

A promoter polymorphism in the monoamine oxidase A gene is associated with the pineal MAOA activity in Alzheimer's disease patients.

PubMed

Wu, Ying-Hui; Fischer, David F; Swaab, Dick F

2007-09-05

Monoamine oxidase A (MAOA) is involved in the pathogenesis of mood disorders and Alzheimer's disease (AD). MAOA activity and gene expression have been found to be up-regulated in different brain areas of AD patients, including the pineal gland. Increased pineal MAOA activity might contribute to the reduced pineal melatonin production in AD. A promoter polymorphism of a variable number tandem repeats (VNTR) in the MAOA gene shows to affect MAOA transcriptional activity in vitro. Here we examined in 63 aged controls and 44 AD patients the effects of the MAOA-VNTR on MAOA gene expression and activity in the pineal gland as endophenotypes, and on melatonin production. AD patients carrying long MAOA-VNTR genotype (consisting of 3.5- or 4-repeat alleles) showed higher MAOA gene expression and activity than the short-genotyped (i.e., 3-repeat allele) AD patients. Moreover, the AD-related up-regulation of MAOA showed up only among long-genotype bearing subjects. There was no significant effect of the MAOA-VNTR on MAOA activity or gene expression in controls, or on melatonin production in both controls and AD patients. Our data suggest that the MAOA-VNTR affects the activity and gene expression of MAOA in the brain of AD patients, and is involved in the changes of monoamine metabolism.

Interleukin-1β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study

PubMed Central

Herman, A. P.; Bochenek, J.; Skipor, J.; Król, K.; Krawczyńska, A.; Antushevich, H.; Pawlina, B.; Marciniak, E.; Tomaszewska-Zaremba, D.

2015-01-01

The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression. PMID:26339621

Medial posterior choroidal artery territory infarction associated with tumor removal in the pineal/tectum/thalamus region through the occipital transtentorial approach.

PubMed

Saito, Ryuta; Kumabe, Toshihiro; Kanamori, Masayuki; Sonoda, Yukihiko; Mugikura, Shunji; Takahashi, Shoki; Tominaga, Teiji

2013-08-01

Damage to the deep venous system, occipital lobe, and/or corpus callosum is well known to cause complications associated with the occipital transtentorial approach (OTA), but ischemic complications are not well documented. The authors investigated the high incidences of ischemic complications associated with removal of pineal/tectal/thalamic tumors through the OTA. Clinical records of 29 patients who underwent 31 surgeries using the OTA from December 2001 to May 2011 were retrospectively studied. Tumor locations were the pineal/tectal/thalamic region for 19, cerebellum for 7, and medial temporal lobe for 3. Postoperative diffusion-weighted magnetic resonance images obtained within 72 h after surgery detected infarction in the tectal/splenial/thalamic region, presumably representing the medial posterior choroidal artery (MPChA) territory, in 10 patients. All these patients had tumor in the pineal/tectal/thalamic region. Deteriorated or newly developed eye symptoms including vertical gaze palsy tended to persist in these patients compared to those without ischemic complications. A relatively high incidence of MPChA territory infarction was associated with removal of tumors in the pineal/tectal/thalamic region through the OTA. Eye symptoms often occurred post-surgery and tended to persist in these patients. Neurosurgeons must be aware of the possibility of MPChA territory infarction to further increase the safety of the OTA. Copyright © 2012 Elsevier B.V. All rights reserved.

Fatigue Assessment in Camp Mirage CC130 Aircrew: Recommendations for Pharmacologic Intervention

DTIC Science & Technology

2004-02-20

naturally occurring hormone synthesized by the pineal gland from the precursor amino acid tryptophan (4). In pharmacologic doses, melatonin has a large...the intake of melatonin or placebo. Adv Pineal Res 1991; 5: 303-09. 10. Pang SF, Pang CS, Poon AM, Lee PP, Liu ZM, Shiu SY. Melatonin: a chemical

Papillary tumor of the pineal region: Case report and review of the literature.

PubMed

Cañizares Méndez, María de Los Ángeles; Amosa Delgado, Manuel; Álvarez Salgado, Juan Antonio; Villaseñor Ledezma, Jorge Javier; Capilla Cabezuelo, Elena; Díaz Crespo, Francisco

2018-04-22

Papillary tumor of the pineal region is a rare neuroepithelial tumor characterized by papillary architecture and epithelial cytology, immunopositivity for cytokeratin and ependymal differentiation. It is considered grade II-III by the World Health Organization and was first described by Jouvet in 2003. We present a 34-year-old male with headaches, blurred vision and normal examination. Radiological study showed a nodulocystic lesion in the pineal region compatible with pineocytoma. Surgery was performed using an infratentorial supracerebellar approach, finding a cystic tumor in the quadrigeminal cistern which was completely resected. Histopathology reported a papillary tumor of the pineal region. The patient made good progress without adjuvant therapy, and after 57 months of follow-up he remained asymptomatic and free of recurrence. A review of the literature was performed to collect all the cases published with gross total resection and no complementary treatment. In conclusion, there is still much to be learned about the pathogenesis, prognosis and management of this tumor. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

[Effect of moxibustion on quantity of pinealocytes and pineal HSP 70 expression in subacute aging rats].

PubMed

Liang, Xin; Zhong, Yu

2011-08-01

To study the mechanism of moxibustion in postponing the process of aging. Thirty Wistar rats were equally randomized into control, model and moxibustion groups. The subacute aging model was established by hypodermic injection of 25% D-galactose (125 mg/kg). Moxibustion was applied to bilateral "Shenshu" (GV 23) and "Pishu" (GV 20) once everyday for 6 weeks. After slicing, the pineal gland tissue was stained with HE and insitu hybridization methods respectively for detecting the quantity of pinealocytes and the expression of heat shock protein (HSP 70). Compared with the control group, both the quantity of pinealocytes and the expression of HSP 70 in the pineal gland in the model group were downregulated significantly (P < 0.001, P < 0.01). Compared with model group, the quantity of pinealocytes and of HSP 70 mRNA in the pineal gland of moxibustion group were upregulated significantly (P < 0.01, P < 0.05). Moxibustion can suppress aging induced decrease of pinealocyte number and HSP 70 expression in subacute aging rats, which may contribute to its effect in postponing aging.

Melatonin and pineal gland peptides are able to correct the impairment of reproductive cycles in rats.

PubMed

Arutjunyan, Alexander; Kozina, Ljudmila; Milyutina, Yulia; Korenevsky, Andrew; Stepanov, Michael; Arutyunov, Vladimir

2012-12-01

Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging. The investigation of epithalamine (a polypeptide preparation from the bovine pineal gland) effect on circadian rhythms disturbed by the neurotoxic compound DMH has shown a recovery of the diurnal dynamics of NE in MPA. In addition, NE was found to decrease from 9:30 till 11 o'clock, Circadian Time (CT), which was typical of control animals. Epitalon (Ala-Glu-Asp-Gly) proved to be more effective in ME-Arc. This peptide prevents the xenobiotic caused disturbance of DA diurnal rhythm, keeping this metabolite low at 5 o'clock (CT) with it having increased by 11 o'clock (CT). The data obtained suggest that the pineal gland is important for the circadian signal normalization needed for gonadoliberin surge on the day of proestrus. Melatonin and peptides of the pineal gland can be considered as effective protectors of female reproductive system from xenobiotics and premature aging.

The expression of Per1 and Aa-nat genes in the pineal gland of postnatal rats.

PubMed

Wongchitrat, Prapimpun; Govitrapong, Piyarat; Phansuwan-Pujito, Pansiri

2012-12-01

The circadian rhythm of melatonin synthesis is controlled by the master clock, suprachiasmatic nucleus (SCN). The level of melatonin changes throughout the aging process. The SCN's rhythm is driven by autoregulatory feedback loop composed of a set of clock genes families and their corresponding proteins. The Period (Per1), one of clock gene develops gradually during postnatal ontogenesis in the rat SCN and is also expressed in the pineal gland. It is of interest to study the relationship between the postnatal development of Per1 and Aa-nat, genes that produce the rate-limiting enzyme in melatonin synthesis, in the pineal. Daily profiles of mRNA expression of Per1 and Aa-nat were analyzed in the pineal gland of pups at postnatal ages 4 (P4), P8, P16 and P32, at puberty age of 6 weeks; and in 8 week-old adult rats by real-time PCR. As early as P4, Per1 and Aa-nat mRNAs were expressed and existed at relatively high levels during the nighttime. They gradually increased until puberty and decreased at 8 weeks of age. Additionally, the nocturnal changes of Per1 and Aa-nat mRNA levels in the rat pineal gland from P4 to adults were strongly correlated at r = 0.97 (p < 0.01). The present data indicate that there is a close relationship between the expression pattern of Per1 and that of melatonin synthesis during the development of postnatal rats.

Pineal control of the dopamine D2-receptor gene and dopamine release in the retina of the chicken and their possible relation to growth rhythms of the eye.

PubMed

Ohngemach, S; Feldkaemper, M; Schaeffel, F

2001-09-01

Retinal dopamine (DA) and the DA D2-receptor have been implicated in the development of "deprivation myopia", induced by frosted eye occluders. We have studied the changes in D2-mediated dopaminergic transmission in the retina, their possible relations to eye growth rhythms and myopia, and their control by the pineal gland. (1) We found that the sensitivity of eye growth to retinal image degradation varied over the day. Intermittent periods of normal vision inhibited deprivation myopia more if they occurred in the evening than in the morning. (2) Diurnal growth rhythms in both eyes interacted even though it was previously shown that both deprivation myopia and the accompanying changes in retinal DA release can be monocularly induced. (3) The D2-receptor mRNA concentration in the retina showed no systemic diurnal changes and was not affected by deprivation myopia, but was increased after 2 days in darkness. Since DA release varies over the day, the gain of dopaminergic transmission may also vary, which could explain the observation described in (1) above. (4) Depletion of retinal DA by intravitreal application of reserpine, which lowers DA content severely, had little effect on D2-receptor mRNA concentration. (5) Selective illumination of the pineal gland reduced the D2-receptor mRNA content in the retina to a similar level to full illumination, indicating that the pineal gland controls the D2-receptor mRNA content in the retina. The pineal also controlled DA release in the retina. These results show that the pineal has a surprisingly large influence on both the retinal DA receptor gene transcription and DA release. It can probably control the gain of dopaminergic transmission in the retina and deprivation myopia and mediate the interactions of the growth rhythms in both eyes.

A Long Term Follow Up After Radiosurgery Of Papillary Tumour Of The Pineal Region (Ptpr): Two Cases Report And Review Of The Literature.

PubMed

Fernández-Mateos, Cecilia; Martinez, Roberto; Vaquero, Jesús

2018-05-19

Tumours of the pineal region are rare in adulthood, accounting for approximately 1% of intracranial neoplasms in this age range. Because of their rarity, it has proven to be difficult to establish the optimal therapy. Furthermore, microsurgical total resection in this eloquent location is associated with not low rates of morbidity. We described two patients diagnosed of papillary tumours of the pineal region (PTPR) by stereotactic biopsy and referred for gamma knife radiosurgery after shunting for hydrocephalus. We are reporting a long-term follow up of 15 and 20 years respectively, showing a good response to the treatment. Copyright © 2018. Published by Elsevier Inc.

The concept of the immune-pineal axis tested in patients undergoing an abdominal hysterectomy.

PubMed

de Oliveira Tatsch-Dias, Mirella; Levandovski, Rosa Maria; Custódio de Souza, Izabel Cristina; Gregianin Rocha, Marcelo; Magno Fernandes, Pedro Augusto Carlos; Torres, Iraci L S; Hidalgo, Maria Paz L; Markus, Regina P; Caumo, Wolnei

2013-01-01

Activation of the immune-pineal axis induces a transient reduction in nocturnal melatonin in the plasma during the proinflammatory phase of an innate immune response to allow the proper migration of leukocytes to the lesion site. This transient reduction should be regulated by inflammatory mediators, which are responsible for the fine-tuning of the process. In the present study, we measured the pre- and postoperative serum concentrations of melatonin, tumor necrosis factor (TNF) and cortisol in women who underwent an elective hysterectomy and correlated the variation in melatonin with postoperative pain. We evaluated 12 women who had an abdominal hysterectomy. Blood was collected at 10.00 and 22.00 h 1 week and 1 day before the surgery, on the 1st and 2nd days after the surgery and at 22.00 h on the day of the surgery. On the night after the surgery, there was no melatonin detected at 22.00 h. High TNF levels were accompanied by a lower nocturnal melatonin output, higher postoperative pain according to a visual analog scale and the request of higher doses of analgesics. In addition, low cortisol levels were accompanied by a lower nocturnal melatonin output. Our results confirm that the same antagonistic pattern between TNF and glucocorticoids observed in cultured pineal glands also occurs in humans. This integrative pattern suggests that the cross talk between the immune and endocrine system orchestrates longitudinal changes in pineal activity, reinforcing the hypothesis of an immune-pineal axis. Copyright © 2013 S. Karger AG, Basel.

Lateral supracerebellar infratentorial approach for microsurgical resection of large midline pineal region tumors: techniques to expand the operative corridor.

PubMed

Kulwin, Charles; Matsushima, Ken; Malekpour, Mahdi; Cohen-Gadol, Aaron A

2016-01-01

Pineal region tumors pose certain challenges in regard to their resection: a deep surgical field, associated critical surrounding neurovascular structures, and narrow operative working corridor due to obstruction by the apex of the culmen. The authors describe a lateral supracerebellar infratentorial approach that was successfully used in the treatment of 10 large (> 3 cm) midline pineal region tumors. The patients were placed in a modified lateral decubitus position. A small lateral suboccipital craniotomy exposed the transverse sinus. Tentorial retraction sutures were used to gently rotate and elevate the transverse sinus to expand the lateral supracerebellar operative corridor. This approach placed only unilateral normal structures at risk and minimized vermian venous sacrifice. The surgeon achieved generous exposure of the caudal midline mesencephalon through a "cross-court" oblique trajectory, while avoiding excessive retraction on the culmen. All patients underwent the lateral approach with no approach-related complication. The final pathological diagnoses were consistent with meningioma in 3 cases, pilocytic astrocytoma in 3 cases, intermediate grade pineal region tumor in 2 cases, and pineoblastoma in 2 cases. The entire extent of these tumors was readily reachable through the lateral supracerebellar route. Gross-total resection was achieved in 8 (80%) of the 10 cases; in 2 cases (20%) near-total resection was performed due to adherence of these tumors to deep diencephalic veins. Large midline pineal region tumors can be removed through a unilateral paramedian suboccipital craniotomy. This approach is simple, may spare some of the midline vermian bridging veins, and may be potentially less invasive and more efficient.

Anterior interhemispheric transsplenial approach to pineal region tumors: anatomical study and illustrative case.

PubMed

Yağmurlu, Kaan; Zaidi, Hasan A; Kalani, M Yashar S; Rhoton, Albert L; Preul, Mark C; Spetzler, Robert F

2018-01-01

Pineal region tumors are challenging to access because they are centrally located within the calvaria and surrounded by critical neurovascular structures. The goal of this work is to describe a new surgical trajectory, the anterior interhemispheric transsplenial approach, to the pineal region and falcotentorial junction area. To demonstrate this approach, the authors examined 7 adult formalin-fixed silicone-injected cadaveric heads and 2 fresh human brain specimens. One representative case of falcotentorial meningioma treated through an anterior interhemispheric transsplenial approach is also described. Among the interhemispheric approaches to the pineal region, the anterior interhemispheric transsplenial approach has several advantages. 1) There are few or no bridging veins at the level of the pericoronal suture. 2) The parietal and occipital lobes are not retracted, which reduces the chances of approach-related morbidity, especially in the dominant hemisphere. 3) The risk of damage to the deep venous structures is low because the tumor surface reached first is relatively vein free. 4) The internal cerebral veins can be manipulated and dissected away laterally through the anterior interhemispheric route but not via the posterior interhemispheric route. 5) Early control of medial posterior choroidal arteries is obtained. The anterior interhemispheric transsplenial approach provides a safe and effective surgical corridor for patients with supratentorial pineal region tumors that 1) extend superiorly, involve the splenium of the corpus callosum, and push the deep venous system in a posterosuperior or an anteroinferior direction; 2) are tentorial and displace the deep venous system inferiorly; or 3) originate from the splenium of the corpus callosum.

3D highly heterogeneous thermal model of pineal gland in-vitro study for electromagnetic exposure using finite volume method

NASA Astrophysics Data System (ADS)

Cen, Wei; Hoppe, Ralph; Lu, Rongbo; Cai, Zhaoquan; Gu, Ning

2017-08-01

In this paper, the relationship between electromagnetic power absorption and temperature distributions inside highly heterogeneous biological samples was accurately determinated using finite volume method. An in-vitro study on pineal gland that is responsible for physiological activities was for the first time simulated to illustrate effectiveness of the proposed method.

The Inhibition of P$sup 32$ Capture in the Ovaries and Uterus of White Rats Following the Administration of Pineal Hormone; L'INHIBITION DE LA CAPTATION DU PHOSPHORE P$sup 32$ CHEZ LES RATS ALBINOS AU NIVEAU DES OVARIES ET DE L'UTERUS APRES L'ADMINISTRATION DE L'EPIPHYSEHORMONE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milcou, S.M.; Serban, Al.M.D. et al.

A study was made in the rat of the modifications in the rate of P/sup 32/ uptake by the ovaries and uterus following the administration of pineal hormone. A dose of 10 mu c of P/sup 32/ was injected intraperitoneally in nubile and nonnubile female rats which had received pineal hormone for ten days. The animals were sacrificed after 4 and 24 hours. The results showed that the rate of P/sup 32/ uptake was reduced in the ovaries and uterus. Antuitrin S and pinea1 hormone were injected into non-nubile rats to study a possible inhibition of gonadotropin by this hormone.more » Gonadotropin causes an increase in P/sup 32/ uptake by the ovary and uterus with a progressive tendency for the first 24 hours. Pineal hormone causes a decrease in the degree of P/sup 32/ uptake produced by the gonadotropin. (J.S.R.)« less

Antioxidant properties of geroprotective peptides of the pineal gland.

PubMed

Kozina, L S; Arutjunyan, A V; Khavinson, V Kh

2007-01-01

It was shown that peptide preparations from the pineal gland (epithalamin and epitalon) possess antioxidant properties exceeding in some cases the effects of the well-known scavenger of reactive oxygen species (ROS), the melatonin, which is also produced by the pineal gland. The methods used in our experiments in old rats included determination of total antioxidant and antiradical activities, as well as those of antioxidant enzymes (superoxide dismutase=SOD, glutathione peroxidase, glutathione-S-transferase, etc.) in blood serum, liver and brain. It has been revealed that epithalamin (polipeptide preparation from bovine brain) and its active fragment, epitalon (Ala-Glu-Asp-Gly) along with their ability to stimulate melatonin production, have an antioxidant mechanism that is quite different from the action of melatonin. Epithalamin can be more beneficial than melatonin because the former not only produces direct antioxidant effects, but also is able to stimulate the expression of SOD, ceruloplasmin and other antioxidant enzymes. The possibility of oxidation chains by their interaction with different ROS by means of binding of transition metals (Fe(2+)) cannot also be excluded. Thus, the results of our experiments testify that the pineal gland peptides enhance the antioxidant defense system, which can contribute to their geroprotective properties.

Regulation of period 1 expression in cultured rat pineal

NASA Technical Reports Server (NTRS)

Fukuhara, Chiaki; Dirden, James C.; Tosini, Gianluca

2002-01-01

The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE - or forskolin - stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal. Copyright 2002 S. Karger AG, Basel.

Pineal gland as an endocrine gravitational lunasensor: manifestation of moon-phase dependent morphological changes in mice.

PubMed

Gerasimov, A V; Kostyuchenko, V P; Solovieva, A S; Olovnikov, A M

2014-10-01

We found that some morphological properties of the pineal gland and submandibular salivary gland of mice are significantly distinct at the new and full moon. We suppose that the differences are initiated by the displacements of the electron-dense concretions in the secretory vesicles of pinealocytes. This presumably occurs under the influence of the gravitational field, which periodically changes during different phases of the moon. It seems that the pinealocyte is both an endocrine and gravisensory cell. A periodic secretion of the pineal gland probably stimulates, in a lunaphasic mode, the neuroendocrine system that, in turn, periodically exerts influence on different organs of the body. The observed effect probably serves, within the lifelong clock of a brain, to control development and aging in time.

All genes encoding enzymes participating in melatonin biosynthesis in the chicken pineal gland are transcribed rhythmically.

PubMed

Adamska, I; Marhelava, K; Walkiewicz, D; Kedzierska, U; Markowska, M; Majewski, P M

2016-08-01

Our recent research on the pineal gland of young chickens confirmed that three genes encoding enzymes involved in pineal melatonin biosynthesis, tryptophan hydroxylase 1 (Tph1), arylalkylamine-N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), are transcribed rhythmically under light:dark (L:D) 12:12 conditions in vivo. Additionally, in the pineal gland of maturing chickens, the dopa decarboxylase (Ddc) gene is transcribed rhythmically at a specific stage of the developmental process. Therefore, the aim of the present study was to verify whether all of these genes are transcribed rhythmically in vivo under constant darkness (D:D) and in pinealocyte cultures under both L:D and D:D. Experiments were performed on chickens maintained under L:D 12:12 conditions. Chickens at 15 days of age were divided into two groups; chickens from the first group remained under the same conditions, whereas those from the second group were kept in darkness. Subsequently, 16-day-old animals were sacrificed every 2 hours over a 24-h period. For the in vitro experiments, 16-day-old chickens were sacrificed at ZT 6, and their pineal glands were isolated. Pineal cultures were maintained for up to two days in L:D conditions. Then, the pinealocyte cultures were divided into two groups: the first remained under L:D conditions, whereas the second was transferred to D:D conditions. Pinealocytes were subsequently collected every 2 hours over a 24-h period. Transcription was evaluated using the RT-qPCR method, and the rhythm percentage was calculated through Cosinor analysis. The mRNA levels of all genes examined were rhythmic under all conditions. Moreover, in silico analysis of the promoters of all of the genes examined revealed the presence of enhancer box sequences in all of the promoters as well as DBP/E4BP4 binding elements in the promoters of Tph1 and Asmt. This suggests that these genes may all be regulated transcriptionally by the molecular clock mechanism and may be considered clock as controlled genes.

Modulating effects of epithalamin and epithalon on the functional morphology of the spleen in old pinealectomized rats.

PubMed

Khavinson, V K; Konovalov, S S; Yuzhakov, V V; Popuchiev, V V; Kvetnoi, I M

2001-11-01

Immunohistochemical and morphometric analysis showed that epithalamin and epithalon produced similar effects on the functional morphology of the spleen in pinealectomized rats. Both peptides prevented hyperplasia of lymphoid cells in follicular germinative centers induced by pinealectomy and potentiated the decrease in extramedullary hemopoiesis. These findings confirm the data on functional relationships between the pineal gland and immune system. The effects of epithalamin and epithalon on cell and tissue homeostasis in the spleen of old pinealectomized rats can be regarded as a manifestation of the general regulatory effect of these peptides.

Comparison of Light Emitting Diodes (LED) and Fluorescent Light on Suppression of Pineal Melatonin in the Rat

NASA Technical Reports Server (NTRS)

Winget, Charles M.; Heeke, D. S.; Holley, D. C.; Mele, G.; Brainard, G. C.; Hanifin, J. P.; Rollag, M. D.; Savage, Paul D. (Technical Monitor)

1997-01-01

To validate a novel LED array for use in animal habitat lighting by comparing its effectiveness to cool-white fluorescent (CWF) lighting in suppressing pineal gland melatonin. Male Sprague-Dawley rats, 175-200 g, were maintained under control conditions for 2 weeks (food and water ad lib, 12L: 12D CWF, 18 uW/square cm). Dark adapted animals (animals before lights on) were exposed to 5 min of LED or CWF light of similar spectral power distribution. Two groups of rats (LED vs. CWF) were compared at 5 light intensities (100, 40, 1, 1.0, and 0. 1 lux). A control group was placed into the exposure apparatus but not exposed to light. After exposure, pineal glands were rapidly removed and assayed for melatonin by RIA. Results. The dark-exposed control groups matched with the 5 intensity groups (100, 40, 10, 1.0, and 0.1 lux) showed mean + SEM pineal melatonin values of 1167 +/- 136, 1569 +/- 126, 353 +/- 34, 650 +/- 124, and 464 +/- 85, pg/ml respectively. The corresponding CWF exposure data were 393 1 41, 365 +34, 257 +/- 13, 218 +/- 42, and 239 +/- 71 pg/ml, respectively. Corresponding LED exposure data were 439 +/- 25, 462 +/- 50, 231 +/- 6, 164 +/- 12, and 158 +/- 12 pg/ml, respectively. Rats exposed to both experimental light conditions at all illuminances studied showed significant melatonin suppression (p less than 0.01, ANOVA). In no case was the melatonin suppression induced by LED illuminance significantly different from the melatonin suppression elicited by the same intensity of CWF light. The results show that a novel LED light source can suppress pineal melatonin equal to that of a conventional CWF light source.

Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review.

PubMed

Taramasso, L; Boisson-Dupuis, S; Garrè, M L; Bondi, E; Cama, A; Nozza, P; Morana, G; Casanova, J L; Marazzi, M G

2014-11-01

Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

The Role of Glucocorticoids and Neuroinflammation in Mediating the Effects of Stress on Drug Abuse

DTIC Science & Technology

2013-10-01

addiction. In the second year of this project, we made pivotal discoveries in how stress sensitizes the pro-inflammatory effects of methamphetamine ...immunophenotypic and functional characteristics. J Neurosci Methods 151, 121- 130. Krasnova et al., 2009. Methamphetamine toxicity and messengers of death...Tocharus et al., 2010. Melatonin attenuates methamphetamine -induced overexpression of pro- inflammatory cytokines in microglial cell lines. J Pineal Res

Physiological and Biochemical Mechanisms of Lifespan Regulation in Rats Kept Under Various Light Conditions.

PubMed

Khizhkin, Evgeniy A; Ilukha, Victor A; Vinogradova, Irina A; Uzenbaeva, Lyudmila B; Ilyina, Tatiana N; Yunash, Victoria D; Morozov, Artem V; Anisimov, Vladimir N

2017-01-01

The present study was aimed to identify how age-related changes in some physiological and biochemical systems are related to changes in the life span of rats with long-term pineal gland hypo- and hyperfunction induced by constant light and constant darkness, respectively. At the age of 25 days the rats were randomly divided into 3 groups: standard light/dark regimen (LD), constant light (LL) and constant darkness (DD). Age-related Antioxidant System (AOS) changes in liver tissues, alteration of immunoreactivity in blood smears were investigated, pubescence and lifespan of the animals were determined. Modification of the level of melatonin synthesis induced by constant light results in interrelated rearrangements in the functioning of the investigated physiological systems. Elevated activity of the antioxidant system extends the lifespan, while at the same time slowing down pubescence and altering the morpho-functional properties of leukocytes in blood. The absence of light/dark alternation (constant light and constant darkness) affects only those physiological indices that follow the organism's circadian rhythms (Activity of Antioxidant Enzymes (AOE), levels of individual immune system cell types), whereas changes in the parameters not governed by circadian fluctuations (vitamin concentrations, pubescence, and aging) depend on the level of melatonin produced by the pineal gland.

This pineal gland does not mediate phase shifts in the disc shedding rhythm of the rat retina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldman, A.I.

Albino rats were subjected to pinealectomy, superior cervical ganglionectomy, or the appropriate sham preparation and were placed in lighting conditions so that light onset was advanced by 10 hr. After 6 days of this regimen, all animals exhibited a complete shift in their outer segment disc shedding rhythm, indicating that the pineal gland is not a factor in mediating such a shift.

A model for the neural control of pineal periodicity

NASA Astrophysics Data System (ADS)

de Oliveira Cruz, Frederico Alan; Soares, Marilia Amavel Gomes; Cortez, Celia Martins

2016-12-01

The aim of this work was verify if a computational model associating the synchronization dynamics of coupling oscillators to a set of synaptic transmission equations would be able to simulate the control of pineal by a complex neural pathway that connects the retina to this gland. Results from the simulations showed that the frequency and temporal firing patterns were in the range of values found in literature.

Transventricular Transvelar Approach to Trochlear Nerve Schwannoma: Novel Technique to Lesions of Inferior Pineal Region.

PubMed

Farrokhi, Majid Reza; Ghaffarpasand, Fariborz; Taghipour, Mousa; Derakhshan, Nima

2018-06-01

The schwannoma of the trochlear nerve is rare and originates mostly from the distal parts in the interpeduncular cistern. A lesion on the proximal segment in the inferior pineal region is extremely rare. Because of the rarity of the disease, the surgical approach to this region for the resection of trochlear nerve schwannoma has not been well documented in the literature. We herein describe a novel approach to successfully resect the trochlear nerve schwannoma. A 12-year-old boy presented with occipital headache, abnormal gait, and disturbed conjoined eye movement. He was diagnosed with a lesion in the inferior pineal region compressing the superior medullary velum into the roof of the fourth ventricle. A bilateral midline suboccipital craniotomy was performed, and the fourth ventricle was exposed. The lesion was approached through the fourth ventricle superior medullary velum (transventricular transvelar approach). The lesion was totally resected, and his histopathology examination revealed trochlear schwannoma. The patient's symptoms resolved, and he had no recurrence at 12-year follow-up with normal eye movement and vision. The transventricular transvelar approach is feasible and safe to treat a lesion of the lower part of the pineal region being pushed through the superior medullary velum. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors.

PubMed

Fukuda, Takahiro; Akiyama, Nobutake; Ikegami, Masahiro; Takahashi, Hitoshi; Sasaki, Atsushi; Oka, Hidehiro; Komori, Takashi; Tanaka, Yuko; Nakazato, Youichi; Akimoto, Jiro; Tanaka, Masahiko; Okada, Yoshikazu; Saito, Saburo

2010-05-01

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.

Melatonin, the Pineal Gland, and Circadian Rhythms

DTIC Science & Technology

1993-05-31

generating system . Brain Ra Bull. 10: 647-652, 1983. 29. Kostis, J. B., A. E. Moreyra, M. T. Amendo, J. Di Pietro, N. Cosgrove, and P. T. Kuo. The effect of...synthesis and secretion of the pineal hormone melatonin, which relies on a multisynaptic pathway via the sympathetic nervous system to maintain and...activity and other processes. However, the nature and system -level significance of this feedback are unknown. Recently published work indicates that

The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): Structure, chromosomal localization, and tissue expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coon, S.L.; Bernard, M.; Roseboom, P.H.

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, HGMW-approved symbol AANAT;EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. We have found that the human AA-NAT gene spans {approx}2.5 kb, contains four exons, and is located at chromosome 17q25. The open reading frame encodes a 23.2-kDa protein that is {approx}80% identical to sheep and rat AA-NAT. The AA-NAT transcript ({approx}1 kb) is highly abundant in the pineal gland and is expressed at lower levels in the retina and in the Y79 retinoblastoma cell line. AA-NAT mRNA is also detectable atmore » low levels in several brain regions and the pituitary gland, but not in several peripheral tissues examined. Brain and pituitary AA-NAT could modulate serotonin-dependent aspects of human behavior and pituitary function. 31 refs., 5 figs.« less

Evaluation of vector-primed cDNA library production from microgram quantities of total RNA.

PubMed

Kuo, Jonathan; Inman, Jason; Brownstein, Michael; Usdin, Ted B

2004-12-15

cDNA sequences are important for defining the coding region of genes, and full-length cDNA clones have proven to be useful for investigation of the function of gene products. We produced cDNA libraries containing 3.5-5 x 10(5) primary transformants, starting with 5 mug of total RNA prepared from mouse pituitary, adrenal, thymus, and pineal tissue, using a vector-primed cDNA synthesis method. Of approximately 1000 clones sequenced, approximately 20% contained the full open reading frames (ORFs) of known transcripts, based on the presence of the initiating methionine residue codon. The libraries were complex, with 94, 91, 83 and 55% of the clones from the thymus, adrenal, pineal and pituitary libraries, respectively, represented only once. Twenty-five full-length clones, not yet represented in the Mammalian Gene Collection, were identified. Thus, we have produced useful cDNA libraries for the isolation of full-length cDNA clones that are not yet available in the public domain, and demonstrated the utility of a simple method for making high-quality libraries from small amounts of starting material.

Pineal region tumors: results of radiation therapy and indications for elective spinal irradiation. [/sup 60/Co; x ray

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffin, B.R.; Griffin, T.W.; Tong, D.Y.K.

Eighteen patients with pineal region tumors seen from November 1960 to November 1978 were reviewed. Thirteen patients treated with radiation therapy received tumor doses in the 4000 to 5500 rad range. The five year survival and five year disease-free survival were 73 and 63% respectively. Spinal cord metastasis occurred in 2 of 13 (15%) patients. Attempts at salvage radiotherapy for these patients were unsuccessful. Computerized tomography (CT) scan provides an excellent method of evaluating the response of pineal region tumors to radiation. Rapid regression of the tumor mass on CT scan reflects the highly radioresponsive nature of germinomas, the tumormore » type most likely to disseminate throughout the neuraxis. This principle can be exploited to select unbiopsied patients with a high risk of spinal cord metastasis for prophylactic spinal radiation at an early stage of treatment.« less

Transcortical approach to a huge pineal mature teratoma.

PubMed

Berhouma, Moncef; Jemel, Hafedh; Ksira, Iadh; Khaldi, Moncef

2008-01-01

Intracranial teratomas are rare germ cell neoplasms occurring more often during childhood. We report the case of a huge mature teratoma of the pineal region in a 10-year-old patient that was not correctly diagnosed preoperatively by stereotactic biopsy. The tumor was revealed by intracranial hypertension and a Parinaud syndrome. The tumor markers were within normal levels in the serum. A left transcortical parietal approach was used to completely resect the tumor. No adjuvant treatment was given. A complete neurological recovery was observed after the surgical procedure. Follow-up at 2 years did not show any recurrence. Pineal mature teratomas have a good prognosis, in contrast to their immature or mixed counterparts. A rigorous histological examination of the tumor samples is mandatory, in order to not omit a mixed contingent within the tumor. The treatment is exclusively surgical. (c) 2008 S. Karger AG, Basel.

Significant anti-tumor effect of bevacizumab in treatment of pineal gland glioblastoma multiforme.

PubMed

Mansour, Joshua; Fields, Braxton; Macomson, Samuel; Rixe, Olivier

2014-12-01

Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas. Current standard treatment for GBM involves a combination of cytoreduction through surgical resection, followed by radiation with concomitant and adjuvant chemotherapy (temozolomide). The role of bevacizumab in the treatment of GBM continues to be a topic of ongoing research and debate. Despite aggressive treatment, these tumors remain undoubtedly fatal, especially in the elderly. Furthermore, tumors present in the pineal gland are extremely rare, accounting for only 0.1-0.4 % of all adult brain tumors, with this location adding to the complexity of treatment. We present a case of GBM, at the rare location of pineal gland, in an elderly patient who was refractory to initial standard of care treatment with radiation and concomitant and adjuvant temozolomide, but who developed a significant response to anti-angiogenic therapy using bevacizumab.

[Effect of pineal peptide on parameters of the biological age and life span in mice].

PubMed

Anisimov, V N; Khavinson, V Kh; Zavarzina, N Iu; Zabezhinskiĭ, M A; Zimina, O A; Popovich, I G; Shtylik, A V; Arutiunian, A V; Oparina, T I; Prokopenko, V M

2001-01-01

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

A Seasonal and Age-Related Study of Interstitial Cells in the Pineal Gland of Male Viscacha (Lagostomus maximus maximus).

PubMed

Busolini, Fabricio Ivan; Rosales, Gabriela Judith; Filippa, Verónica Palmira; Mohamed, Fabian Heber

2017-10-01

The pineal gland of viscacha exhibits histophysiological variations throughout the year, with periods of maximal activity in winter and minimal activity in summer. The aim of this work is to analyze the interstitial cells (IC) in the pineal gland of male viscachas in relation to season and age. The S-100 protein, glio-fibrillary acidic protein (GFAP), and vimentin were detected in adult and immature animals by immunohistochemistry (IHC). Double-IHC was also performed. The S-100 protein was localized within both, IC nucleus and cytoplasm. GFAP was present only in the cytoplasm. Vimentin was expressed in some IC, besides endothelial cells, and perivascular spaces. In the adult males, the morphometric parameters analyzed for the S-100 protein and GFAP exhibited seasonal variations with higher values of immunopositive area percentage in winter and lower values in summer, whereas the immature ones showed the lowest values for all the adult animals studied. Colocalization of S-100 protein and GFAP was observed. The IC exhibited differential expression for the proteins studied, supporting the hypothesis of the neuroectodermal origin. The IC generate an intraglandular communication network, suggesting its participation in the glandular activity regulation processes. The results of double-IHC might indicate the presence of IC in different functional stages, probably related to the needs of the cellular microenvironment. The morphometric variations in the proteins analyzed between immature and adult viscachas probed to be more salient in the latter, suggesting a direct relationship between the expression of the S-100 protein and GFAP, and animal age. Anat Rec, 2017. © 2017 Wiley Periodicals Inc. Anat Rec, 300:1847-1857, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Expression and regulation of Icer mRNA in the Syrian hamster pineal gland.

PubMed

Diaz, Elena; Garidou, Marie-Laure; Dardente, Hugues; Salingre, Anthony; Pévet, Paul; Simonneaux, Valérie

2003-04-10

Inducible-cAMP early repressor (ICER) is a potent inhibitor of CRE (cAMP-related element)-driven gene transcription. In the rat pineal gland, it has been proposed to be part of the mechanisms involved in the shutting down of the transcription of the gene coding for arylalkylamine N-acetyltransferase (AA-NAT, the melatonin rhythm-generating enzyme). In this study, we report that ICER is expressed in the pineal gland of the photoperiodic rodent Syrian hamster although with some difference compared to the rat. In the Syrian hamster pineal, Icer mRNA levels, low at daytime, displayed a 20-fold increase during the night. Nighttime administration of a beta-adrenergic antagonist, propranolol, significantly reduced Icer mRNA levels although daytime administration of a beta-adrenergic agonist, isoproterenol, was unable to raise the low amount of Icer mRNA. These observations indicate that Icer mRNA expression is induced by the clock-driven norepinephrine release and further suggest that this stimulation is restricted to nighttime, as already observed for Aa-nat gene transcription. Furthermore, we found that the daily profile of Icer mRNA displayed photoperiodic variation with a lengthening of the nocturnal peak in short versus long photoperiod. These data indicate that ICER may be involved in both daily and seasonal regulation of melatonin synthesis in the Syrian hamster.

Immune-Pineal Axis: Nuclear Factor κB (NF-κB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

PubMed Central

Markus, Regina P; Cecon, Erika; Pires-Lapa, Marco Antonio

2013-01-01

Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies. PMID:23708099

Pineal tumors: analysis of treatment results in 20 patients.

PubMed

Amendola, Beatriz E; Wolf, Aizik; Coy, Sammie R; Amendola, Marco A; Eber, Daryl

2005-01-01

The authors evaluate their results when using gamma knife surgery (GKS) in the management of patients with tumors in the pineal region. This is a retrospective clinical evaluation of 20 patients with primary tumors of the pineal region treated with GKS from November 1994 through August 2003. There were 13 germ cell tumors, two pineoblastomas, two low-grade gliomas, one primitive neuroectodermal tumor, one teratoma, and one pineocytoma. There were 10 male and 10 female patients. Their median age was 15.5 years (range 5-71 years). The median margin dose was 11 Gy (range 8-20 Gy). The median target volume was 3.1 cm3 (range 0.1-49.9 cm3). Five patients received sequential systemic chemotherapy and four underwent adjuvant conventional radiation therapy. Seventeen (85%) of 20 patients are alive with a median survival of 30.4 months (range 0-85.7 months). Two patients required retreatment. Three patients died: one of unrelated causes, one who presented with extensive local disease, and the other of meningeal carcinomatosis with local control of the primary tumor. No complications from GKS were noted. This initial experience suggests that GKS is a valuable treatment modality for the management of pineal region tumors. This technique offers excellent local tumor control and minimal patient morbidity, allowing for immediate use of systemic chemotherapy and/or conventional radiation if indicated.

New Sensitive Serum Melatonin Radioimmunoassay Employing the Kennaway G280 Antibody: Syrian Hamster Morning Adrenergic Response,

DTIC Science & Technology

1993-01-01

NE- induced aMT secretion into 1111 their pineals in vitro, either to the transmitter the medium was markedly diminished in pineals taken S...al., 1988; Bieck et al., 1988; Khoory and effect of exercise ) but without assessing whether the Stemme, 1988; Tortosa et al., 1989; Soudtre et al...above twice aMT surge) or injected ISO ( inducing a secondary the conservative estimate of the ALD. surge at night after acute inhibition by light) re

The pineal gland - Its possible roles in human reproduction

NASA Technical Reports Server (NTRS)

Brzezinski, Amnon; Wurtman, Richard J.

1988-01-01

The paper discusses the role of the pineal gland in controlling mammalian reproduction, with particular attention given to the role of melatonin in polyestrus mammals, like humans and laboratory rodents. Evidence is cited indicating the influence of melatonin production and blood content on the age of puberty, the timing of the ovulatory cycle, gonadal steriodogenesis, and patterns of reproductive behavior. It is suggested that abnormal patterns of melatonin might be associated with amenorrhea, anovulation, unexplained infertility, premature menopause, and habitual abortions.

[MRI of the pineal gland].

PubMed

Langevad, Line; Madsen, Camilla Gøbel; Siebner, Hartwig; Garde, Ellen

2014-11-10

The pineal gland (CP) is located centrally in the brain and produces melatonin. Cysts and concrements are frequent findings on MRI but their significance is still unclear. The visualization of CP is difficult due to its location and surrounding structures and so far, no standardized method exists. New studies suggest a correlation between CP-morphology and melatonin secretion as well as a connection between melatonin, disturbed circadian rhythm, and the development of cancer and cardiovascular diseases, underlining the need for a standardized approach to CP on MRI.

Radiometric assay for phenylethanolamine N-methyltransferase and catechol O-methyltransferase in a single tissue sample: application to rat hypothalamic nuclei, pineal gland, and heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Culman, J.; Torda, T.; Weise, V.K.

A simple and highly sensitive method for simultaneous assay of phenylethanolamine N-methyltransferase (PNMT) and catechol O-methyltransferase (COMT) is described. These enzymes are determined in a single tissue homogenate using S-(methyl-/sup 3/H) adenosyl-L-methionine as methyl donor and sequentially incubating with the substrates phenylethanolamine and epinephrine. The radioactive products of the enzymatic reactions, N-methylphenylethanolamine and metanephrine, are extracted and then separated by thin-layer chromatography. The identity of the reaction products has been established chromatographically and the conditions for both enzymatic reactions in the assay procedure have been defined. Measurement of PNMT activity in the rat pineal gland or in minute fragments ofmore » other tissues (e.g., brain nuclei) has not been possible using previously described methods. Activities of PNMT and COMT in the rat pineal gland, various hypothalamic nuclei, and the auricular and ventricular myocardia are herein reported.« less

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

PubMed Central

Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure. PMID:29713348

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach.

PubMed

Dobran, Mauro; Nasi, Davide; Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

Praying Sitting Position for Pineal Region Surgery: An Efficient Variant of a Classic Position in Neurosurgery.

PubMed

Choque-Velasquez, Joham; Colasanti, Roberto; Resendiz-Nieves, Julio C; Gonzáles-Echevarría, Kléber E; Raj, Rahul; Jahromi, Behnam Rezai; Goehre, Felix; Lindroos, Ann-Christine; Hernesniemi, Juha

2018-05-01

The sitting position has lost favor among neurosurgeons partly owing to assumptions of increased complications, such as venous air embolisms and hemodynamic disturbances. Moreover, the surgeon must assume a tiring posture. We describe our protocol for the "praying position" for pineal region surgery; this variant may reduce some of the risks of the sitting position, while providing a more ergonomic surgical position. A retrospective review of 56 pineal lesions operated on using the praying position between January 2008 and October 2015 was performed. The praying position is a steeper sitting position with the upper torso and the head bent forward and downward. The patient's head is tilted about 30° making the tentorium almost horizontal, thus providing a good viewing angle. G-suit trousers or elastic bandages around the lower extremities are always used. Complete lesion removal was achieved in 52 cases; subtotal removal was achieved in 4. Venous air embolism associated with persistent hemodynamic changes was nonexistent in this series. When venous air embolism was suspected, an immediate reaction based on good teamwork was imperative. No cervical spine cord injury or peripheral nerve damage was reported. The microsurgical time was <45 minutes in most of the cases. Postoperative pneumocephalus was detected in all patients, but no case required surgical treatment. A protocolized praying position that includes proper teamwork management may provide a simple, fast, and safe approach for proper placement of the patient for pineal region surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Isolation and characterization of melanopsin and pinopsin expression within photoreceptive sites of reptiles

NASA Astrophysics Data System (ADS)

Frigato, Elena; Vallone, Daniela; Bertolucci, Cristiano; Foulkes, Nicholas S.

2006-08-01

Non-mammalian vertebrates have multiple extraocular photoreceptors, mainly localised in the pineal complex and the brain, to mediate irradiance detection. In this study, we report the full-length cDNA cloning of ruin lizard melanopsin and pinopsin. The high level of identity with opsins in both the transmembrane regions, where the chromophore binding site is located, and the intracellular loops, where the G-proteins interact, suggests that both melanopsin and pinopsin should be able to generate a stable photopigment, capable of triggering a transduction cascade mediated by G-proteins. Phylogenetic analysis showed that both opsins are located on the expected branches of the corresponding sequences of ortholog proteins. Subsequently, using RT-PCR and RPA analysis, we verified the expression of ruin lizard melanopsin and pinopsin in directly photosensitive organs, such as the lateral eye, brain, pineal gland and parietal eye. Melanopsin expression was detected in the lateral eye and all major regions of the brain. However, different from the situation in Xenopus and chicken, melanopsin is not expressed in the ruin lizard pineal. Pinopsin mRNA expression was only detected in the pineal complex. As a result of their phylogenetic position and ecology, reptiles provide the circadian field with some of the most interesting models for understanding the evolution of the vertebrate circadian timing system and its response to light. This characterization of melanopsin and pinopsin expression in the ruin lizard will be important for future studies aimed at understanding the molecular basis of circadian light detection in reptiles.

Results of surgery in symptomatic non-hydrocephalic pineal cysts: role of magnetic resonance imaging biomarkers indicative of central venous hypertension.

PubMed

Eide, Per Kristian; Ringstad, Geir

2017-02-01

We have previously proposed that pineal cysts (PCs) may result in crowding of the pineal recess, causing symptoms due to compression of the internal cerebral veins and central venous hypertension. In the present study, we compared clinical outcome of different treatment modalities in symptomatic individuals with non-hydrocephalic PCs. The study included all patients managed surgically for non-hydrocephalic PCs in our Department of Neurosurgery over a 10-year period. We applied a questionnaire to determine occurrence of symptoms before and after surgery, which allowed the use of a grading scale for symptom severity. Magnetic resonance imaging (MRI) biomarkers indicative of central venous hypertension were assessed before and after surgery. Relief of symptoms after surgery was most efficiently obtained by complete microsurgical cyst removal [n = 15; no (0/15), some (1/15) or marked (14/15) improvement], and to a lesser extent by microsurgical cyst fenestration [n = 6; no (2/6), some (4/6) or marked (0/6) improvement]. Shunt surgery was not successful [n = 6; no (5/6), some (1/6) or marked (0/6) improvement]. In all patients, the proposed MRI biomarkers gave evidence of central venous hypertension (PC grades 2-4). Microsurgical cyst removal provided marked symptom relief in symptomatic individuals with non-hydrocephalic PCs and MRI biomarkers of central venous hypertension. The hypothesis that PC-induced crowding of the pineal recess may compromise venous run-off and induce a central venous hypertension syndrome deserves further study.

Melatonin concentrations in the sudden infant death syndrome

NASA Technical Reports Server (NTRS)

Sturner, W. Q.; Lynch, H. J.; Deng, M. H.; Gleason, R. E.; Wurtman, R. J.

1990-01-01

The melatonin levels in various body fluids of the sudden infant death syndrome (SIDS) infants are compared with those of infants of comparable age who died of other causes to examine a possible relationship between pineal function and SIDS. After adjusting for age differences, cerebrospinal fluid melatonin levels are found to be significantly lower in the SIDS infants. It is suggested that diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

Electric and magnetic fields and tumor progression. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keng, P.C.; Grota, L.J.; Michaelson, S.

This laboratory study has rigorously investigated two previously reported biological effects of 60-Hz electric and magnetic fields. The first effect involves nighttime suppression of melatonin synthesis in the pineal glands of rats exposed to high electric fields. The second concerns the increase in colony forming ability of human colon cancer cells exposed to 1.4-G magnetic fields. Neither effect was detected in the present study. A series of published laboratory studies on rats reported that 60-Hz electric fields at various field levels up to 130 kV/m suppress the nighttime synthesis of melatonin, a hormone produced by the pineal gland. Since melatoninmore » is known to modulate the immune system and may inhibit cancer cell activity, changes in physiological levels of melatonin may have significant health consequences. In the repeat experiments, field exposure did not alter nighttime levels of melatonin or enzyme activities in the pineal gland. A small but statistically significant reduction of about 20% in serum melatonin was seen in exposed animals. Pineal melatonin was also unaffected by the presence of red light as a cofactor with field exposure or by time-shifting the daily field exposure period. Another study reported that 60-Hz magnetic fields can affect the colony forming ability of human cancer cells after exposure in a culture medium. In the repeat experiments, field exposure did not alter the colony forming ability of human Colo 205 cells in two different cell concentrations at plating or in two different incubation conditions. Field exposure also did not affect cell cycling in any of the four cell lines tested.« less

Influence of photoperiod on pineal melatonin synthesis, fur color, body weight, and reproductive function in the female Djungarian hamster, Phodopus sungorus.

PubMed

Lerchl, A; Schlatt, S

1993-01-01

In order to investigate female Djungarian hamsters' reactions to changes of the photoperiod, the following two experiments were performed. Experiment I: Age-matched female hamsters were exposed to either short (8L:16D) or long days (16L:8D) for 38 weeks. Initially, the short-day group showed a decline in body weight, associated with changes in gonadal function and fur color. This was not maintained by the short-day group which returned, on the most part, to long-day levels, thus becoming insensitive to this regressive lighting regimen. The time courses of these events compare well with those observed in males, which suggests a common mechanism. Experiment II: Two groups of female hamsters were exposed for 8 weeks to either long days or short days. At the end of the test period, the diurnal variations in pineal content of melatonin, serotonin, hydroxyindole acetic acid, and serum melatonin were estimated, revealing marked differences between the two groups. Not only was there a prolongation of melatonin synthesis observed in the short-day animals, but there was also a significant elevation of the melatonin levels when compared to the long-day animals. Together with recent findings in males, these findings lend support to the hypothesis that, in the Djungarian hamster, the elevation of nocturnal melatonin levels may be of additional significance, with respect to the physiological changes induced by short-day photoperiods.

Afternoon serum-melatonin in sleep disordered breathing.

PubMed

Ulfberg, J; Micic, S; Strøm, J

1998-08-01

To study afternoon serum-melatonin values in patients with sleep disordered breathing. Melatonin has a strong circadian rhythm with high values during the night-time and low values in the afternoon. Sleep disordered breathing may change the circadian rhythm of melatonin which may have diagnostic implications. The Sleep Laboratory, The Department of Internal Medicine, Avesta Hospital, Sweden, and the Department of Anaesthesiology, Glostrup University Hospital, Copenhagen, Denmark. We examined 60 consecutive patients admitted for sleep disordered breathing and 10 healthy non snoring controls. The patients underwent a sleep apnoea screening test having a specificity of 100% for the obstructive sleep apnoea syndrome (OSAS) using a combination of static charge sensitive bed and oximetry. Obstructive sleep apnoea syndrome was found in 49 patients, eight patients had borderline sleep disordered breathing (BSDB) and three patients were excluded due to interfering disease. Patients and controls had an afternoon determination of serum-melatonin. The Epworth Sleepiness Scale was used to score day-time sleepiness. In comparison with normal controls patients suffering from OSAS had significantly higher serum-melatonin levels in the afternoon. However, as a diagnostic test for OSAS in patients with sleep disordered breathing serum-melatonin showed a low sensitivity but a high specificity. The results indicate that breathing disorders during sleep in general affect pineal function. Sleep disordered breathing seems to disturb pineal function. Determination of afternoon serum-melatonin alone or together with a scoring of daytime sleepiness does not identify OSAS-patients in a heterogeneous population of patients complaining of heavy snoring and excessive daytime sleepiness.

A neurologist looks at mind and brain: "the enchanted loom".

PubMed

Hansotia, Phiroze

2003-10-01

For a long time, before we developed an appreciation of the neuroanatomy and neurophysiology of the brain, there was uncertainty as to the nature and source of the human mind. Philosophers linked the mind to mythical "humors" that controlled the human body, and others speculated that the mind was associated with "life-force" or soul. Few felt that there was a relation between the human mind and brain, but they had to wait for the Age of Enlightenment and scientific discovery in the 18th and 19th centuries to establish a clear association between the two. Three centuries ago Rene Descartes described the mind as an extracorporeal entity that was expressed through the pineal gland. Descartes was wrong about the pineal, but the debate he set off regarding the relationship between mind and brain rages on. This review looks at the history of speculation on the mind and the development of ideas that have led to our present understanding of this phenomenon. The basic anatomy and physiology of the brain is reviewed to help us understand the brain's association with the complex function we call mind. This is followed by a look at some syndromes that may result when part of the brain is damaged-the parietal lobe is arbitrarily selected as an example-and the resulting effect on the subject's mind. This assists us in understanding the association of mind and brain, and also to better understanding its components, behavior, function and dysfunction.

Pineal and ectopic pineal tumors: the role of radiation therapy. [X ray; /sup 60/Co

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, Y.T.R.; Medini, E.; Haselow, R.E.

Seventeen patients with pineal tumors and one ectopic (suprasellar) germinoma were treated with radiation therapy. Surgery was restricted to decompression in 16 patients, and only two patients had resection of the tumor. Thirteen of 18 patients are alive without evidence for disease with a ten-year surrvival rate of 88%. The tumor dose ranged from 4000 rads to 6000 rads. No age or dose dependence in survival was noted, but patients with whole brain irradiation or generous volume to include ventricular system had better survival. No case of spinal metastasis was noted. The possibility of increased incidence of meningeal seeding followingmore » surgical intervention is considered. From their data, the authors feel that radiation therapy with or without surgical decompression should be the primary treatment for pinealoma. Surgery can be used for diagnosis and/or treatment of patients who show delayed response to radiation. Recommendation is made for the use of whole brain irradiation to 4000 rads followed by a boost to the tumor area to 5000 rads.« less

Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy☆

PubMed Central

Sun, Bin; Feng, Xing; Ding, Xin; Bao, Li; Li, Yongfu; He, Jun; Jin, Meifang

2012-01-01

Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the clock genes Clock and Bmal1, in the pineal gland of rats with hypoxic-ischemic brain damage. Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia. Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours. The levels of Bmal1 mRNA reached a peak at 36 hours, but were significantly reduced at 48 hours. Experimental findings indicate that Clock and Bmal1 genes were indeed expressed in the pineal glands of neonatal rats. At the initial stage (within 36 hours) of hypoxic-ischemic brain damage, only slight changes in the expression levels of these two genes were detected, followed by significant changes at 36–48 hours. These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage. PMID:25538743

Health Related Aspects of Artificial Light

NASA Astrophysics Data System (ADS)

Hansler, Richard; Kubulins, Vilnis; Carome, Edward

2011-04-01

It was long thought that the "sleep hormone," melatonin, is produced by the pineal gland only when the eyes are in darkness. Thus, in developed countries, due to the use of electric lighting after dark, melatonin production usually occurs only when one is asleep. For most people, this is substantially less than the 9 to 10 hour production time capability of the pineal gland. However, in 2001 it was discovered that not all light, but mainly a band of wavelengths in the blue portion of the spectrum, below 530nm, suppresses melatonin production. On learning this, and that melatonin is a very active cancer fighting antioxidant and has many other health promoting properties, it was decided to make available lighting products that can enhance melatonin production. Included are lamps that do not emit the offending blue wavelengths and eyeglasses that filter out the blue portion of the spectrum. These and other related products are meant to be used for several hours in the evening, before retiring, thus maximizing the pineal gland's production time. The effects of their use on sleep and several other health related conditions are discussed.

Pineal region tumors: analysis of treatment results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amendola, B.E.; McClatchey, K.; Amendola, M.A.

This article represents a review of 32 patients with pineal region tumors seen and treated at the University of Michigan Medical Center from January 1950 to December 1980. All patients presented with manifestations of increased intracranial pressure: limitation of the upward gaze (Parinaud's syndrome), hydrocephalus and a mass in the posterior aspect of the third ventricle. The tumor was demonstrated by pneumoencephalography, ventriculography, angiography or CT scans. Ventricular decompression was performed in all patients. Twenty-seven patients received post-operative irradiation. The overall 10 year survival for evaluable patients was 16/24 (67%). Few complications were seen.

[The influence of substances revealing geroprotective of spontaneous carcinogenesis in mice].

PubMed

Popovich, I G

2004-01-01

The review presents the results of experimental studies conducted by the author. CBA, SHR, HER-2/neu and SAM mice revealed inhibition of age-related alterations in estrus function and spontaneous tumour development and showed life span extension under the influence of the pineal gland hormone Melatonin, synthetic peptide bioregulator Epitalon, delta-sleep-inducing peptide Deltaran, enterosorbent Aqualen and succinic acid containing preparation Neuronol (Noogam). The observed effect depended on the dose and conditions of administration, as well as genetic predisposition of the particular mice strains to tumour development.

Postnatal neurogenesis in the cow pineal gland: an immunohistochemical study.

PubMed

Gómez Esteban, M B; Muñoz Mosqueira, M I; Arroyo, A A; Muñoz Barragán, L

2013-03-01

In the pineal gland of cows and rats structures designated rosettes have been described both during embryonic development and in adult animals. In order to investigate the possible nature of the cells comprising such structures, in the present work we studied the pineal glands from 10 cows of one- or four-years-old using conventional immunocytochemical and confocal microscopy techniques. As markers of glial cells, we used anti-vimentin (Vim) and glial fibrillary acidic protein (GFAP) and anti-S-100 sera, and the pinealocytes were labelled with β-III tubulin. As a marker of stem cells, we used an antinestin serum, while an anti-PCNA serum was employed to label proliferating cells. To explore the neuronal nature of some cells of the rosettes, we used an anti-SRIF serum. The rosettes were seen to be present throughout the glandular parenchyma and displayed a central cavity surrounded by cells, most of which expressed all or just some of the above glial labels and nestin, although there were also some rosettes with cells that expressed β-III tubulin and other cells that expressed SRIF. Likewise, in the cells of the rosettes the cell nucleus showed strong expression of PCNA. Confocal microscopy revealed that the walls of the rosettes contained cells that coexpressed Vim/S-100, Vim/GFAP and Vim/nestin. The number of rosettes was significantly greater in the animals of one year of age with respect to the four-year-old cows. The present findings allow us to suggest that rosettes are evolving structures and that most of the cells present in their walls should be considered stem cells, and hence responsible for the postnatal neurogenesis occurring in the pineal gland of cows.

Rhythmic Diurnal Synthesis and Signaling of Retinoic Acid in the Rat Pineal Gland and Its Action to Rapidly Downregulate ERK Phosphorylation.

PubMed

Ashton, Anna; Stoney, Patrick N; Ransom, Jemma; McCaffery, Peter

2018-03-08

Vitamin A is important for the circadian timing system; deficiency disrupts daily rhythms in activity and clock gene expression, and reduces the nocturnal peak in melatonin in the pineal gland. However, it is currently unknown how these effects are mediated. Vitamin A primarily acts via the active metabolite, retinoic acid (RA), a transcriptional regulator with emerging non-genomic activities. We investigated whether RA is subject to diurnal variation in synthesis and signaling in the rat pineal gland. Its involvement in two key molecular rhythms in this gland was also examined: kinase activation and induction of Aanat, which encodes the rhythm-generating melatonin synthetic enzyme. We found diurnal changes in expression of several genes required for RA signaling, including a RA receptor and synthetic enzymes. The RA-responsive gene Cyp26a1 was found to change between day and night, suggesting diurnal changes in RA activity. This corresponded to changes in RA synthesis, suggesting rhythmic production of RA. Long-term RA treatment in vitro upregulated Aanat transcription, while short-term treatment had no effect. RA was also found to rapidly downregulate extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, suggesting a rapid non-genomic action which may be involved in driving the molecular rhythm in ERK1/2 activation in this gland. These results demonstrate that there are diurnal changes in RA synthesis and activity in the rat pineal gland which are partially under circadian control. These may be key to the effects of vitamin A on circadian rhythms, therefore providing insight into the molecular link between this nutrient and the circadian system.

Gliosarcomas arising from the pineal gland region: uncommon localization and rare tumors.

PubMed

Sugita, Yasuo; Terasaki, Mizuhiko; Tanigawa, Ken; Ohshima, Koichi; Morioka, Motohiro; Higaki, Koichi; Nakagawa, Setsuko; Shimokawa, Shoko; Nakashima, Susumu

2016-02-01

Gliosarcomas are a variant of glioblastomas and present a biphasic pattern, with coexisting glial and mesenchymal components. In this study, two unusual cases are presented. Case 1 is a 52-year-old woman with a headache and memory disturbance for a month. Case 2 is an 18-year-old man with a headache lasting two weeks. In both cases, an MRI revealed enhancing T1-low to iso, T2-iso to high intensity lesions in the pineal gland region. Histologically, in case 1, the tumor showed spindle cell proliferation with disorganized fascicles and cellular pleomorphism. Tumor cells variously exhibited oncocytic transformation. Immunohistochemically, most of the spindle tumor cells were positive for myoglobin and desmin. Some of the tumor cells were positive for GFAP and S-100 protein. On the other hand, all tumor cells were positive for CD133, Musashi1, and SOX-2 which are the markers of neural stem cells. In case 2, the tumor showed monotonous proliferation of short spindle cells with disorganized fascicles and cellular atypism. The morphological distinction between glial and mesenchymal components was not apparent. Immunohistochemically, most of the spindle tumor cells were positive for desmin. Glial tumor cells that were dispersed within the sarcoma as single cells were positive for GFAP. In addition, all tumor cells were positive for CD133, Musashi1 and SOX-2. Based on these microscopic appearances, and immunohistochemical findings, these cases were diagnosed as gliosarcomas arising from the pineal gland region. These results also indicated that pluripotential cancer stem cells differentiated into glial and muscle cell lines at the time of tumor growth. In a survey of previous publications on gliosarcoma arising from the pineal gland, these cases are the second and third reports found in English scientific writings. © 2015 Japanese Society of Neuropathology.

Moonlight affects nocturnal Period2 transcript levels in the pineal gland of the reef fish Siganus guttatus.

PubMed

Sugama, Nozomi; Park, Ji-Gweon; Park, Yong-Ju; Takeuchi, Yuki; Kim, Se-Jae; Takemura, Akihiro

2008-09-01

The golden rabbitfish Siganus guttatus is a reef fish with a restricted lunar-synchronized spawning cycle. It is not known how the fish recognizes cues from the moon and exerts moon-related activities. In order to evaluate the perception and utilization of moonlight by the fish, the present study aimed to clone and characterize Period2 (Per2), a light-inducible clock gene in lower vertebrates, and to examine daily variations in rabbitfish Per2 (rfPer2) expression as well as the effect of light and moonlight on its expression in the pineal gland. The partially-cloned rfPer2 cDNA (2933 bp) was highly homologous (72%) to zebrafish Per2. The rfPer2 levels increased at ZT6 and decreased at ZT18 in the whole brain and several peripheral organs. The rfPer2 expression in the pineal gland exhibited a daily variation with an increase during daytime. Exposing the fish to light during nighttime resulted in a rapid increase of its expression in the pineal gland, while the level was decreased by intercepting light during daytime. Two hours after exposing the fish to moonlight at the full moon period, the rfPer2 expression was upregulated. These results suggest that rfPer2 is a light-inducible clock gene and that its expression is affected not only by daylight but also by moonlight. Since the rfPer2 expression level during the full moon period was higher than that during the new moon period, the monthly variation in the rfPer2 expression is likely to occur with the change in amplitude between the full and new moon periods.

Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

PubMed

Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

2015-01-01

The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

What do we (need to) know about the melatonin in crustaceans?

PubMed

Sainath, S B; Swetha, Ch; Reddy, P Sreenivasula

2013-08-01

Melatonin (N-acetyl-5-methoxy-tryptamine) was first discovered from the bovine pineal gland extract in 1958. Since then, its synthesis, metabolism, physiological, and patho-physiological functions are well studied in vertebrates; there is an increasing recognition of melatonin in invertebrates and especially in crustaceans. The presence of melatonin in crustaceans is now well documented and some functional aspects in the framework of crustacean biology have been demonstrated. This review aims at giving a comprehensive overview of the various physiological events regulated by this pleiotropic hormone. Topics include: glucose homeostasis, regulation of reproduction, molting, limb regeneration, and antioxidant properties. Finally, perspectives on current and possible research are offered. Copyright © 2013 Wiley Periodicals, Inc.

Characteristics of the norepinephrine-stimulated phosphatidylinositol turnover in rat pineal cell dispersions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hauser, G.; Smith, T.L.

Dispersed rat pineal cells can be used for the study of the phosphatidylinositol effect. The response to ( - )-norepinephrine of the incorporation of 32Pi into phospholipids is linear with time and cell concentration, stereospecific, and mediated through alpha-1-adrenergic receptors. Na+ in the incubation medium is obligatory for labeling of phosphatidylinositol and phosphatidylcholine by 32P. In the absence of K+, incorporation of 32P is drastically lowered and no stimulation by norepinephrine occurs. Rb+ can replace K+. Omission of Ca2+ or substitution with Sr2+ preferentially lowers incorporation of radioactivity into phosphatidylcholine. Mg2+ is not required for basal or stimulated labeling.

[The effect of pineal peptide preparations on proliferative activity in organotypic culture of the preoptic hypothalamus area].

PubMed

Miliutina, Iu P; Kozina, L S; Arutiunian, A V; Chalisova, N I; Lesniak, V V; Morozova, P Iu

2007-01-01

In investigations carried out with organotypic culture of mediobasal preoptic area (MPA) of hypothalamus it was established that pineal peptide preparations epitalon (2 ng/ml) and epithalamin (100 ng/ml) stimulate the development of proliferative activity of explants in 3 month and 24 months female rats. It has been shown that epithalamin is more effective in young rats in comparison with old animals, but epitalon as well as epithalamin have almost the same less pronounced inducing effect on growth zone in MPA explants from young and old animals. This effect is tissue specific and could be dependent on inhibition of apoptosis.

Descartes and His Peculiar Sleep Pattern.

PubMed

Damjanovic, Aleksandar; Milovanovic, Srdjan D; Trajanovic, Nikola N

2015-01-01

Rene Descartes (1596-1650) was a mathematician, philosopher, and scholar, whose work set a foundation for modern science. Among other interests, he focused on locating the "core and the seat of the soul" and concluded that the pineal gland was such a structure. Recent scientific findings validate Descartes' deep interest in pineal gland, appreciating its role as part of the circadian rhythm system. On the other hand, the biographical information suggests that Descartes had an aberration of the circadian rhythm (delayed sleep phase). Coincidentally, this meant that one of the most important things in his private life and one of the most significant areas of his research intersected in an overlooked way.

Masking of central diabetes insipidus and hypogonadotrophic hypogonadism by germ cell tumour in suprasellar--pineal region.

PubMed

Isa, S H Md; Wong, M; Khalid, B A K

2006-12-01

A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism.

LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.

PubMed

Barker, Steven A; Borjigin, Jimo; Lomnicka, Izabela; Strassman, Rick

2013-12-01

We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat. Copyright © 2013 John Wiley & Sons, Ltd.

[The pineal gland's peptides factors and the rhythms of functions of the thymus and bone marrow in animals during aging].

PubMed

Labunets, I F; Butenko, G M; Dragunova, V A; Magdich, L V; Kopylova, G V; Rodnichenko, A E; Mikhal'skiĭ, S A; Khavinson, V Kh; Azarskova, M V; Maksiuk, T V

2004-01-01

It was investigated the influence of pineal peptides on the aging changes both circadian rhythm of thymic serum factor (FTS) titer in male rats Wistar and circannual rhythms of FTS, the amount of stromal cells-precurcors (CFC-F), granulocyte-macrophage cells-precurcors (CFC-GM), CD4+, Mac-1+ and CD19+-cells in bone marrow of male mice CBA. Epithalamin was injected chronically beginning from 6 month in rats and 4 month in mice. In old animals the rhythmical disturbancers of the indices characterized by loss of fluctuations, displacement of seasonal acrophase, increased or diminished amplitude, inversion of rhythm and desynchronization. After epithalamin injections in rats of 11, 17, 27 months the FTS titer at night increased and in old mice of 23-24 months appeared the peak of hormone level in summer-autumn, restored the difference between the amount of CD4+, Mac-1+-cells in bone marrow in spring and autumn, increased CFC-GM amount in spring, diminished CFC-F in autumn and increased this indice in winter. Epithalon also diminished of CFC-GM and CFC-F amount in old mice in autumn. The retarding age-related disturbances of suprachiasmaticus nucleus of hypothalamus structure, the diminishing corticosterone and testosterone levels at night, the increasing hormones level in summer and the falling in winter plays role in the improvement of thymus and bone marrow rhythmical function in old animals, reseaved epithalamin. The rhythms of most indices rhythms in old animals showed a pattern of adult.

Rhythms at the bottom of the deep sea: Cyclic current flow changes and melatonin patterns in two species of demersal fish

NASA Astrophysics Data System (ADS)

Wagner, H.-J.; Kemp, K.; Mattheus, U.; Priede, I. G.

2007-11-01

We have studied physical and biological rhythms in the deep demersal habitat of the Northeastern Atlantic. Current velocity and direction changes occurred at intervals of 12.4 h, demonstrating that they could have an impact of tidal activity, and also showed indications of other seasonal changes. As an indicator of biological rhythms, we measured the content of pineal and retinal melatonin in the grenadier Coryphaenoides armatus and the deep-sea eel Synaphobranchus kaupii, and determined the spontaneous release of melatonin in long-term (52 h minimum) cultures of isolated pineal organs and retinae in S. kaupii. The results of the release experiments show statistically significant signs of synchronicity and periodicity suggesting the presence of an endogenous clock. The melatonin content data show large error bars typical of cross-sectional population studies. When the data are plotted according to a lunar cycle, taken as indication of a tidal rhythm, both species show peak values at the beginning of the lunar day and night and lower values during the second half of lunar day and night and during moonrise and moonset. Statistical analysis, however, shows that the periodicity of the melatonin content is not significant. Taken together these observations strongly suggest that (1) biological rhythms are present in demersal fish, (2) the melatonin metabolism shows signs of periodicity, and (3) tidal currents may act as zeitgeber at the bottom of the deep sea.

Limited-field radiation for bifocal germinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lafay-Cousin, Lucie; Millar, Barbara-Ann; Mabbott, Donald

Purpose: To report the incidence, characteristics, treatment, and outcomes of bifocal germinomas treated with chemotherapy followed by focal radiation. Methods and Materials: This was a retrospective review. Inclusion criteria included radiologic diagnosis of bifocal germinoma involving the pineal and neurohypophyseal region, no evidence of dissemination on spinal MRI, negative results from cerebrospinal fluid cytologic evaluation, and negative tumor markers. Results: Between 1995 and 2004, 6 patients (5 male, 1 female; median age, 12.8 years) fulfilled the inclusion criteria. All had symptoms of diabetes insipidus at presentation. On MRI, 4 patients had a pineal and suprasellar mass, and 2 had amore » pineal mass associated with abnormal neurohypophyseal enhancement. All patients received chemotherapy followed by limited-field radiation and achieved complete remission after chemotherapy. The radiation field involved the whole ventricular system (range, 2,400-4,000 cGy) with or without a boost to the primary lesions. All patients remain in complete remission at a median follow-up of 48.1 months (range, 9-73.4 months). Conclusions: This experience suggests that bifocal germinoma can be considered a locoregional rather than a metastatic disease. Chemotherapy and focal radiotherapy might be sufficient to provide excellent outcomes. Staging refinement with new diagnostic tools will likely increase the incidence of the entity.« less

Amyloid β peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway.

PubMed

Cecon, Erika; Chen, Min; Marçola, Marina; Fernandes, Pedro A C; Jockers, Ralf; Markus, Regina P

2015-06-01

Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT₁ and MT₂, but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid β peptides (Aβ(1-40) and Aβ(1-42)). Aβ treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up-regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle-treated glands. Blocking NF-κB activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT₁ or MT₂ receptors to Aβ lead to a 40% reduction in [(125)I]iodomelatonin binding to MT₁. ERK1/2 activation triggered by MTRs, but not by the β₂-adrenergic receptor, was markedly impaired by Aβ in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of Aβ, opening new perspectives to Alzheimer disease diagnosis and therapeutic intervention. © FASEB.

Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish.

PubMed

Shainer, Inbal; Buchshtab, Adi; Hawkins, Thomas A; Wilson, Stephen W; Cone, Roger D; Gothilf, Yoav

2017-03-20

The neuropeptide agouti-related protein (AgRP) is expressed in the arcuate nucleus of the mammalian hypothalamus and plays a key role in regulating food consumption and energy homeostasis. Fish express two agrp genes in the brain: agrp1, considered functionally homologous with the mammalian AgRP, and agrp2. The role of agrp2 and its relationship to agrp1 are not fully understood. Utilizing BAC transgenesis, we generated transgenic zebrafish in which agrp1- and agrp2-expressing cells can be visualized and manipulated. By characterizing these transgenic lines, we showed that agrp1-expressing neurons are located in the ventral periventricular hypothalamus (the equivalent of the mammalian arcuate nucleus), projecting throughout the hypothalamus and towards the preoptic area. The agrp2 gene was expressed in the pineal gland in a previously uncharacterized subgroup of cells. Additionally, agrp2 was expressed in a small group of neurons in the preoptic area that project directly towards the pituitary and form an interface with the pituitary vasculature, suggesting that preoptic AgRP2 neurons are hypophysiotropic. We showed that direct synaptic connection can exist between AgRP1 and AgRP2 neurons in the hypothalamus, suggesting communication and coordination between AgRP1 and AgRP2 neurons and, therefore, probably also between the processes they regulate.

Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiland, N.G.; Wise, P.M.

Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silasticmore » capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.« less

Role of monochromatic light on daily variation of clock gene expression in the pineal gland of chick.

PubMed

Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

2016-11-01

The avian pineal gland is a master clock that can receive external photic cues and translate them into output rhythms. To clarify whether a shift in light wavelength can influence the circadian expression in chick pineal gland, a total of 240 Arbor Acre male broilers were exposed to white light (WL), red light (RL), green light (GL) or blue light (BL). After 2weeks light illumination, circadian expressions of seven core clock genes in pineal gland and the level of melatonin in plasma were examined. The results showed after illumination with monochromatic light, 24h profiles of all clock gene mRNAs retained circadian oscillation, except that RL tended to disrupt the rhythm of cCry2. Compared to WL, BL advanced the acrophases of the negative elements (cCry1, cCry2, cPer2 and cPer3) by 0.1-1.5h and delayed those of positive elements (cClock, cBmal1 and cBmal2) by 0.2-0.8h. And, RL advanced all clock genes except cClock and cPer2 by 0.3-2.1h, while GL delayed all clock genes by 0.5-1.5h except cBmal2. Meanwhile, GL increased the amplitude and mesor of positive and reduced both parameters of negative clock genes, but RL showed the opposite pattern. Although the acrophase of plasma melatonin was advanced by both GL and RL, the melatonin level was significantly increased in GL and decreased in RL. This tendency was consistent with the variations in the positive clock gene mRNA levels under monochromatic light and contrasted with those of negative clock genes. Therefore, we speculate that GL may enhance positive clock genes expression, leading to melatonin synthesis, whereas RL may enhance negative genes expression, suppressing melatonin synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Endotoxin-induced inflammation disturbs melatonin secretion in ewe

PubMed Central

Herman, Andrzej Przemysław; Wojtulewicz, Karolina; Bochenek, Joanna; Krawczyńska, Agata; Antushevich, Hanna; Pawlina, Bartosz; Zielińska-Górska, Marlena; Herman, Anna; Romanowicz, Katarzyna; Tomaszewska-Zaremba, Dorota

2017-01-01

Objective The study examined the effect of intravenous administration of bacterial endotoxin—lipopolysaccharide (LPS) —on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12). Methods In both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively. Results Endotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland. Conclusion The present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod. PMID:28728370

Sunitinib in Treating Patients With Recurrent Malignant Gliomas

ClinicalTrials.gov

2016-01-29

Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

Age-dependent tissue-specific exposure of cell phone users.

PubMed

Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

2010-04-07

The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

Age-dependent tissue-specific exposure of cell phone users

NASA Astrophysics Data System (ADS)

Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

2010-04-01

The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

PubMed Central

Peschke, Elmar; Bähr, Ina; Mühlbauer, Eckhard

2013-01-01

The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from β-cells and in glucagon secretion from α-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin–insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes. PMID:23535335

[Central nervous system dysgerminoma: a clinicopathological study of 3 cases].

PubMed

Bellil, Selma; Braham, Emna; Limaiem, Faten; Bellil, Khadija; Chelly, Ines; Mekni, Amina; Haouet, Slim; Zitouna, Moncef; Jemel, Hafedh; Khaldi, Moncef; Kchir, Nidhameddine

2009-03-01

Intracranial germ cell tumors are rarely seen and typically localize in the pineal or suprasellar region. The largest category of germ cell tumors is dysgerminoma. to describe clinicopathological features and immunohistochemical profile of dysgerminomas. We report three cases of central nervous system dysgerminomas. There were two young women and a man who were 6, 11 and 23-year-old. They presented with symptoms of insipidus diabetes (n=3) with association to visual field defects in the third case. Radiological findings showed a supra seller lesion in two cases. Double localization in the pineal and suprasellar regions was seen in the third case. Histologic examination and immunohistochemical study of surgical specimen were consistent with primary central nervous system dysgerminoma.

Is Migraine A Lateralisation Defect?

PubMed Central

Kaaro, Jani; Partonen, Timo; Naik, Paulami; Hadjikhani, Nouchine

2008-01-01

Migraine often co-occurs with patent foramen ovale (PFO) and some have suggested surgical closure as an efficient treatment for migraine. However, prospective studies do not report radical effect of PFO surgery on migraine. Here we examined the hypothesis that PFO and migraine may co-occur as two independent manifestations of lateralization defect during embryonic development. We measured the absolute displacement of a midline structure, the pineal gland, on brain scans of 39 migraineurs and 26 controls. We found a significant asymmetry of the pineal gland in migraineurs compared with controls. Our data suggest that migraine's circadian component and its association with PFO may be linked to a lateralization defect during embryogenesis, which could be a result from abnormal serotonin regulation. PMID:18695522

Melatonin effects on hard tissues: bone and tooth.

PubMed

Liu, Jie; Huang, Fang; He, Hong-Wen

2013-05-10

Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth.

Melatonin regulates somatotrope and lactotrope function through common and distinct signaling pathways in cultured primary pituitary cells from female primates.

PubMed

Ibáñez-Costa, Alejandro; Córdoba-Chacón, José; Gahete, Manuel D; Kineman, Rhonda D; Castaño, Justo P; Luque, Raúl M

2015-03-01

Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans.

Up-regulation of miR-325-3p suppresses pineal aralkylamine N-acetyltransferase (Aanat) after neonatal hypoxia-ischemia brain injury in rats.

PubMed

Yang, Yuanyuan; Sun, Bin; Huang, Jian; Xu, Lixiao; Pan, Jian; Fang, Chen; Li, Mei; Li, Gen; Tao, Yanfang; Yang, Xiaofeng; Wu, Ying; Miao, Po; Wang, Ying; Li, Hong; Ren, Jing; Zhan, Meiqin; Fang, Yiping; Feng, Xing; Ding, Xin

2017-08-01

Survivors of hypoxic-ischemic brain damage (HIBD), besides impairment of psychomotor development, often develop circadian rhythm disorders, although the underlying mechanisms are largely unknown. Here, we first verified that mRNA and protein expression of pineal aralkylamine N-acetyltransferase (Aanat), a key regulator for melatonin (MT) synthesis, along with MT, were severely impaired after HIBD. In addition, we demonstrated that neonatal HIBD disrupted the circadian rhythmicity of locomotor activities in juvenile rats. Based on bioinformatics analysis of a high throughput screening of miRNA expression changes after HIBD (Ding et al., 2015), we identified one microRNA, miR-325-3p, as a potential candidate responsible for the down regulation of Aanat after HIBD. Luciferase reporter assays demonstrated a specific interaction between miR-325-3p and Aanat mRNA 3'-UTR. miR-325-3p blocked norepinephrine (NE) induced Aanat activation in cultured pinealocytes. In addition, miR-325-3p inhibition partially rescued Aanat induction by NE, which was significantly reduced under oxygen glucose deprivation. By elucidating the role of pineal miR-325-3p on Aanat expression upon injury, our study provides new insights into the pathophysiological mechanisms of circadian dysfunction and potential therapeutic targets after HIBD. Copyright © 2017 Elsevier B.V. All rights reserved.

Methylphenidate-induced motor activity in rats: modulation by melatonin and vasopressin.

PubMed

Appenrodt, Edgar; Schwarzberg, Helmut

2003-04-01

Methylphenidate (MPH), a dopamine (DA) reuptake inhibitor, is well known to enhance motor activity, in part depending on the time of its application during the light-dark cycle. Moreover, after MPH administration, the hypothalamo-neurohypophysial axis including the neuropeptide vasopressin (AVP) was found influenced. Both the latter and behavioural effects of central AVP can also be modulated by the pineal gland with its light-dark-dependent activity. The present study was performed to investigate whether the pineal gland, its hormone melatonin (Mel), and AVP are involved in the MPH-evoked stimulation of activity. After application of 10 mg/kg MPH, the motor activity in pinealectomised (PE) rats was significantly higher than in sham-operated (SO) animals. After application of 250 microg Mel before MPH treatment, the stimulation of motor activity was diminished in PE rats and augmented in SO animals; however, when SO and PE rats were compared after Mel pretreatment, the reaction to MPH was nearly identical. Blocking the endogenous AVP by 25 or 1 microg of the V1a receptor antagonist d(CH(2))(5)[Tyr(Me)(2)]AVP (AAVP) before MPH treatment significantly augmented the motor activity in SO rats only and abolished the differences seen between SO and PE animals after MPH application. The present results indicate that the behavioural stimulation of MPH was modulated by both the pineal gland with its hormone Mel as well as the neuropeptide AVP.

Pineal Gland Calcification in Kurdistan: A Cross-Sectional Study of 480 Roentgenograms.

PubMed

Mohammed, Kahee A; Adjei Boakye, Eric; Ismail, Honer A; Geneus, Christian J; Tobo, Betelihem B; Buchanan, Paula M; Zelicoff, Alan P

2016-01-01

The goal of this study was to compare the incidence of Pineal Gland Calcification (PGC) by age group and gender among the populations living in the Kurdistan Region-Iraq. This prospective study examined skull X-rays of 480 patients between the ages of 3 and 89 years who sought care at a large teaching public hospital in Duhok, Iraq from June 2014 to November 2014. Descriptive statistics and a binary logistic regression were used for analysis. The overall incidence rate of PGC among the study population was 26.9% with the 51-60 age group and males having the highest incidence. PGC incidence increased after the first decade and remained steady until the age of 60. Thereafter the incidence began to decrease. Logistic regression analysis revealed that both age and gender significantly affected the risk of PGC. After adjusting for age, males were 1.94 (95% CI, 1.26-2.99) times more likely to have PGC compared to females. In addition, a one year increase in age increases the odds of developing PGC by 1.02 (95% CI, 1.01-1.03) units after controlling for the effects of gender. Our analysis demonstrated a close relationship between PGC and age and gender, supporting a link between the development of PGC and these factors. This study provides a basis for future researchers to further investigate the nature and mechanisms underlying pineal gland calcification.

p53 Restoration in Induction and Maintenance of Senescence: Differential Effects in Premalignant and Malignant Tumor Cells

PubMed Central

Harajly, Mohamad; Zalzali, Hasan; Nawaz, Zafar; Ghayad, Sandra E.; Ghamloush, Farah; Basma, Hussein; Zainedin, Samiha; Rabeh, Wissam; Jabbour, Mark; Tawil, Ayman; Badro, Danielle A.; Evan, Gerard I.

2015-01-01

The restoration of p53 has been suggested as a therapeutic approach in tumors. However, the timing of p53 restoration in relation to its efficacy during tumor progression still is unclear. We now show that the restoration of p53 in murine premalignant proliferating pineal lesions resulted in cellular senescence, while p53 restoration in invasive pineal tumors did not. The effectiveness of p53 restoration was not dependent on p19Arf expression but showed an inverse correlation with Mdm2 expression. In tumor cells, p53 restoration became effective when paired with either DNA-damaging therapy or with nutlin, an inhibitor of p53-Mdm2 interaction. Interestingly, the inactivation of p53 after senescence resulted in reentry into the cell cycle and rapid tumor progression. The evaluation of a panel of human supratentorial primitive neuroectodermal tumors (sPNET) showed low activity of the p53 pathway. Together, these data suggest that the restoration of the p53 pathway has different effects in premalignant versus invasive pineal tumors, and that p53 activation needs to be continually sustained, as reversion from senescence occurs rapidly with aggressive tumor growth when p53 is lost again. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene is intact but the pathway is inactive in the majority of examined tumors. PMID:26598601

Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats.

PubMed

Kim, Hye Sun; Paik, Man-Jeong; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

2015-01-01

We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on melatonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Urinary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Eight hours of nocturnal RFID exposure caused a significant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expression of AANAT were suppressed by exposure to RFID (p < 0. 05). Our results suggest that nocturnal RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

Co-expression of vesicular glutamate transporters (VGLUT1 and VGLUT2) and their association with synaptic-like microvesicles in rat pinealocytes.

PubMed

Morimoto, Riyo; Hayashi, Mitsuko; Yatsushiro, Shouki; Otsuka, Masato; Yamamoto, Akitsugu; Moriyama, Yoshinori

2003-01-01

A vesicular glutamate transporter (VGLUT) is responsible for the accumulation of l-glutamate in synaptic vesicles in glutamatergic neurons. Two isoforms, VGLUT1 and VGLUT2, have been identified, which are complementarily expressed in these neurons. Mammalian pinealocytes, endocrine cells for melatonin, are also glutamatergic in nature, accumulate l-glutamate in synaptic-like microvesicles (SLMVs), and secrete it through exocytosis. Although the storage of l-glutamate in SLMVs is mediated through a VGLUT, the molecular nature of the transporter is less understood. We recently observed that VGLUT2 is expressed in pinealocytes. In the present study, we show that pinealocytes also express VGLUT1. RT-PCR and northern blot analyses indicated expression of the VGLUT1 gene in pineal gland. Western blotting with specific antibodies against VGLUT1 indicated the presence of VGLUT1 in pineal gland. Indirect immunofluorescence microscopy with a section of pineal gland and cultured cells indicated that VGLUT1 and VGLUT2 are co-localized with process terminal regions of pinealocytes. Furthermore, immunoelectronmicroscopy as well as subcellular fractionation studies revealed that both VGLUT1 and VGLUT2 are specifically associated with SLMVs. These results indicate that both VGLUTs are responsible for storage of l-glutamate in SLMVs in pinealocytes. Pinealocytes are the first exception as to complementary expression of VGLUT1 and VGLUT2.

Hormones

MedlinePlus

Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure.

PubMed

Halgamuge, Malka N

2013-08-01

Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.

Impacts of moonlight on fish reproduction.

PubMed

Ikegami, Taro; Takeuchi, Yuki; Hur, Sung-Pyo; Takemura, Akihiro

2014-04-01

The waxing and waning cycle of the moon is repeated at approximately 1-month intervals, and concomitant changes occur in the levels of moonlight and cueing signals detected by organisms on the earth. In the goldlined spinefoot Siganus guttatus, a spawner lunar-synchronized around the first quarter moon, periodic changes in moonlight are used to cue gonadal development and gamete release. Rearing of mature fish under artificial constant full moon and new moon conditions during the spawning season leads to disruption or delay of synchronous spawning around the predicted moon phase. Melatonin, an endogenous transducer of the environmental light/dark cycle, increases in the blood and in the pineal gland around the new moon period and decreases around the full moon period. In synchrony with melatonin fluctuation, melatonin receptor(s) mRNA abundance is higher during the new moon period than during the full moon. The melatonin/melatonin receptor system is likely affected by moonlight. Measurements of the expression patterns of clock genes in neural tissues demonstrate that Cryptochrome (Cry1 and Cry3) and Period (Per2) fluctuate with lunar periodicity, the former peaking in the medial part of the brain around the first quarter moon period, and the latter peaking in the pineal gland around the full moon. Some clock genes may respond to periodic changes in moon phase and appear to be involved in the generation of lunar-related rhythmicity in lunar spawners. Thus, some fish use moonlight-related periodicities as reliable information for synchronizing the timing of reproductive events. Copyright © 2013 Elsevier B.V. All rights reserved.

The Pineal Gland

ERIC Educational Resources Information Center

Kimbrough, T. Daniel; Llewellyn, Gerald C.

1973-01-01

Describes a surgical technique for performing pinealectomics, applicable to classroom and laboratory studies, by using a head-holding device for small animals and a flat dissecting tray outfitted with holding straps for larger animals. (CC)

Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

ClinicalTrials.gov

2018-05-23

Childhood Brain Stem Neoplasm; Childhood Lymphoma; Childhood Solid Neoplasm; Pineal Region Neoplasm; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Visual Pathway Glioma; Refractory Central Nervous System Neoplasm

Pineal melatonin and the innate immune response: the TNF-alpha increase after cesarean section suppresses nocturnal melatonin production.

PubMed

Pontes, Gerlândia N; Cardoso, Elaine C; Carneiro-Sampaio, Magda M S; Markus, Regina P

2007-11-01

The nocturnal surge of melatonin is the endocrine expression of the circadian system and is essential for organizing the timing of various endogenous processes. Previous works suggest that, in the beginning of a defense response, the increase in circulating tumor necrosis factor-alpha (TNF-alpha) leads to a transient block of nocturnal melatonin production and promotes a disruption of internal time organization. In the present paper, the concentration of melatonin and cytokines [TNF-alpha, interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12] in the colostrum (postdelivery day 3) and in the milk (postdelivery days 10, 15, 20 and 30) obtained at midday and midnight from mothers who gave birth by vaginal or cesarean section were compared. The nocturnal melatonin surge observed 3 days after vaginal delivery was absent after cesarean section. IL-12 presented no daily variation in either case, while daily variations in IFN-gamma, IL-10, IL-4 and IL-5 were observed after vaginal delivery and cesarean section. On the other hand, the increase in TNF-alpha after cesarean section resulted in suppression of the nocturnal melatonin surge. Daily variation of IL-2 was only observed after recovery of the nocturnal melatonin surge, 30 days after cesarean section. The present paper supports the hypothesis of a cross-talk between the pineal gland and the immune system, which could represent a putative immune-pineal axis.

[Protective effect of melatonin and epithalon on hypothalamic regulation of reproduction in female rats in its premature aging model and on estrous cycles in senescent animals in various lighting regimes].

PubMed

Korenevsky, A V; Milyutina, Yu P; Bukalyov, A V; Baranova, Yu P; Vinogradova, I A; Arutjunyan, A V

2013-01-01

Potential neuroprotective effects of the pineal gland hormone melatonin and peptide preparation epitalon on estrous cycles and the central regulation of reproduction in female rats exposed to unfavourable environmental factors have been studied. Estrous cycles of young, mature and aging rats exposed to light pollution were described. The diurnal dynamics and daily mean content of biogenic amines in the hypothalamic areas responsible for gonadotropin-releasing hormone synthesis and secretion in animals of different age groups were investigated. An effect of a chemical factor on the noradrenergic system of the medial preoptic area and on the dopaminergic system of the median eminence with arcuate nuclei of the hypothalamus was studied in premature aging of reproduction model. Administration of the pineal gland peptide melatonin and peptide preparation epitalon was shown to be able to correct a number of impairments of the hypothalamic-pituitary-gonadal axis that can be observed, when the experimental animals were exposed to permanent artificial lighting and a neurotoxic xenobiotic 1,2-dimethylhydrazine. The data obtained testify to an important role of the pineal gland in the circadian signal formation needed for gonadotropin-releasing hormone in order to exert its preovulatory peak secretion and to the protective effect of melatonin and epitalon, which are able to reduce unfavourable environmental influences on reproduction of young and aging female rats.

Outcome of single-trajectory rigid endoscopic third ventriculostomy and biopsy in the management algorithm of pineal region tumors: a case series and review of the literature.

PubMed

Abbassy, Mahmoud; Aref, Khaled; Farhoud, Ahmed; Hekal, Anwar

2018-05-28

Tumors within the pineal region represent 1.5 to 8.5% of the pediatric brain tumors and 1.2% of all brain tumors. A management algorithm has been proposed in several publications. The algorithm includes endoscopic third ventriculostomy (ETV) and biopsy in cases presenting with hydrocephalus. In this series, we are presenting the efficacy of a single-trajectory approach for both ETV and biopsy. Eleven cases were admitted to Alexandria main university hospital from 2013 to 2016 presenting with pineal region tumors and hydrocephalus. Mean age at diagnosis was 11 years (1-27 years). All cases had ETV and biopsy using rigid ventriculoscope through a single trajectory from a burr hole planned on preoperative imaging. Follow-up period was 7-48 months. All 11 cases presented with hydrocephalus and increased intracranial pressure manifestations. Histopathological diagnosis was successful in 9 out of 11 cases (81.8%). Three cases were germ-cell tumors, two cases were pineoblastomas, two cases were pilocytic astrocytomas, and two cases were grade 2 tectal gliomas. Five of the ETV cases (45.5%) failed and required VPS later on. Other complications of ETV included one case of intraventricular hemorrhage and a case with tumor disseminated to the basal cisterns. In our series, we were able to achieve ETV and biopsy through a single trajectory and a rigid endoscope with results comparable to other studies in the literature.

The study of the wonderful: the first topographical mapping of vision in the brain.

PubMed

Fishman, Ronald S

2008-12-01

The conception by René Descartes of the human brain, notorious as it is for placing the soul or mind in the pineal gland, had yet within it the basic idea of the brain as a highly organized mechanism with topographical sensory mapping and different functions localized in specific areas. Descartes was directly led to this idea by his appreciation of what the retinal image conceived by Johannes Kepler implied, not only for the nature of vision, but for the operation of the brain in general. The linkage between Kepler and Descartes is not widely appreciated but is one of the best examples of synergism in the history of science.

THE ROLE OF THE PINEAL GLAND AND OF ENVIRONMENTAL LIGHTING IN THE REGULATION OF THE ENDOCRINE AND REPRODUCTIVE SYSTEMS OF RODENTS.

DTIC Science & Technology

PHOTOPERIODISM, REPRODUCTION(PHYSIOLOGY)), (*ENDOCRINE GLANDS , REPRODUCTION(PHYSIOLOGY)), RODENTS, REPRODUCTIVE SYSTEM, EYE, EXCISION, TESTES, OVARIES, ADRENAL GLANDS , THYROID GLAND , IODINE, THIOUREA, RATS, HAMSTERS

Childhood Central Nervous System Embryonal Tumors Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood central nervous system embryonal tumors and pineal tumors are treated with surgery, radiation therapy, chemotherapy, high-dose chemotherapy with stem cell rescue and targeted therapy. Learn more in this expert-reviewed summary.

Reduced sympathetic innervation after alteration of target cell neurotransmitter phenotype in transgenic mice.

PubMed Central

Cho, S; Son, J H; Park, D H; Aoki, C; Song, X; Smith, G P; Joh, T H

1996-01-01

Neurotransmitters play a variety of important roles during nervous system development. In the present study, we hypothesized that neurotransmitter phenotype of both projecting and target cells is an important factor for the final synaptic linkage and its specificity. To test this hypothesis, we used transgenic techniques to convert serotonin/melatonin-producing cells of the pineal gland into cells that also produce dopamine and investigated the innervation of the phenotypically altered target cells. This phenotypic alteration markedly reduced the noradrenergic innervation originating from the superior cervical ganglia. Although the mechanism by which the reduction occurs is presently unknown, quantitative enzyme-linked immunoassay showed the presence of the equivalent amounts of nerve growth factor (NGF) in the control and transgenic pineal glands, suggesting that it occurred in a NGF-independent manner. The results suggest that target neurotransmitter phenotype influences the formation of afferent connections during development. Images Fig. 3 Fig. 4 PMID:8610132

Melatonin and Ischemic Stroke: Mechanistic Roles and Action.

PubMed

Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

2015-01-01

Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca(2+) level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

Melatonin and Ischemic Stroke: Mechanistic Roles and Action

PubMed Central

Andrabi, Syed Suhail; Tabassum, Heena

2015-01-01

Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke. PMID:26435711

Local Actions of Melatonin in Somatic Cells of the Testis

PubMed Central

Frungieri, Mónica Beatriz; Calandra, Ricardo Saúl; Rossi, Soledad Paola

2017-01-01

The pineal hormone melatonin regulates testicular function through the hypothalamic-adenohypophyseal axis. In addition, direct actions of melatonin in somatic cells of the testis have been described. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular growth, proliferation, energy metabolism and the oxidation state, and consequently may regulate spermatogenesis. These data pinpoint melatonin as a key player in the regulation of testicular physiology (i.e., steroidogenesis, spermatogenesis) mostly in seasonal breeders. In patients with idiopathic infertility, melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, and provides protective effects against oxidative stress in testicular mast cells. Consequently, melatonin is also involved in the modulation of inflammatory and oxidant/anti-oxidant states in testicular pathology. Overall, the literature data indicate that melatonin has important effects on testicular function and male reproduction. PMID:28561756

Effect of K+ and Na+ on calcium-dependent electron-dense particles in the monoaminergic synaptic vesicles of rat pineal nerves fixed in Ca2+-containing solutions.

PubMed

Pellegrino de Iraldi, A; Corazza, J P

1983-01-01

The effect of K+ and Na+ on the Ca2+ binding site in the dense core of monoaminergic vesicles of pineal nerves was investigated in the rat. Rat pineal glands, bisected immediately after decapitation, were incubated at room temperature in solutions containing high K+ or high Na+ in the presence or absence of Ca2+. Fixation was performed in glutaraldehyde-osmium tetroxide in collidine buffer, with and without CaCl2. It was confirmed that, after fixation in Ca2+-containing solutions, an electron-dense particle, located in the vesicle core, which can be considered a calcium deposit, appears within the synaptic vesicles. It was observed that this Ca2+ deposit may be modified by incubation in a high K+ or high Na+ milieu before fixation in Ca2+ containing solutions. When the incubation was carried out with high K+ and high Ca2+ simultaneously, Ca2+ deposits were considerably increased. With K+ alone, no Ca2+ deposits were apparent, as when electrical stimulation is applied before fixation. This effect was not observed when the incubation was done in high Na+. Consecutive incubations in high K+ and high Na+, respectively, restored the capability of the vesicle cores to bind Ca2+. Prolonged incubation in high Na+ before fixation increased Ca2+ deposits within the vesicles. These findings are in line with data on the effect of these ions upon the storage and release of biogenic amines and suggest that these ions modify the capability of synaptic vesicles to bind Ca2+.

Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

ClinicalTrials.gov

2015-05-29

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

Extraretinal Light Perception in the Sparrow, III: The Eyes Do Not Participate in Photoperiodic Photoreception*

PubMed Central

Menaker, Michael; Roberts, Richard; Elliott, Jeffrey; Underwood, Herbert

1970-01-01

Photoperiodic control of testis growth in Passer domesticus (house sparrow) is mediated entirely by extraretinal photoreceptors in the brain. The eyes do not participate in photoperiodically significant photoreception. Removal of the pineal organ does not affect either the response to light or, to a first approximation, the process of recrudescence. The intensity of light reaching the retina and that reaching the extraretinal photoreceptor were varied independently. This technique will make it possible to study brain photoreception in species of birds that will not tolerate blinding. Extreme caution is necessary in the interpretation of brain lesion experiments in which reproductive function is modified, since photoreception by brain receptors of unknown anatomical location affects testicular state. PMID:5272320

The habenula.

PubMed

Namboodiri, Vijay Mohan K; Rodriguez-Romaguera, Jose; Stuber, Garret D

2016-10-10

The habenula is a tiny brain region the size of a pea in humans. This region is highly conserved across vertebrates and has been traditionally overlooked by neuroscientists. The name habenula is derived from the Latin word habena, meaning "little rein", because of its elongated shape. Originally its function was thought to be related to the regulation of the nearby pineal gland (which Rene Descartes described as the "principal seat of the soul"). More recent evidence, however, demonstrates that the habenula acts as a critical neuroanatomical hub that connects and regulates brain regions important for divergent motivational states and cognition. In this Primer, we will discuss the recent and converging evidence that points to the habenula as a key brain region for motivation and decision-making. Copyright © 2016. Published by Elsevier Ltd.

The neural code of thoughts and feelings. Comment on "Topodynamics of metastable brains" by Arturo Tozzi et al.

NASA Astrophysics Data System (ADS)

Jaušovec, Norbert

2017-07-01

Recently the number of theories trying to explain the brain - cognition - behavior relation has been increased. Promoted on the one hand by the development of sophisticated brain imaging techniques, such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), and on the other, by complex computational models based on chaos and graph theory. But has this really advanced our understanding of the brain-behavior relation beyond Descartes's dualistic mind body division? One could critically argue that replacing the pineal body with extracellular electric fields represented in the electroencephalogram (EEG) as rapid transitional processes (RTS), combined with algebraic topology and dubbed brain topodynamics [1] is just putting lipstick on an outmoded evergreen.

Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

ClinicalTrials.gov

2015-12-14

Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

PubMed

Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

2006-11-01

Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

PubMed

Zatz, M; Mullen, D A

1988-11-01

We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls.

PubMed

Bumb, Jan Malte; Mier, Daniela; Noelte, Ingo; Schredl, Michael; Kirsch, Peter; Hennig, Oliver; Liebrich, Luisa; Fenske, Sabrina; Alm, Barbara; Sauer, Carina; Leweke, Franz Markus; Sobanski, Esther

2016-07-01

The pineal gland, as part of the human epithalamus, is the main production site of peripheral melatonin, which promotes the modulation of sleep patterns, circadian rhythms and circadian preferences (morningness vs. eveningness). The present study analyses the pineal gland volume (PGV) and its association with circadian preferences and symptom severity in adult ADHD patients compared to healthy controls. PGV was determined manually using high-resolution 3T MRI (T1-magnetization prepared rapid gradient echo) in medication free adult ADHD patients (N=74) compared to healthy controls (N=86). Moreover, the Morningness-Eveningness Questionnaire (MEQ), the ADHD Diagnostic Checklist and the Wender-Utah Rating Scale were conducted. PGV differed between both groups (patients: 59.9±33.8mm(3); healthy controls: 71.4±27.2mm(3), P=0.04). In ADHD patients, more eveningness types were revealed (patients: 29%; healthy controls: 17%; P=0.05) and sum scores of the MEQ were lower (patients: 45.8±11.5; healthy controls 67.2±10.1; P<0.001). Multiple regression analyses indicated a positive correlation of PGV and MEQ scores in ADHD (β=0.856, P=0.003) but not in healthy controls (β=0.054, P=0.688). Patients' MEQ scores (β=-0.473, P=0.003) were negatively correlated to ADHD symptoms. The present results suggest a linkage between the PGV and circadian preference in adults with ADHD and an association of the circadian preference to symptom severity. This may facilitate the development of new chronobiological treatment approaches for the add-on treatment in ADHD. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Endoscopic versus stereotactic procedure for pineal tumour biopsies: Comparative review of the literature and learning from a 25-year experience.

PubMed

Balossier, A; Blond, S; Touzet, G; Lefranc, M; de Saint-Denis, T; Maurage, C-A; Reyns, N

2015-01-01

Pineal tumours account for 1% to 4% of brain tumours in adults and for around 10% in children. Except in a few cases where germ cell markers are elevated, accurate histological samples are mandatory to initiate the treatment. Open surgery still has a high morbidity and is often needless. Biopsies can either be obtained by endoscopic or stereotactic procedures. Following an extensive review of the literature (PubMed 1970-2013; keywords pineal tumour, biopsy; English and French), 33 studies were analysed and relevant data compared regarding the type of procedure, diagnosis rate, cerebrospinal fluid diversion type and rate, perioperative mortality, morbidity. Endoscopic and stereotactic biopsies showed a diagnosis rate of 81.1% (20%-100%) and 93.7% (82%-100%), respectively. Endoscopic biopsies involved 21.0% of minor and 2.0% of major complications whereas stereotactic biopsies involved 6.4% of minor and 1.6% of major complications. The most frequently reported complication was haemorrhage for both endoscopic and stereotactic procedures, accounting for 4.8% and 4.3%, respectively. Mortality rate was low for both endoscopic and stereotactic procedures, equal to 0.4% and 1.3%, respectively. Local experience of stereotactic biopsies was also reported and corroborated the previous data. The difference between both procedures is not statistically significant (p>0.05) across large series (≥20patients). Nevertheless, tissue diagnosis appears less accurate with endoscopic procedures than with stereotactic procedures (81.1% versus 93.7%, weighted mean across all series). In our opinion, the neuroendoscopic approach is the best tool for managing hydrocephalus, whereas stereotactic biopsies remain the best way to obtain a tissue diagnosis with accuracy and low morbidity. Copyright © 2014. Published by Elsevier Masson SAS.

Novel somatic and germline mutations in intracranial germ cell tumours.

PubMed

Wang, Linghua; Yamaguchi, Shigeru; Burstein, Matthew D; Terashima, Keita; Chang, Kyle; Ng, Ho-Keung; Nakamura, Hideo; He, Zongxiao; Doddapaneni, Harshavardhan; Lewis, Lora; Wang, Mark; Suzuki, Tomonari; Nishikawa, Ryo; Natsume, Atsushi; Terasaka, Shunsuke; Dauser, Robert; Whitehead, William; Adekunle, Adesina; Sun, Jiayi; Qiao, Yi; Marth, Gábor; Muzny, Donna M; Gibbs, Richard A; Leal, Suzanne M; Wheeler, David A; Lau, Ching C

2014-07-10

Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

Novel somatic and germline mutations in intracranial germ cell tumors

PubMed Central

Wang, Linghua; Yamaguchi, Shigeru; Burstein, Matthew D.; Terashima, Keita; Chang, Kyle; Ng, Ho-Keung; Nakamura, Hideo; He, Zongxiao; Doddapaneni, Harshavardhan; Lewis, Lora; Wang, Mark; Suzuki, Tomonari; Nishikawa, Ryo; Natsume, Atsushi; Terasaka, Shunsuke; Dauser, Robert; Whitehead, William; Adekunle, Adesina; Sun, Jiayi; Qiao, Yi; Marth, Gábor; Muzny, Donna M.; Gibbs, Richard A.; Leal, Suzanne M.; Wheeler, David A.; Lau, Ching C.

2015-01-01

Intracranial germ cell tumors (IGCTs) are a group of rare heterogeneous brain tumors which are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographic and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically 5–8 fold greater in Japan and other East Asian countries than in Western countries1 with peak incidence near the time of puberty2. About half of the tumors are located in the pineal region. The male-to-female incidence ratio is approximately 3–4:1 overall but even higher for tumors located in the pineal region3. Due to the scarcity of tumor specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next generation sequencing, SNP array and expression array. We find the KIT/RAS signaling pathway frequently mutated in over 50% of IGCTs including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gain of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional corepressor and tumor suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, a histone demethylase and coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway. PMID:24896186

Stereotactic Radiosurgery in Treating Patients With Brain Tumors

ClinicalTrials.gov

2012-03-21

Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

9 CFR 318.1 - Products and other articles entering official establishments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... substance shall be brought into or kept in an official establishment. (f) [Reserved] (g) Glands and organs, such as cotyledons, ovaries, prostate glands, tonsils, spinal cords, and detached lymphatic, pineal, pituitary, parathyroid, suprarenal, pancreatic and thyroid glands, used in preparing pharmaceutical...

9 CFR 318.1 - Products and other articles entering official establishments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... substance shall be brought into or kept in an official establishment. (f) [Reserved] (g) Glands and organs, such as cotyledons, ovaries, prostate glands, tonsils, spinal cords, and detached lymphatic, pineal, pituitary, parathyroid, suprarenal, pancreatic and thyroid glands, used in preparing pharmaceutical...

9 CFR 318.1 - Products and other articles entering official establishments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... substance shall be brought into or kept in an official establishment. (f) [Reserved] (g) Glands and organs, such as cotyledons, ovaries, prostate glands, tonsils, spinal cords, and detached lymphatic, pineal, pituitary, parathyroid, suprarenal, pancreatic and thyroid glands, used in preparing pharmaceutical...

9 CFR 318.1 - Products and other articles entering official establishments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... substance shall be brought into or kept in an official establishment. (f) [Reserved] (g) Glands and organs, such as cotyledons, ovaries, prostate glands, tonsils, spinal cords, and detached lymphatic, pineal, pituitary, parathyroid, suprarenal, pancreatic and thyroid glands, used in preparing pharmaceutical...

9 CFR 318.1 - Products and other articles entering official establishments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... substance shall be brought into or kept in an official establishment. (f) [Reserved] (g) Glands and organs, such as cotyledons, ovaries, prostate glands, tonsils, spinal cords, and detached lymphatic, pineal, pituitary, parathyroid, suprarenal, pancreatic and thyroid glands, used in preparing pharmaceutical...

The circumventricular organs: an atlas of comparative anatomy and vascularization.

PubMed

Duvernoy, Henri M; Risold, Pierre-Yves

2007-11-01

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism.

PubMed

Laranjeira-Silva, Maria Fernanda; Zampieri, Ricardo A; Muxel, Sandra M; Floeter-Winter, Lucile Maria; Markus, Regina P

2015-11-01

Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin receptors with luzindole, whereas melatonin treatment during the light phase attenuated Leishmania infection. In vitro studies corroborated in vivo observations. Melatonin treatment reduced macrophage expression of Cat-2b, Cat1, and ArgI, genes involved in arginine uptake and polyamine synthesis. Indeed, melatonin reduced macrophage arginine uptake by 40%. Putrescine supplementation reverted the attenuation of infectivity by melatonin indicating that its effect was due to the arrest of parasite replication. This study shows that the Leishmania/host interaction varies in a circadian manner according to nocturnal melatonin pineal synthesis. Our results provide new data regarding Leishmania infectiveness and show new approaches for applying agonists of melatonin receptors in Leishmaniasis therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of the pineal gland and melatonin on blood flow and evaporative water loss during heat stress in rats.

PubMed

Harlow, H J

1987-01-01

Plasma melatonin levels of laboratory rats were elevated both during acute heat exposure (43 degrees C for 40 min) and chronic exposure (33 degrees C for 17 days) suggesting a possible correlation between melatonin and thermoregulatory mechanisms. Pinealectomy reduced the nighttime elevation in oxygen consumption and evaporative water loss. In addition, pinealectomized animals exhibited a significantly lower cutaneous evaporative water loss both at night and during the day when exposed to an acute heat exposure of 38 degrees C for 45 min. Pinealectomy elevated the blood pressure over the control group whereas melatonin infusion depressed the blood pressure without altering the cardiac output. This relationship implies an action by melatonin on the peripheral vasculature. In support of this conclusion, melatonin pretreatment tended to dampen the vasopressive effect of infused norepinephrine. These data, therefore, suggest a role of the pineal gland and melatonin in thermoregulation through an influence on the cardiovascular system and evaporative water loss.

Lack of circadian regulation of melatonin rhythms in the sockeye salmon (Oncorhynchus nerka) in vivo and in vitro.

PubMed

Iigo, Masayuki; Azuma, Teruo; Iwata, Munehico

2007-01-01

Melatonin profiles were determined in the plasma in vivo and in the pineal organ in vitro of the sockeye salmon (Oncorhynchus nerka) under various light conditions to test whether they are under circadian regulation. When serial blood samples were taken at 4-h intervals for 3 days via a cannula inserted into the dorsal aorta, plasma melatonin exhibited significant fluctuation under a light-dark cycle, with higher levels during the dark phase than during the light phase. No rhythmic fluctuations persisted under either constant dark or constant light, with constant low and high levels, respectively. Melatonin release from the pineal organ in flow-through culture exhibited a similar pattern in response to the change in light conditions, with high and low release associated with the dark and light phases, respectively. These results indicate that melatonin production in the sockeye salmon is driven by light and darkness but lacks circadian regulation.

Disruption of retinoid-related orphan receptor beta changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice.

PubMed Central

André, E; Conquet, F; Steinmayr, M; Stratton, S C; Porciatti, V; Becker-André, M

1998-01-01

The orphan nuclear receptor RORbeta is expressed in areas of the central nervous system which are involved in the processing of sensory information, including spinal cord, thalamus and sensory cerebellar cortices. Additionally, RORbeta localizes to the three principal anatomical components of the mammalian timing system, the suprachiasmatic nuclei, the retina and the pineal gland. RORbeta mRNA levels oscillate in retina and pineal gland with a circadian rhythm that persists in constant darkness. RORbeta-/- mice display a duck-like gait, transient male incapability to sexually reproduce, and a severely disorganized retina that suffers from postnatal degeneration. Consequently, adult RORbeta-/- mice are blind, yet their circadian activity rhythm is still entrained by light-dark cycles. Interestingly, under conditions of constant darkness, RORbeta-/- mice display an extended period of free-running rhythmicity. The overall behavioral phenotype of RORbeta-/- mice, together with the chromosomal localization of the RORbeta gene, suggests a close relationship to the spontaneous mouse mutation vacillans described >40 years ago. PMID:9670004

Circadian changes in long noncoding RNAs in the pineal gland

PubMed Central

Coon, Steven L.; Munson, Peter J.; Cherukuri, Praveen F.; Sugden, David; Rath, Martin F.; Møller, Morten; Clokie, Samuel J. H.; Fu, Cong; Olanich, Mary E.; Rangel, Zoila; Werner, Thomas; Mullikin, James C.; Klein, David C.; Benjamin, Betty; Blakesley, Robert; Bouffard, Gerry; Brooks, Shelise; Chu, Grace; Coleman, Holly; Dekhtyar, Mila; Gregory, Michael; Guan, Xiaobin; Gupta, Jyoti; Han, Joel; Hargrove, April; Ho, Shi-ling; Johnson, Taccara; Legaspi, Richelle; Lovett, Sean; Maduro, Quino; Masiello, Cathy; Maskeri, Baishali; McDowell, Jenny; Montemayor, Casandra; Novotny, Betsy; Park, Morgan; Riebow, Nancy; Schandler, Karen; Schmidt, Brian; Sison, Christina; Stantripop, Mal; Thomas, James; Vemulapalli, Meg; Young, Alice

2012-01-01

Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the rat pineal gland, which is the source of melatonin, the hormone of the night. Approximately one-half of these changes reflect nocturnal increases. Studies of eight lncRNAs with 2- to >100-fold daily rhythms indicate that, in most cases, the change results from neural stimulation from the central circadian oscillator in the suprachiasmatic nucleus (doubling time = 0.5–1.3 h). Light exposure at night rapidly reverses (halving time = 9–32 min) levels of some of these lncRNAs. Organ culture studies indicate that expression of these lncRNAs is regulated by norepinephrine acting through cAMP. These findings point to a dynamic role of lncRNAs in the circadian system. PMID:22864914

Interaction and developmental activation of two neuroendocrine systems that regulate light-mediated skin pigmentation.

PubMed

Bertolesi, Gabriel E; Song, Yi N; Atkinson-Leadbeater, Karen; Yang, Jung-Lynn J; McFarlane, Sarah

2017-07-01

Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion. As embryogenesis proceeds, the pineal complex/melatonin circuit becomes the dominant regulator in the dark and induces lightening of the skin of larvae. The eye/α-MSH circuit continues to mediate darkening of embryos on a black background, but we propose the circuit is shut down in complete darkness in part by melatonin acting on receptors expressed by pituitary cells to inhibit the expression of pomc, the precursor of α-MSH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Light pollution: the possible consequences of excessive illumination on retina.

PubMed

Contín, M A; Benedetto, M M; Quinteros-Quintana, M L; Guido, M E

2016-02-01

Light is the visible part of the electromagnetic radiation within a range of 380-780 nm; (400-700 on primates retina). In vertebrates, the retina is adapted to capturing light photons and transmitting this information to other structures in the central nervous system. In mammals, light acts directly on the retina to fulfill two important roles: (1) the visual function through rod and cone photoreceptor cells and (2) non-image forming tasks, such as the synchronization of circadian rhythms to a 24 h solar cycle, pineal melatonin suppression and pupil light reflexes. However, the excess of illumination may cause retinal degeneration or accelerate genetic retinal diseases. In the last century human society has increased its exposure to artificial illumination, producing changes in the Light/Dark cycle, as well as in light wavelengths and intensities. Although, the consequences of unnatural illumination or light pollution have been underestimated by modern society in its way of life, light pollution may have a strong impact on people's health. The effects of artificial light sources could have direct consequences on retinal health. Constant exposure to different wavelengths and intensities of light promoted by light pollution may produce retinal degeneration as a consequence of photoreceptor or retinal pigment epithelium cells death. In this review we summarize the different mechanisms of retinal damage related to the light exposure, which generates light pollution.

Light pollution: the possible consequences of excessive illumination on retina

PubMed Central

Contín, M A; Benedetto, M M; Quinteros-Quintana, M L; Guido, M E

2016-01-01

Light is the visible part of the electromagnetic radiation within a range of 380–780 nm; (400–700 on primates retina). In vertebrates, the retina is adapted to capturing light photons and transmitting this information to other structures in the central nervous system. In mammals, light acts directly on the retina to fulfill two important roles: (1) the visual function through rod and cone photoreceptor cells and (2) non-image forming tasks, such as the synchronization of circadian rhythms to a 24 h solar cycle, pineal melatonin suppression and pupil light reflexes. However, the excess of illumination may cause retinal degeneration or accelerate genetic retinal diseases. In the last century human society has increased its exposure to artificial illumination, producing changes in the Light/Dark cycle, as well as in light wavelengths and intensities. Although, the consequences of unnatural illumination or light pollution have been underestimated by modern society in its way of life, light pollution may have a strong impact on people's health. The effects of artificial light sources could have direct consequences on retinal health. Constant exposure to different wavelengths and intensities of light promoted by light pollution may produce retinal degeneration as a consequence of photoreceptor or retinal pigment epithelium cells death. In this review we summarize the different mechanisms of retinal damage related to the light exposure, which generates light pollution. PMID:26541085

Exposure chamber for determining the biological effects of electric and magnetic fields on dairy cows.

PubMed

Nguyen, Duc Hai; Richard, Louis; Burchard, Javier F

2005-02-01

An exposure chamber was designed to study the effects of electric and magnetic fields (EMF) on oestrous cycles, hormonal profile during gestation, pineal function, quantity and quality of milk production, feed intake, and central nervous system of dairy cattle. The chamber was 15 x 10 x 3 m; and the control system was fully computerized so that the field intensities can be varied and monitored continuously, on site or remotely. During exposure to EMF, milk production, feed consumption, and health were monitored closely and blood and cerebral spinal fluid were continuously sampled. The chamber characteristics allow use of a wide range of exposure such as electric fields (0-30 kV/m) and magnetic fields (0-100 microT) at frequencies ranging from 45 to 3000 Hz.

MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS

EPA Science Inventory

There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

Melatonin increases reactive aggression in humans.

PubMed

Liu, Jinting; Zhong, Ru; Xiong, Wei; Liu, Haibo; Eisenegger, Christoph; Zhou, Xiaolin

2017-10-01

Melatonin, a hormone released preferentially by the pineal gland during the night, affects circadian rhythms and aging processes. As animal studies have shown that melatonin increases resident-intruder aggression, this study aimed to investigate the impact of melatonin treatment on human aggression. In a double-blind, randomized, placebo-controlled between-participant design, 63 healthy male volunteers completed the Taylor Aggression Paradigm (TAP) after oral administration of melatonin or placebo. We found that when given the opportunity to administer high or low punishments to an opponent, participants who ingested melatonin selected the high punishment more often than those who ingested placebo. The increased reactive aggression under melatonin administration remained after controlling for inhibitory ability, trait aggression, trait impulsiveness, circadian preference, perceptual sensibility to noise, and changes in subjective sleepiness and emotional states. This study provides novel and direct evidence for the involvement of melatonin in human social processes.

Melatonin in children with autistic spectrum disorders: recent and practical data.

PubMed

Doyen, C; Mighiu, D; Kaye, K; Colineaux, C; Beaumanoir, C; Mouraeff, Y; Rieu, C; Paubel, P; Contejean, Y

2011-05-01

Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants.

PubMed

Nieto-Sampedro, Manuel

2003-11-01

Growth-promoting macroglia (aldynoglia) with growth properties and immunological markers similar to Schwann cells, are found in loci of the mammalian CNS where axon regeneration occurs throughout life, like the olfactory sytem, hypothalamus-hypophysis and the pineal gland. Contrary to Schwann cells, aldynoglia mingle freely with astrocytes and can migrate in brain and spinal cord. Transplantation of cultured and immunopurified olfactory ensheathing cells (OECs) in the spinal cord after multiple central rhizotomy, promoted sensory and central axon growth and partial functional restoration, judging by anatomical, electrophysiological and behavioural criteria. OEC transplants suppressed astrocyte reactivity, thus generally favouring axon growth after a lesion. However, the functional repair promoted by OEC transplants was partial in the best cases, depending on lesion type and location. Cyst formation after photochemical cord lesion was partially prevented but neither the corticospinal tract, interrupted by a mild contusion, nor the sectioned medial longitudinal fascicle, did regrow after OEC transplantation in the injured area.

A review of sleep disorders and melatonin.

PubMed

Xie, Zizhen; Chen, Fei; Li, William A; Geng, Xiaokun; Li, Changhong; Meng, Xiaomei; Feng, Yan; Liu, Wei; Yu, Fengchun

2017-06-01

Sleep disorders are a group of conditions that affect the ability to sleep well on a regular basis and cause significant impairments in social and occupational functions. Although currently approved medications are efficacious, they are far from satisfactory. Benzodiazepines, antidepressants, antihistamines and anxiolytics have the potential for dependence and addiction. Moreover, some of these medications can gradually impair cognition. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone produced by the pineal gland and released exclusively at night. Exogenous melatonin supplementation is well tolerated and has no obvious short- or long-term adverse effects. Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep. It is centrally involved in anti-oxidation, circadian rhythmicity maintenance, sleep regulation and neuronal survival. This narrative review aims to provide a comprehensive overview of various therapeutic functions of melatonin in insomnia, sleep-related breathing disorders, hypersomnolence, circadian rhythm sleep-wake disorders and parasomnias. Melatonin offers an alternative treatment to the currently available pharmaceutical therapies for sleep disorders with significantly less side effects.

Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

ClinicalTrials.gov

2017-10-25

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

[Melatonin as a universal stabilizing factor of mental activity].

PubMed

Arushanian, Ē B

2011-01-01

Pineal hormone melatonin stabilizes mental activity of man and animals due to its somnogenic, anxiolytic, antidepressant and nootropic properties. Melatonin effects are based on the synchronization of biological rhythms via the influence on the cerebral structures which control biological rhythms and emotions and normalize endocrine and immune state.

Melatonin: A Cutaneous Perspective on its Production, Metabolism, and Functions.

PubMed

Slominski, Andrzej T; Hardeland, Ruediger; Zmijewski, Michal A; Slominski, Radomir M; Reiter, Russel J; Paus, Ralf

2018-03-01

Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. Although melatonin is best known to regulate circadian rhythmicity and lower vertebrate skin pigmentation, the full spectrum of functional activities of this free radical-scavenging molecule, which also induces/promotes complex antioxidative and DNA repair systems, includes immunomodulatory, thermoregulatory, and antitumor properties. Because this plethora of functional melatonin properties still awaits to be fully appreciated by dermatologists, the current review synthesizes the main features that render melatonin a promising candidate for the management of several dermatoses associated with substantial oxidative damage. We also review why melatonin promises to be useful in skin cancer prevention, skin photo- and radioprotection, and as an inducer of repair mechanisms that facilitate the recovery of human skin from environmental damage. The fact that human skin and hair follicles not only express functional melatonin receptors but also engage in substantial, extrapineal melatonin synthesis further encourages one to systematically explore how the skin's melatonin system can be therapeutically targeted in future clinical dermatology and enrolled for preventive medicine strategies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Melatonin: aeromedical, toxicopharmacological, and analytical aspects.

PubMed

Sanders, D C; Chaturvedi, A K; Hordinsky, J R

1999-01-01

Melatonin, a pineal hormone present in the blood of humans and other species, has a distinct diurnal variation in its biosynthesis and, therefore, in its concentration. This variation has suggested the possibility of a regulatory function in day/night-dependent physiological processes such as sleep and has led scientists to explore the effects of administered melatonin on the modulation of circadian rhythms. For the self-treatment of sleep disorders and other benefits, melatonin use has been extolled to the extent that 20 million new consumers were added to the U.S. retail market in 1995. Its principal aeromedical application has been in the experimental treatment of jet-lag effects. For aircraft passengers, melatonin administration at destination bedtime appears to improve sleep quality and to decrease the time required to reestablish normal circadian rhythms. For international aircrews that travel through multiple time zones without time to adapt to new environments, taking melatonin before arriving home may further impair already disturbed circadian rhythms. Its use to adjust to shiftwork changes by air traffic controllers, aircraft maintenance workers, and support personnel is even more controversial. Limited studies suggest that giving this hormone to shift workers should be done only under controlled conditions and that taking it at the wrong time may actually impair job performance. Because of its possible interaction with certain medications and the changes in its concentrations observed in some clinical conditions, the practitioner must exercise caution during the medical certification of airmen. The variations in the concentration of melatonin can be effectively determined by radioimmunoassay, high-performance liquid chromatography, and gas chromatography-mass spectroscopy analytical techniques. These techniques are capable of measuring the human daytime (10 pg/mL) and nighttime (30-120 pg/mL) melatonin in plasma/serum. Melatonin measurements in victims of accidental death may allow forensic scientists and accident investigators to use the relationship between its concentration and the time of day when death occurred. The most accurate estimations of the time of death result from analysis of melatonin content of the whole pineal body, whereas less accurate estimates are obtained from serum and urine analyses. Pineal levels of melatonin are unlikely to be altered by exogenous melatonin, but its blood and urine levels would change. High blood levels in a daytime crash victim would suggest exogenous supplementation. The possible interfering effects of postmortem biochemical processes on melatonin concentrations in whole blood and in other tissues are not well understood, and there is a need for the continuing research into melatonin's chronobiological properties to define its proper applications and limitations. The indiscriminate use of melatonin by aviation professionals may pose unacceptable safety risks for air travel.

Melatonin: a "Higgs boson" in human reproduction.

PubMed

Dragojevic Dikic, Svetlana; Jovanovic, Ana Mitrovic; Dikic, Srdjan; Jovanovic, Tomislav; Jurisic, Aleksandar; Dobrosavljevic, Aleksandar

2015-02-01

As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones.

Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

ClinicalTrials.gov

2013-01-15

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

Extragonadal Germ Cell Tumors—Patient Version

Cancer.gov

Extragonadal germ cell tumors form in parts of the body outside the gonads. They may begin to grow anywhere in the body, but usually form in the pineal gland in the brain, the chest, the lower part of the spine, or the abdomen. Start here to find information on extragonadal germ cell tumors treatment.

Daily chronomics of proteomic profile in aging and rotenone-induced Parkinson's disease model in male Wistar rat and its modulation by melatonin.

PubMed

Jagota, Anita; Mattam, Ushodaya

2017-08-01

Aging is associated with changes in several basic parameters of circadian timing system (CTS) in mammals leading to circadian dysfunction. We had reported earlier that upon aging and in rotenone induced Parkinson's disease (RIPD) rat model there were significant alterations in the core clock genes expression levels and daily pulses. To identify biomarkers of aging and PD chronomics of proteomic day-night profiles in suprachiasmatic nucleus (SCN), pineal and substantia nigra (SN) in 3 month (m), 12, 24 m and RIPD rat model were studied at two time points i.e. Zeitgeber Time (ZT)-6 (mid-day) and ZT-18 (mid-night). Proteome analysis was done by using two dimensional (2-D) electrophoresis and the spots showing robust day-night variations were identified by using MALDI TOF/TOF analysis. In 3 m rats the number of proteins showing day-night variations were relatively more than 12, 24 m and RIPD rat model in SCN and SN. But in pineal there was increase in number of protein spots showing day-night variations in 24 m. Mass spectroscopy of the protein spots showing robust day night variation in aging and RIPD rats were identified. As melatonin, a multitasking molecule, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging, the effects of melatonin administration on differential alterations in chronomics of 2-D protein profiles in aging and RIPD male Wistar rats were studied. We report here that the melatonin could be playing an important role in modulating the chronomics of 2-D protein profiles. Additionally, various proteins were identified for the first time in this study showing significant day night variation in SCN, pineal and SN may prove useful towards targeting novel treatments for circadian dysfunction, good health and longevity.

Synchrotron microtomography of a Nothosaurus marchicus skull informs on nothosaurian physiology and neurosensory adaptations in early Sauropterygia

PubMed Central

Reich, Tobias; Araújo, Ricardo; Scheyer, Torsten M.

2018-01-01

Nothosaurs form a subclade of the secondarily marine Sauropterygia that was well represented in late Early to early Late Triassic marine ecosystems. Here we present and discuss the internal skull anatomy of the small piscivorous nothosaur Nothosaurus marchicus from coastal to shallow marine Lower Muschelkalk deposits (Anisian) of Winterswijk, The Netherlands, which represents the oldest sauropterygian endocast visualized to date. The cranial endocast is only partially encapsulated by ossified braincase elements. Cranial flattening and lateral constriction by hypertrophied temporal musculature grant the brain a straight, tubular geometry that lacks particularly well-developed cerebral lobes but does potentially involve distinguishable optic lobes, suggesting vision may have represented an important sense during life. Despite large orbit size, the circuitous muscular pathway linking the basisphenoidal and orbital regions indicates poor oculomotor performance. This suggests a rather fixed ocular orientation, although eye placement and neck manoeuvrability could have enabled binocular if not stereoscopic vision. The proportionally large dorsal projection of the braincase endocast towards the well-developed pineal foramen advocates substantial dependence on the corresponding pineal system in vivo. Structures corroborating keen olfactory or acoustic senses were not identified. The likely atrophied vomeronasal organ argues against the presence of a forked tongue in Nothosaurus, and the relative positioning of external and internal nares contrasts respiratory configurations proposed for pistosauroid sauropterygians. The antorbital domain furthermore accommodates a putative rostral sensory plexus and pronounced lateral nasal glands that were likely exapted as salt glands. Previously proposed nothosaurian ‘foramina eustachii’ arose from architectural constraints on braincase development rather than representing functional foramina. Several modifications to brain shape and accessory organs were achieved through heterochronic development of the cranium, particularly the braincase. In summary, the cranium of Nothosaurus marchicus reflects important physiological and neurosensory adaptations that enabled the group’s explosive invasion of shallow marine habitats in the late Early Triassic. PMID:29298295

Synchrotron microtomography of a Nothosaurus marchicus skull informs on nothosaurian physiology and neurosensory adaptations in early Sauropterygia.

PubMed

Voeten, Dennis F A E; Reich, Tobias; Araújo, Ricardo; Scheyer, Torsten M

2018-01-01

Nothosaurs form a subclade of the secondarily marine Sauropterygia that was well represented in late Early to early Late Triassic marine ecosystems. Here we present and discuss the internal skull anatomy of the small piscivorous nothosaur Nothosaurus marchicus from coastal to shallow marine Lower Muschelkalk deposits (Anisian) of Winterswijk, The Netherlands, which represents the oldest sauropterygian endocast visualized to date. The cranial endocast is only partially encapsulated by ossified braincase elements. Cranial flattening and lateral constriction by hypertrophied temporal musculature grant the brain a straight, tubular geometry that lacks particularly well-developed cerebral lobes but does potentially involve distinguishable optic lobes, suggesting vision may have represented an important sense during life. Despite large orbit size, the circuitous muscular pathway linking the basisphenoidal and orbital regions indicates poor oculomotor performance. This suggests a rather fixed ocular orientation, although eye placement and neck manoeuvrability could have enabled binocular if not stereoscopic vision. The proportionally large dorsal projection of the braincase endocast towards the well-developed pineal foramen advocates substantial dependence on the corresponding pineal system in vivo. Structures corroborating keen olfactory or acoustic senses were not identified. The likely atrophied vomeronasal organ argues against the presence of a forked tongue in Nothosaurus, and the relative positioning of external and internal nares contrasts respiratory configurations proposed for pistosauroid sauropterygians. The antorbital domain furthermore accommodates a putative rostral sensory plexus and pronounced lateral nasal glands that were likely exapted as salt glands. Previously proposed nothosaurian 'foramina eustachii' arose from architectural constraints on braincase development rather than representing functional foramina. Several modifications to brain shape and accessory organs were achieved through heterochronic development of the cranium, particularly the braincase. In summary, the cranium of Nothosaurus marchicus reflects important physiological and neurosensory adaptations that enabled the group's explosive invasion of shallow marine habitats in the late Early Triassic.

Melatonin: a chemical photoperiodic signal with clinical significance in humans.

PubMed

Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

1998-03-01

Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

Effects of illumination on human nocturnal serum melatonin levels and performance

NASA Technical Reports Server (NTRS)

Dollins, A. B.; Lynch, H. J.; Wurtman, R. J.; Deng, M. H.; Lieberman, H. R.

1993-01-01

In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36) = 12.77, p < 0.001, in a dose-dependent manner. Performance on vigilance, reaction time, and other tasks deteriorated throughout the night, consistent with known circadian variations in these parameters, but independent of ambient light intensity and circulating melatonin levels.

Human melatonin in magnetic fields: Second study. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, C.; Cook, M.R.; Cohen, H.D.

1995-11-01

Melatonin (MLT) is a hormone secreted primarily at night by the pineal gland in the brain. A number of studies suggest it is part of the body`s natural defenses against cancer. This hormone is reported to stimulate immune function and has been implicated in the control of cell proliferation, the growth of transplanted tumors, and the promotion and/or co-promotion of mammary tumors. MLT also plays a key role in the regulation of reproductive hormones implicated in a number of carcinogenic processes. Studies with rodents, although not always consistent, suggest that nocturnal MLT levels may be suppressed by electric or magneticmore » field (EMF) exposure. This relationship has been proposed as a possible biological mechanism to account for epidemiological reports linking chronic EMF exposure and increased cancer risk. Research was needed to determine if a similar suppression of MLT occurs when humans are exposed to magnetic fields at night.« less

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

NASA Astrophysics Data System (ADS)

Benoit, Julien; Abdala, Fernando; Van den Brandt, Marc J.; Manger, Paul R.; Rubidge, Bruce S.

2015-12-01

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.

Influence of Photoperiod on Hormones, Behavior, and Immune Function

PubMed Central

Walton, James C.; Weil, Zachary M.; Nelson, Randy J.

2011-01-01

Photoperiodism is the ability of plants and animals to measure environmental day length to ascertain time of year. Central to the evolution of photoperiodism in animals is the adaptive distribution of energetically challenging activities across the year to optimize reproductive fitness while balancing the energetic tradeoffs necessary for seasonally- appropriate survival strategies. The ability to accurately predict future events requires endogenous mechanisms to permit physiological anticipation of annual conditions. Day length provides a virtually noise free environmental signal to monitor and accurately predict time of the year. In mammals, melatonin provides the hormonal signal transducing day length. Duration of pineal melatonin is inversely related to day length and its secretion drives enduring changes in many physiological systems, including the HPA, HPG, and brain-gut axes, the autonomic nervous system, and the immune system. Thus, melatonin is the fulcrum mediating redistribution of energetic investment among physiological processes to maximize fitness and survival. PMID:21156187

Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

PubMed Central

Suidan, Georgette L.; Vanderhorst, Veronique; Hampton, Thomas G.; Wong, Siu Ling; Voorhees, Jaymie R.; Wagner, Denisa D.

2013-01-01

The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (−/−) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system. PMID:23516593

Lack of tryptophan hydroxylase-1 in mice results in gait abnormalities.

PubMed

Suidan, Georgette L; Duerschmied, Daniel; Dillon, Gregory M; Vanderhorst, Veronique; Hampton, Thomas G; Wong, Siu Ling; Voorhees, Jaymie R; Wagner, Denisa D

2013-01-01

The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (-/-) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system.

It's time to swim! Zebrafish and the circadian clock.

PubMed

Vatine, Gad; Vallone, Daniela; Gothilf, Yoav; Foulkes, Nicholas S

2011-05-20

The zebrafish represents a fascinating model for studying key aspects of the vertebrate circadian timing system. Easy access to early embryonic development has made this species ideal for investigating how the clock is first established during embryogenesis. In particular, the molecular basis for the functional development of the zebrafish pineal gland has received much attention. In addition to this dedicated clock and photoreceptor organ, and unlike the situation in mammals, the clocks in zebrafish peripheral tissues and even cell lines are entrainable by direct exposure to light thus providing unique insight into the function and evolution of the light input pathway. Finally, the small size, low maintenance costs and high fecundity of this fish together with the availability of genetic tools make this an attractive model for forward genetic analysis of the circadian clock. Here, we review the work that has established the zebrafish as a valuable clock model organism and highlight the key questions that will shape the future direction of research. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Melatonin and human mitochondrial diseases

PubMed Central

Sharafati-Chaleshtori, Reza; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud; Soltani, Amin

2017-01-01

Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function. PMID:28400824

What is known about melatonin, chemotherapy and altered gene expression in breast cancer

PubMed Central

Martínez-Campa, Carlos; Menéndez-Menéndez, Javier; Alonso-González, Carolina; González, Alicia; Álvarez-García, Virginia; Cos, Samuel

2017-01-01

Melatonin, synthesized in and released from the pineal gland, has been demonstrated by multiple in vivo and in vitro studies to have an oncostatic role in hormone-dependent tumors. Furthermore, several clinical trials point to melatonin as a promising adjuvant molecule to be considered for cancer treatment. In the past few years, evidence of a broader spectrum of action of melatonin as an antitumor agent has arisen; thus, melatonin appears to also have therapeutic effects in several types of hormone-independent cancer, including ovarian, leukemic, pancreatic, gastric and non-small cell lung carcinoma. In the present study, the latest findings regarding melatonin molecular actions when concomitantly administered with either radiotherapy or chemotherapy in cancer were reviewed, with a particular focus on hormone-dependent breast cancer. Finally, the present study discusses which direction should be followed in the next years to definitely clarify whether or not melatonin administration could protect against non-desirable effects (such as altered gene expression and post-translational protein modifications) caused by chemotherapy or radiotherapy treatments. As treatments move towards personalized medicine, comparative gene expression profiling with and without melatonin may be a powerful tool to better understand the antitumor effects of melatonin, the pineal gland hormone. PMID:28454355

[Circannual rhythms of bone marrow cell composition in animals during aging: the role of pineal factors].

PubMed

Labunets', I F

2007-01-01

It was investigated the influence of pineal gland's peptides (epithalamin, epithalon) and indols (melatonin) on the aging changes of circannual rhythms of stromal cells-precurcors (CFC-F), granulocyte-macrophage cells-precurcors (CFC-GM), CD4+, Mac-1+ and CD19+-cells amount in bone marrow of mice CBA. In old animals the rhythmical disturbances of the indices were characterized by loss of fluctuations (Mac 1+-cells), increase of CD4+-cells amplitude, displacement of seasonal acrophase (CFC-F), inversion of rhythm (CFC-GM), desynchronization. In old mice after epithalamin injections the season differences between the amount of Mac-1+-cells restored, CD4+-cells amplitude diminished, the amount of CFC-GM increased in spring and CFC-F diminished in autumn. The influence of epithalon on CFC-F and CFG-GM rhythm was in a smaller dose. The rhythms of some indices in old animals showed a pattern observed in adults. After melatonin injections to adult mice in winter the amount of CD4+-cells increased; the ratio CFC-GM and CFC-F changed because of increase of stromal fibroblasts. In old mice the indices were without changes.

Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice.

PubMed

Kossoy, George; Anisimov, Vladimir N; Ben-Hur, Herzel; Kossoy, Nadja; Zusman, Itshak

2006-01-01

The potential preventive effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on spontaneous tumorigenesis in mice was studied. One-year-old female C3H/He mice were kept for 6.5 months under standard conditions. Epitalon was injected at a dose of 0.1 microg, 5 times a week. Long-term exposure to Epitalon in small doses did not show any toxic effect. Treatment with Epitalon decreased the number of tumor-bearing mice with malignant tumors and prevented the development of metastases. Spontaneous tumors of the reproductive organs (mammary glands and ovaries) were predominant in both groups of mice (control and experimental). The mammary gland tumors were different variants of invasive ductal carcinomas. In the ovaries, granulosa-cell tumors were found. Tumors were in the minority in other organs and had benign characteristics. In control mice, metastases were found in 3 out of 9 tumor-bearing mice, all of them being from tumors of the reproductive organs. Treatment with Epitalon slowed down the development of metastases from spontaneous tumors, and no metastases were found in the experimental mice. These data highlight the antimetastatic effect of Epitalon as part of its oncostatic properties.

[THE CHANGES OF THE INTERRELATIONS OF THE PINEAL GLAND AND THE ORGANS OF THE IMMUNE SYSTEM IN RATS IN RESPONSE TO MELATONIN ADMINISTRATION IN LIGHT REGIME DISTURBANCES].

PubMed

Litvinenko, G I; Gritzyk, O B; Mel'nikova, Ye V; Avrorov, P A; Tenditnik, M V; Shurlygina, A V; Trufakin, V A

2015-01-01

In this work the correlation analysis was applied to detect the integrated response of the pineal gland (PG) and immunocompetent organs of male Wistar rats in response to administration of melatonin (MT) in light regime disturbances. Animals were kept for 14 days under natural or continuous light (CL). Then for 7 days they received the injections of either 0.9% solution of sodium chloride or MT, after which the rats were decapitated and the mass of their body, PG, thymus and spleen was determined. The lymphocyte subpopulations of the thymus and spleen were studied by flow cytometry. The amount of lipofuscin in PG was assessed by the intensity of autofluorescence in organ frozen sections in 560-600 nm wavelength range. It was found that under the influence of MT, the number of intraorgan correlations in the immune system increased, regardless of the light regime. In animals on CL treated with MT, the number of interorgan connections was reduced, while negative correlations appeared between PG lipofuscin content and cellular composition of the spleen. The synchronizing and adaptogenic effects of MT were most pronounced under conditions of CL.

Delayed effect of pinealectomy on hibernation of the golden-mantled ground squirrel

NASA Astrophysics Data System (ADS)

Ralph, C. L.; Harlow, H. J.; Phillips, J. A.

1982-12-01

Pinealectomy or radical sham pinealectomy were performed on adult golden-mantled ground squirrels, Spermophilus (=Citellus) lateralis, approximately 1 month prior to the date of normal winter emergence. The first hibernatory period and subsequent active season were not different in either of the operated groups from intact animals. However, although the initiation of the second hibernatory period was not affected in the pinealectomized animals, this group failed to show the progressive increase in the length of heterothermic bouts that is characteristic of normal hibernation. Also, terminal arousal occurred approximately 6 weeks earlier in the second year after pinealectomy. Male squirrels showed a corresponding time compression in their annual gonadal cycle, as was assessed by testicular state. These results suggest that the pineal gland of the golden-mantled ground squirrel is involved in the expression of the annual hibernatory cycle. In the absence of the pineal gland the adult of this species is unable to sustain the normal depth and duration of hibernation in the second over-wintering period following pinealectomy. We have carried out additional experiments with young, laboratory-born S. lateralis and with field-caught, adult S. richardsonii. The results of these studies also are described in this paper.

Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 1 -- Background and purpose, methods, results, discussion. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaune, W.; Davis, S.; Stevens, R.

Scientists have postulated a link between exposure to magnetic fields and reduced blood melatonin levels. This EPRI study was designed to supplement a National Cancer Institute study (NCI-BC) of magnetic fields, light-at-night, and the risk of breast cancer. By expanding the exposure assessment of the NCI-BC and collecting data on urine melatonin levels, this project provides new insight into a possible magnetic field-melatonin link. It has been proposed that exposure to 60-Hz (power frequency) magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in melatonin production in the pineal gland. It remains unknown whethermore » the human pineal gland is reproducibly responsive or sensitive to magnetic field exposure, and whether such exposures could alter elements of the endogenous hormonal environment in women that might be important in the etiology of breast cancer. The objective of this research was to investigate whether exposure to power-frequency magnetic fields and/or light-at-night is associated with levels of the primary urinary melatonin metabolite in women without a history of breast cancer.« less

Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 2 -- Magnetic field exposure analysis. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaune, W.; Davis, S.; Stevens, R.

Scientists have postulated a link between exposure to magnetic fields and reduced blood melatonin levels. This EPRI study was designed to supplement a National Cancer Institute study (NCI-BC) of magnetic fields, light-at-night, and the risk of breast cancer. By expanding the exposure assessment of the NCI-BC and collecting data on urine melatonin levels, this project provides new insight into a possible magnetic field-melatonin link. It has been proposed that exposure to 60-Hz (power frequency) magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in melatonin production in the pineal gland. It remains unknown whethermore » the human pineal gland is reproducibly responsive or sensitive to magnetic field exposure, and whether such exposures could alter elements of the endogenous hormonal environment in women that might be important in the etiology of breast cancer. The objective of this research was to investigate whether exposure to power-frequency magnetic fields and/or light-at-night is associated with levels of the primary urinary melatonin metabolite in women without a history of breast cancer.« less

Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders.

PubMed

Pagan, Cécile; Goubran-Botros, Hany; Delorme, Richard; Benabou, Marion; Lemière, Nathalie; Murray, Kerren; Amsellem, Frédérique; Callebert, Jacques; Chaste, Pauline; Jamain, Stéphane; Fauchereau, Fabien; Huguet, Guillaume; Maronde, Erik; Leboyer, Marion; Launay, Jean-Marie; Bourgeron, Thomas

2017-05-18

Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as very frequent features in individuals with ASD. To address the mechanisms of these dysfunctions, we investigated melatonin synthesis in post-mortem pineal glands - the main source of melatonin (9 patients and 22 controls) - and gut samples - the main source of serotonin (11 patients and 13 controls), and in blood platelets from 239 individuals with ASD, their first-degree relatives and 278 controls. Our results elucidate the enzymatic mechanism for melatonin deficit in ASD, involving a reduction of both enzyme activities contributing to melatonin synthesis (AANAT and ASMT), observed in the pineal gland as well as in gut and platelets of patients. Further investigations suggest new, post-translational (reduced levels of 14-3-3 proteins which regulate AANAT and ASMT activities) and post-transcriptional (increased levels of miR-451, targeting 14-3-3ζ) mechanisms to these impairments. This study thus gives insights into the pathophysiological pathways involved in ASD.

Influence of light/dark, seasonal and lunar cycles on the nuclear size of the pinealocytes of the rat.

PubMed

Martínez-Soriano, F; Armañanzas, E; Ruiz-Torner, A; Valverde-Navarro, A A

2002-01-01

Morphological and physiological studies suggest a possible division of the pineal parenchyma into an external or "cortical" and another central or "medullar" layer. We have studied the possible influence of the light/dark, seasonal and lunar cycles on the nuclear size of the pinealocytes of the rat in both the hypothetical "cortical" and "medullar" layers. Forty male Wistar rats were used. Experiment was carried out in two seasons, winter and spring, two lunar phases, full moon and new moon, and the two circadian phases, photophase and scotophase. The nuclear volume of the pinealocytes, calculated from the Jacobj's formula, was the karyometric parameter used as measurement of the nuclear size. Main results showed that nuclear volume of the cortical pinealocytes was greater than that of the medullar pinealocytes only during the photophases of winter new-moon days and spring full moon days, whereas in all the remaining situations, the greater nuclear sizes were found in the pinealocytes of the medullar layer. These results support the existence of independent morphological variations of the pinealocyte in the central and peripheral zones of the pineal gland.

Effects of 60 Hz Magnetic Field Exposure on the Pineal and Hypothalamic-Pituitary-Gonadal Axis in the Siberian Hamster (Phodopus Sungorus)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Bary W.; Matt, Kathleen S.; Morris, James E.

Experiments using the dwarf Siberian hamster Phodopus sungorus were carried out to determine possible neuroendocrine consequences of one-time and repeated exposures to 60 Hz magnetic fields (MF). Animals were maintained in either a short-light (SL, 8 h light:16 h dar) or long-light (LL, 16 h light:8h dark) photoperiod.

Fluorine F 18 Fluorodopa-Labeled PET Scan in Planning Surgery and Radiation Therapy in Treating Patients With Newly Diagnosed High- or Low-Grade Malignant Glioma

ClinicalTrials.gov

2018-04-30

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma

Craniospinal Irradiation for Trilateral Retinoblastoma Following Ocular Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, Lawrence B.; Bentel, Gunilla; Sherouse, George W.

A case study is presented. Craniospinal radiotherapy and a three-field pineal boost for trilateral retinoblastoma were delivered to a patient previously irradiated for ocular retinoblastoma. The availability of CT-based three-dimensional treatment planning provided the capability of identifying the previously irradiated volume as a three-dimensional anatomic structure and of designing a highly customized set of treatment beams that minimized reirradiation of that volume.

The effects of light on man and other mammals

NASA Technical Reports Server (NTRS)

Wurtman, R. J.

1975-01-01

The present article describes the best-studied extravisual effects of visible and ultraviolet light on humans and other mammals. It also considers the possible biological consequences to man of living in artificially lighted environments that differ significantly from the milieu in which he evolved. Cumulative evidence favors the beneficial influences of sunlight: vitamin D activation, plasma bilirubin elimination, inhibition of pineal melatonin synthesis, etc.

Disruption of adolescents' circadian clock: The vicious circle of media use, exposure to light at night, sleep loss and risk behaviors.

PubMed

Touitou, Yvan; Touitou, David; Reinberg, Alain

2016-11-01

Although sleep is a key element in adolescent development, teens are spending increasing amounts of time online with health risks related to excessive use of electronic media (computers, smartphones, tablets, consoles…) negatively associated with daytime functioning and sleep outcomes. Adolescent sleep becomes irregular, shortened and delayed in relation with later sleep onset and early waking time due to early school starting times on weekdays which results in rhythm desynchronization and sleep loss. In addition, exposure of adolescents to the numerous electronic devices prior to bedtime has become a great concern because LEDs emit much more blue light than white incandescent bulbs and compact fluorescent bulbs and have therefore a greater impact on the biological clock. A large number of adolescents move to evening chronotype and experience a misalignment between biological and social rhythms which, added to sleep loss, results in e.g. fatigue, daytime sleepiness, behavioral problems and poor academic achievement. This paper on adolescent circadian disruption will review the sensitivity of adolescents to light including LEDs with the effects on the circadian system, the crosstalk between the clock and the pineal gland, the role of melatonin, and the behavior of some adolescents(media use, alcohol consumption, binge drinking, smoking habits, stimulant use…). Lastly, some practical recommendations and perspectives are put forward. The permanent social jet lag resulting in clock misalignment experienced by a number of adolescents should be considered as a matter of public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondrial bioenergetics decay in aging: beneficial effect of melatonin.

PubMed

Paradies, Giuseppe; Paradies, Valeria; Ruggiero, Francesca M; Petrosillo, Giuseppe

2017-11-01

Aging is a biological process characterized by progressive decline in physiological functions, increased oxidative stress, reduced capacity to respond to stresses, and increased risk of contracting age-associated disorders. Mitochondria are referred to as the powerhouse of the cell through their role in the oxidative phosphorylation to generate ATP. These organelles contribute to the aging process, mainly through impairment of electron transport chain activity, opening of the mitochondrial permeability transition pore and increased oxidative stress. These events lead to damage to proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid of the inner mitochondrial membrane, plays a pivotal role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis and in mitochondrial membrane stability and dynamics. Cardiolipin alterations are associated with mitochondrial bienergetics decline in multiple tissues in a variety of physiopathological conditions, as well as in the aging process. Melatonin, the major product of the pineal gland, is considered an effective protector of mitochondrial bioenergetic function. Melatonin preserves mitochondrial function by preventing cardiolipin oxidation and this may explain, at least in part, the protective role of this compound in mitochondrial physiopathology and aging. Here, mechanisms through which melatonin exerts its protective role against mitochondrial dysfunction associated with aging and age-associated disorders are discussed.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

PubMed

Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-03-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

PubMed Central

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain. PMID:23434588

Therapeutic perspectives for melatonin agonists and antagonists.

PubMed

Delagrange, P; Atkinson, J; Boutin, J A; Casteilla, L; Lesieur, D; Misslin, R; Pellissier, S; Pénicaud, L; Renard, P

2003-04-01

Melatonin is a neurohormone synthesized in the pineal gland during the dark period in all species, including humans. The diversity and differences in melatonin receptor distribution in the brain and extracerebral organs suggest multiple functional roles for melatonin. Administration of melatonin agonists reduces neophobia and treatment with a melatonin antagonist during the dark period reverses the anxiolytic-like effect of endogenous melatonin. Chronic treatment with agonists prevents various perturbations induced by chronic mild stress. Melatonin in vivo directly constricts cerebral arterioles in rats and decreases the lower limit of cerebral blood flow autoregulation, suggesting that melatonin may diminish the risk of hypoperfusion-induced cerebral ischemia. At the extracerebral level, melatonin regulates intestinal motility in rats. The intestinal postprandial motor response is shorter in the dark phase than in the light phase and this reduction is reversed in animals pretreated with a melatonin antagonist. Moreover, melatonin reduces the duration of cholecystokinin excitomotor effect. Endogenous melatonin may modulate intestinal motility to coordinate intestinal functions such as digestion and transit and control the metabolism of the animal. An adipocyte melatonin binding site may also participate in this control. Melatonin is involved in a wide range of physiological functions. The question remains as to whether evolution, adaptation and diurnal life have modified the physiological role of melatonin in humans. Moreover, the functional role of each of the receptor subtypes has to be characterized to design selective ligands to treat specific diseases.

Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

ClinicalTrials.gov

2015-06-03

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Ependymoblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Grade III Meningioma; Meningeal Hemangiopericytoma; Mixed Glioma; Pineal Gland Astrocytoma; Brain Tumor

Yoga Therapy in Treating Patients With Malignant Brain Tumors

ClinicalTrials.gov

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

A Descriptive Study of a Perioperative Pain Service Program

DTIC Science & Technology

1999-10-01

the Renaissance. Leading the forefront was Renee Descartes , a French mathematician. He described nerves as hollow tubes through which fine threads...Sensations had to interact with the mind or soul, which Descartes considered to be separate from the body and unaffected by external and mechanical...forces. Integration of the mind and body, according to Descartes , occurred within the pineal gland. Pain, therefore, was a Co-axial Narcotics 17 state

A Descriptive Study of a Perioperative Pain Service Program

DTIC Science & Technology

1999-07-28

to the sense of pain (Jaros, 1991) . Reason and analytic deduction blossomed during the Renaissance. Leading the forefront was Renee Descartes , a... Descartes considered to be separate from the body and unaffected by external and mechanical forces. Integration of the mind and body, according to... Descartes , occurred within the pineal gland. Pain, therefore, was a Co-axial Narcotics 17 state of excessive sensory awareness modulated by the mind

Age and seasonal differences in the synthesis and metabolism of testosterone by testicular tissue and pineal HIOMT activity of Uinta ground squirrels (Spermophilus armatus)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellis, L.C.; Balph, D.F.

Male Uinta ground squirrels (Spermophilus armatus) were sacrificed from a free-living population during the breeding season, which immediately followed emergence from hibernation; after the reproductive season; and just prior to aestivation/hibernation. HIOMT activity of the pineal gland was assayed and related to the ability of the gonads to synthesize and metabolize testosterone. Older squirrels had higher HIOMT activity than did the younger animals. The activity of this enzyme was lowest in squirrels during the breeding season. HIOMT activity increased after the breeding season to its highest level just before the squirrels enter aestivation/hibernation. At this time, testicular weight increased concomitantmore » with an apparent increase in HIOMT activity. Testicular size and weight were largest at the time of emergence of the animals from hibernation. Androgen synthesis was also greatest during the breeding season. As would be expected, both decreased rapidly thereafter. The testes formed little 17..cap alpha..,20..cap alpha..-dihydroxyprogesterone during or after the breeding season, contrary to what has been reported for rats and house sparrows. The older squirrels demonstrated a greater capacity for testosterone metabolism during the breeding season than did the younger animals.« less

SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors

ClinicalTrials.gov

2018-04-09

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Ganglioglioma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Pleomorphic Xanthoastrocytoma, Anaplastic; Atypical Teratoid/Rhabdoid Tumor; Brain Cancer; Brain Tumor; Central Nervous System Neoplasms; Choroid Plexus Carcinoma; CNS Embryonal Tumor With Rhabdoid Features; Ganglioneuroblastoma of Central Nervous System; CNS Tumor; Embryonal Tumor of CNS; Ependymoma; Glioblastoma; Glioma; Glioma, Malignant; Medulloblastoma; Medulloblastoma; Unspecified Site; Medulloepithelioma; Neuroepithelial Tumor; Neoplasms; Neoplasms, Neuroepithelial; Papillary Tumor of the Pineal Region (High-grade Only); Pediatric Brain Tumor; Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only); Pineoblastoma; Primitive Neuroectodermal Tumor; Recurrent Medulloblastoma; Refractory Brain Tumor; Neuroblastoma. CNS; Glioblastoma, IDH-mutant; Glioblastoma, IDH-wildtype; Medulloblastoma, Group 3; Medulloblastoma, Group 4; Glioma, High Grade; Neuroepithelial Tumor, High Grade; Medulloblastoma, SHH-activated and TP53 Mutant; Medulloblastoma, SHH-activated and TP53 Wildtype; Medulloblastoma, Chromosome 9q Loss; Medulloblastoma, Non-WNT Non-SHH, NOS; Medulloblastoma, Non-WNT/Non-SHH; Medulloblastoma, PTCH1 Mutation; Medulloblastoma, WNT-activated; Ependymoma, Recurrent; Glioma, Recurrent High Grade; Glioma, Recurrent Malignant; Embryonal Tumor, NOS; Glioma, Diffuse Midline, H3K27M-mutant; Embryonal Tumor With Multilayered Rosettes (ETMR); Ependymoma, NOS, WHO Grade III; Ependymoma, NOS, WHO Grade II; Medulloblastoma, G3/G4; Ependymoma, RELA Fusion Positive

Melatoninergic System in Parkinson's Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms

PubMed Central

Schamne, Marissa Giovanna; Sampaio, Tuane Bazanella; Pértile, Renata Aparecida Nedel; Fernandes, Pedro Augusto Carlos Magno; Markus, Regina P.

2016-01-01

Melatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulates the expression of neurotrophins that are involved in the survival of dopaminergic neurons and reduces α-synuclein aggregation, thus protecting the dopaminergic system against damage. The unbalance of pineal melatonin synthesis can predispose the organism to inflammatory and neurodegenerative diseases such as Parkinson's disease (PD). The aim of this review is to summarize the knowledge about the potential role of the melatoninergic system in the pathogenesis and treatment of PD. The literature reviewed here indicates that PD is associated with impaired brain expression of melatonin and its receptors MT1 and MT2. Exogenous melatonin treatment presented an outstanding neuroprotective effect in animal models of PD induced by different toxins, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat, and maneb. Despite the neuroprotective effects and the improvement of motor impairments, melatonin also presents the potential to improve nonmotor symptoms commonly experienced by PD patients such as sleep and anxiety disorders, depression, and memory dysfunction. PMID:27829983

Endoscopic selective sampling of human ventricular CSF: a new perspective.

PubMed

Longatti, P; Perin, A; Rizzo, V; Comai, S; Bertazzo, A; Allegri, G

2004-12-01

Neuroendoscopy has achieved extensive acceptance among neurosurgeons as a minimally invasive technique for the treatment of patients affected by blocked hydrocephalus. During endoscopic procedures minimal CSF amounts from selected anatomic sites of the ventricles can be withdrawn. Steerable endoscopes are used and their flexibility facilitates the aspiration of CSF during the preliminary inspection through the ventricular cavities, without any interference with the surgical actions or additional risks for the patients. In this preliminary study the concentrations of melatonin and other related metabolites in the lateral ventricles, third ventricle, pineal recess and infundibular recess were examined. The data obtained from a patient affected by blocked hydrocephalus confirmed a constant and significant difference of concentration of these substances, for instance, melatonin levels were found to be much higher in the third ventricle (542 pg/mL in its centre) than in the lateral ventricle (172 pg/mL in the right ventricle). Nevertheless, instead of what we would expect, the highest melatonin concentrations were not found in the pineal recess (438 pg/mL). In the future, neuroendoscopy, beside its evident therapeutic efficacy, could open new perspectives in the study of both CSF biochemistry and physiology, allowing a highly selective approach to the various substances which are released and float in it.

Early development of circadian rhythmicity in the suprachiamatic nuclei and pineal gland of teleost, flounder (Paralichthys olivaeus), embryos.

PubMed

Mogi, Makoto; Uji, Susumu; Yokoi, Hayato; Suzuki, Tohru

2015-08-01

Circadian rhythms enable organisms to coordinate multiple physiological processes and behaviors with the earth's rotation. In mammals, the suprachiasmatic nuclei (SCN), the sole master circadian pacemaker, has entrainment mechanisms that set the circadian rhythm to a 24-h cycle with photic signals from retina. In contrast, the zebrafish SCN is not a circadian pacemaker, instead the pineal gland (PG) houses the major circadian oscillator. The SCN of flounder larvae, unlike that of zebrafish, however, expresses per2 with a rhythmicity of daytime/ON and nighttime/OFF. Here, we examined whether the rhythm of per2 expression in the flounder SCN represents the molecular clock. We also examined early development of the circadian rhythmicity in the SCN and PG. Our three major findings were as follows. First, rhythmic per2 expression in the SCN was maintained under 24 h dark (DD) conditions, indicating that a molecular clock exists in the flounder SCN. Second, onset of circadian rhythmicity in the SCN preceded that in the PG. Third, both 24 h light (LL) and DD conditions deeply affected the development of circadian rhythmicity in the SCN and PG. This is the first report dealing with the early development of circadian rhythmicity in the SCN in fish. © 2015 Japanese Society of Developmental Biologists.

Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus-Consequences to Melatonin Dysfunction.

PubMed

Hardeland, Rüdiger

2013-03-12

The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases.

Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.

PubMed

Blask, David E; Dauchy, Robert T; Dauchy, Erin M; Mao, Lulu; Hill, Steven M; Greene, Michael W; Belancio, Victoria P; Sauer, Leonard A; Davidson, Leslie

2014-01-01

The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder.

PubMed

Tordjman, Sylvie; Anderson, George M; Pichard, Nadège; Charbuy, Henriette; Touitou, Yvan

2005-01-15

Many studies in autistic disorder report sleep problems and altered circadian rhythms, suggesting abnormalities in melatonin physiology. Additionally, melatonin, a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. Nocturnal urinary excretion of 6-sulphatoxymelatonin was measured by radioimmunoassay in groups of children and adolescents with autistic disorder (n = 49) and normal control individuals (n = 88) matched on age, sex, and Tanner stage of puberty. Nocturnal 6-sulphatoxymelatonin excretion rate was significantly and substantially lower in patients with autism than in normal controls (mean +/- SEM, .75 +/- .11 vs. 1.80 +/- .17 microg/hr, p =.0001), and was significantly negatively correlated with severity of autistic impairments in verbal communication and play (p < .05). These findings indicate clearly that nocturnal production of melatonin is reduced in autism. Further research is warranted in order to understand the mechanisms underlying the lower melatonin production, to assess the impact of altered melatonin on the pathophysiology and behavioral expression of autistic disorder, and to determine the utility of melatonin administration in individuals with autism.

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

PubMed Central

Delagrange, Philippe; Krause, Diana N.; Sugden, David; Cardinali, Daniel P.; Olcese, James

2010-01-01

The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT1 and MT2, that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin's discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer. PMID:20605968

Thyroid Hormone and Seasonal Rhythmicity

PubMed Central

Dardente, Hugues; Hazlerigg, David G.; Ebling, Francis J. P.

2014-01-01

Living organisms show seasonality in a wide array of functions such as reproduction, fattening, hibernation, and migration. At temperate latitudes, changes in photoperiod maintain the alignment of annual rhythms with predictable changes in the environment. The appropriate physiological response to changing photoperiod in mammals requires retinal detection of light and pineal secretion of melatonin, but extraretinal detection of light occurs in birds. A common mechanism across all vertebrates is that these photoperiod-regulated systems alter hypothalamic thyroid hormone (TH) conversion. Here, we review the evidence that a circadian clock within the pars tuberalis of the adenohypophysis links photoperiod decoding to local changes of TH signaling within the medio-basal hypothalamus (MBH) through a conserved thyrotropin/deiodinase axis. We also focus on recent findings which indicate that, beyond the photoperiodic control of its conversion, TH might also be involved in longer-term timing processes of seasonal programs. Finally, we examine the potential implication of kisspeptin and RFRP3, two RF-amide peptides expressed within the MBH, in seasonal rhythmicity. PMID:24616714

Effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells.

PubMed

Shu, Tao; Wu, Tao; Pang, Mao; Liu, Chang; Wang, Xuan; Wang, Juan; Liu, Bin; Rong, Limin

2016-06-03

Melatonin, a lipophilic molecule mainly synthesized in the pineal gland, has properties of antioxidation, anti-inflammation, and antiapoptosis to improve neuroprotective functions. Here, we investigate effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells (iPSCs). iPSCs were induced into neural stem cells (NSCs), then further differentiated into neurons in medium with or without melatonin, melatonin receptor antagonist (Luzindole) or Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). Melatonin significantly promoted the number of neurospheres and cell viability. In addition, Melatonin markedly up-regulated gene and protein expression of Nestin and MAP2. However, Luzindole or LY294002 attenuated these increase. The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

Melatonin.

PubMed

Hardeland, Rüdiger; Pandi-Perumal, S R; Cardinali, Daniel P

2006-03-01

Melatonin, originally discovered as a hormone of the pineal gland, is produced by bacteria, protozoa, plants, fungi, invertebrates, and various extrapineal sites of vertebrates, including gut, skin, Harderian gland, and leukocytes. Biosynthetic pathways seem to be identical. Actions are pleiotropic, mediated by membrane and nuclear receptors, other binding sites or chemical interactions. Melatonin regulates the sleep/wake cycle, other circadian and seasonal rhythms, and acts as an immunostimulator and cytoprotective agent. Circulating melatonin is mostly 6-hydroxylated by hepatic P450 monooxygenases and excreted as 6-sulfatoxymelatonin. Pyrrole-ring cleavage is of higher importance in other tissues, especially the brain. The product, N1-acetyl-N2-formyl-5-methoxykynuramine, is formed by enzymatic, pseudoenzymatic, photocatalytic, and numerous free-radical reactions. Additional metabolites result from hydroxylation and nitrosation. The secondary metabolite, N1-acetyl-5-methoxykynuramine, supports mitochondrial function and downregulates cyclooxygenase 2. Antioxidative protection, safeguarding of mitochondrial electron flux, and in particular, neuroprotection, have been demonstrated in many experimental systems. Findings are encouraging to use melatonin as a sleep promoter and in preventing progression of neurodegenerative diseases.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

PubMed

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

The melatonin-sensitive circadian clock of the enteric bacterium Enterobacter aerogenes.

PubMed

Paulose, Jiffin K; Cassone, Vincent M

2016-09-02

Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26°C to 40°C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves.

Melatonin and male reproduction.

PubMed

Li, Chunjin; Zhou, Xu

2015-06-15

Melatonin is a neurohormone secreted by the pineal gland whose concentrations in the body are regulated by both the dark-light and seasonal cycles. The reproductive function of seasonal breeding animals is clearly influenced by the circadian variation in melatonin levels. Moreover, a growing body of evidence indicates that melatonin has important effects in the reproduction of some non-seasonal breeding animals. In males, melatonin affects reproductive regulation in three main ways. First, it regulates the secretion of two key neurohormones, GnRH and LH. Second, it regulates testosterone synthesis and testicular maturation. Third, as a potent free radical scavenger that is both lipophilic and hydrophilic, it prevents testicular damage caused by environmental toxins or inflammation. This review summarizes the existing data on the possible biological roles of melatonin in male reproduction. Overall, the literature data indicate that melatonin affects the secretion of both gonadotropins and testosterone while also improving sperm quality. This implies that it has important effects on the regulation of testicular development and male reproduction. Copyright © 2015. Published by Elsevier B.V.

A Technical Approach to Expedited Processing of NTPR Radiation Dose Assessments

DTIC Science & Technology

2011-10-01

Pharynx ET Region+ Surrogate Oral Cavity and Pharynx (140-149) None PNLGL Pineal Gland Brain Surrogate Other Endocrine Glands (194) PITTGL PITTGL...including brain); endocrine glands other than thyroid; other and ill-defined sites; lymphoma and multiple myeloma Risk depends on age at exposure...endocrine glands 14 45 Cancers of other and ill-defined sites 16 50 Lymphoma and multiple myeloma 22 61 Leukemia, excluding CLL 1.9 (5 years) 41

Geomagnetic field detection in rodents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olcese, J.; Reuss, S.; Semm, P.

1988-01-01

In addition to behavioral evidence for the detection of earth-strength magnetic fields (MF) by rodents, recent investigations have revealed that electrophysiological and biochemical responses to MF occur in the pineal organ and retina of rodents. In addition, ferrimagnetic deposits have been identified in the ethmoidal regions of the rodent skull. These findings point to a new sensory phenomenon, which interfaces with many fields of biology, including neuroscience, psychophysics, behavioral ecology, chronobiology and sensory physiology.

Evaluation of plasma levels of melatonin after midazolam or sodium thiopental anesthesia in children.

PubMed

Muñoz-Hoyos, Antonio; Heredia, Francisco; Moreno, Francisco; García, Joaquín José; Molina-Carballo, Antonio; Escames, Germaine; Acuña-Castroviejo, Darío

2002-05-01

Midazolam and sodium thiopental are two commonly used drugs in anesthesia for minor surgical procedures in children. A relationship exists between benzodiazepines (BNZ), barbiturates and melatonin. Whereas these drugs increase pineal melatonin production, the indoleamine amplifies the effects of both BNZ and barbiturates on the central nervous system (CNS). Our purpose was thus to analyze the plasma levels of melatonin before and during midazolam or sodium thiopental anesthesia in children subjected to ambulatory surgical procedures. Midazolam (0.4 mg/kg) or sodium thiopental (5 mg/kg) were administered i.v. to 33 and 32 children (aged between 2 and 14 yr), respectively, and blood samples were taken before and 5, 10 and 20 min after the drugs were administered. Melatonin was measured in plasma by a commercial radioimmunoassay kit previously standardized in our laboratory. The results showed that neither midazolam nor sodium thiopental anesthesia significantly affected the levels of melatonin studied at anytime. Significant correlations were found comparing the levels of melatonin between the different times studied. These results suggest that midazolam or sodium thiopental did not affect melatonin production by the pineal gland, thus avoiding a possible potentiating effect of the indoleamine on the central effects of these drugs during anesthesia. However, the possibility that changes in melatonin had been masked by the antioxidant role of the neurohormone are discussed.

Primary atypical teratoid/rhabdoid tumor of central nervous system in children: a clinicopathological analysis and review of literature in China.

PubMed

Yang, Min; Chen, Xi; Wang, Ning; Zhu, Kun; Hu, Ying-Zi; Zhao, Yun; Shu, Yan; Zhao, Man-Li; Gu, Wei-Zhong; Tang, Hong-Feng

2014-01-01

Atypical teratoid/rhabdoid tumor (AT/RT) is a very rare and highly malignant embryonal tumor in the central nervous system (CNS). Five patients (4 girls and 1 boy) with AT/RT were treated in our hospital. The clinical histories, symptoms, neuroimaging aspects, therapies, histological and immunohistochemical findings and follow-up information were reviewed. The patients ranged from 8 to 40 months with a mean age of 20.6 months. One tumor was located in the spinal cord, two in cerebellum and two in the pineal region. The imagings of the tumors resemble medulloblastomas. Pathological examinations showed that one patient had medulloblastoma differentiation, one had choroid plexus carcinoma differentiation, and one had mesenchymal components. Immunohistochemical staining showed that all of the tumors lost the nuclear expression of integrase interactor 1 (INI1), and were positive for Vimentin, S-100 protein and epithelial membrane antigen. One case with no recurrence after 24 months may have benefited from radical excision and postoperative radiotherapy. The other 4 patients died 8, 4, 1 and 1-month respectively after operation without radiotherapy. The diagnosis of AT/RT depends on full sampling, careful observation the morphological characteristics and INI1 examination, even when the tumor are presented in uncommon sites, such as the spinal cord and the pineal region.

Surgical approach to pineal tumours.

PubMed

Pluchino, F; Broggi, G; Fornari, M; Franzini, A; Solero, C L; Allegranza, A

1989-01-01

During a period of 10 years (1977-1986) 40 cases of tumour of the pineal region have been treated at the Istituto Neurologico "C. Besta"-of Milan. Out of these 40 cases, 27 (67.5%) were in the paediatric (10-15 years) or juvenile (15-20 years) age at the time of operation. Since 1983 a specific diagnostic and therapeutic protocol has been adopted and thereafter direct surgical removal of the tumour was performed only when the neuroradiological investigations were highly suggestive of a benign extrinsic lesion. Sixteen cases in this series underwent direct surgical removal; in the remaining 24 cases stereotactic biopsy of the tumour was performed in the first instance. On the basis of the histological diagnosis obtained by this procedure surgical excision of the tumour (9 cases) or radiotherapy (15 cases) was then performed. 25 cases underwent surgical removal of the lesion. In all the cases the infratentorial supracerebellar approach as introduced by Krause and then modified by Stein was adopted. On analysis of the data of this series it was observed that in 25% of the cases completely benign resectable tumours were found; in 25% of the cases astrocytoma (grade I-II) which could be treated at least by partial removal were present; in 30% of the cases radiosensitive lesions were encountered. In the remaining 20% of the cases highly malignant tumours were found which should be treated only by radiotherapy and/or chemotherapy.

Stroke and pineal gland calcification: lack of association. Results from a population-based study (The Atahualpa Project).

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Lama, Julio; Zambrano, Mauricio

2015-03-01

It has been suggested that pineal gland calcifications (PGC) represent a risk factor for stroke; however, information comes from a single retrospective hospital-based registry. We aimed to validate this association in a population-based study conducted in rural Ecuador. Atahualpa residents aged ≥60 years were identified during a door-to-door survey and invited to undergo neuroimaging studies (CT/MRI) for identification and rating PGC and lesions consistent with cerebral infarcts and hemorrhages. Cardiovascular health (CVH) status was assessed according to the American Heart Association criteria, and clinical strokes were identified by the use of a validated field instrument and confirmed by neurologists. Out of 248 participants (mean age 70±8 years, 59% women, 73% with poor CVH), 137 (55%) had PGC and 39 (16%) had strokes (silent in 28 cases). PGC were noted in 61% versus 54% persons with and without stroke, respectively. After adjusting for age, sex and cardiovascular health, logistic and ordinal logistic regression models showed no association between any evidence (p=0.916) or severity (p=0.740) of PGC and stroke. PGC is not associated with stroke in this population of community-dwelling elders, where prevalence of PGC and stroke are similar to those found in other regions. Copyright © 2015 Elsevier B.V. All rights reserved.

[Melatonin, synthetic analogs, and the sleep/wake rhythm].

PubMed

Escames, G; Acuña-Castroviejo, D

Melatonin, a widespread hormone in the animal kingdom, is produced by several organs and tissues besides the pineal gland. Whilst extrapineal melatonin behaves as a cytoprotective molecule, the pineal produces the hormone in a rhythmic manner. The discovery of melatonin in 1958, and the characterization of its synthesis somewhat later, let to the description of its photoperiodic regulation and its relationship with the biological rhythms such as the sleep/wake rhythm. The suprachiasmatic nuclei are the anatomical seat of the biological clock, represented by the clock genes, which code for the period and frequency of the rhythms. The photoperiod synchronizes the activity of the auprachiasmatic biological clock, which in turn induces the melatonin's rhythm. The rhythm of melatonin, peaking at 2-3 am, acts as an endogenous synchronizer that translates the environmental photoperiodic signal in chemical information for the cells. The sleep/wake cycle is a typical biological rhythm synchronized by melatonin, and the sleep/wake cycle alterations of chronobiological origin, are very sensitive to melatonin treatment. Taking advantage of the chronobiotic and antidepressive properties of melatonin, a series of synthetic analogs of this hormone, with high interest in insomnia, are now available. Melatonin is a highly effective chronobiotic in the treatment of chronobiological alterations of the sleep/wake cycle. From a pharmacokinetic point of view, the synthetic drugs derived from melatonin are interesting tools in the therapy of these alterations.

A 15-minute light pulse during darkness prevents the antigonadotrophic action of afternoon melatonin injections in male hamsters

NASA Astrophysics Data System (ADS)

Reiter, R. J.; Hurlbut, E. C.; King, T. S.; Richardson, B. A.; Vaughan, M. K.; Kosub, K. Y.

1982-12-01

When adult male Syrian hamsters were maintained under 14 h light and 10 h darkness daily (lights on from 0600-2000 h), peak pineal melatonin levels (705 pg/gland) were attained at 0500 h. When the dark phase of the light:dark cycle was interrupted with a 15 min pulse of light from 2300 2315 h (3 h after lights out), the highest melatonin levels achieved was roughly 400 pg/gland. Finally, if the 15 min pulse of light was given at 0200 0215 h (6 h after lights out) the nocturnal rise in pineal melatonin was completely abolished. Having made these observations, a second experiment was designed to determine the ability of afternoon melatonin injections to inhibit reproduction in hamsters kept under an uninterrupted 14∶10 cycle or under the same lighting regimen where the dark phase was interrupted with a 15 min pulse of light (0200 0215 h). In the uninterrupted light:dark schedule the daily afternoon injection of 25 μg melatonin caused the testes and the accessory sex organs to atrophy within 11 weeks. Conversely, if the dark phase was interrupted with light between 0200 0215 h, afternoon melatonin injections were incapable of inhibiting the growth of the reproductive organs. The findings suggest that exogenously administered melatonin normally synergizes with endogenously produced melatonin to cause gonadal involution in hamsters.

Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laitinen, J.T.; Castren, E.; Vakkuri, O.

1989-03-01

We used quantitative in vitro autoradiography to localize and characterize 2-/sup 125/I-melatonin binding sites in the rat suprachiasmatic nuclei in relation to pineal melatonin production. In a light:dark cycle of 12:12 h, binding density exhibited significant diurnal variation with a peak at the dark-light transition and a trough 12 hours later. Saturation studies suggested that the decreased binding at light-dark transition might be due to a shift of the putative melatonin receptor to a low affinity state.

Depleting Glycine and Sarcosine in Prostate Cancer Cells as a New Treatment for Advanced Prostate Cancer

DTIC Science & Technology

2015-04-01

expression through a GSK3B-dependent mechanism : a new target for melatonin’s anti-inflammatory action. J Pineal Res. 2013 Nov;55(4):377-87. doi...Myers L, You Z *. Insulin and IGF1 enhance IL- 17-induced chemokine expression through a GSK3B-dependent mechanism : a new target for melatonin’s anti...proliferation and promotion of apoptosis. The molecular mechanism may be that AMPA upregulates the p53 protein level, which subsequently increases p21

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

PubMed

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

[The influence of melatonin and epithalon on blood leukocyte count and leukocyte alkaline phosphatase in rats under different lighting conditions during ontogenesis].

PubMed

Uzenbaeva, L B; Vinogradova, I A; Golubeva, A G; Niuppieva, M G; Iliukha, V A

2008-01-01

The effect of pineal body hormone melatonin and synthetic tetrapeptide epithalon (Ala-Glu-Asp-Gly) under different light conditions on leucocytes differential count in rats were investigated. It has been established that melatonin and epithalon decrease the level of blood leucocytes and relative content of band neutrophils in 12 months rats which was higher in the constant light more than in other photoperiod. The melatonin prevents age-specific decreasing blood lymphocytes level in standard photoperiod (12 h light/12 h darkness). Contrary to melatonin, epithalon significantly reduces the number of lymphocytes and increases the number of neutrophils in some age period. The leucocytes alkaline phosphatase activity was increased during aging. Constant light in compare with other light conditions promotes early increasing of alkaline phosphatase activity (at 12 months), associated with accelerated development of pathological process in organism. The melatonin and epithalon adjacency effect on increasing of alkaline phosphatase activity under the standard as well as natural light condition demonstrate homeostatic character of geroprotectors action furthermore depend on leucocytes functional status.

The circadian clock stops ticking during deep hibernation in the European hamster

PubMed Central

Revel, Florent G.; Herwig, Annika; Garidou, Marie-Laure; Dardente, Hugues; Menet, Jérôme S.; Masson-Pévet, Mireille; Simonneaux, Valérie; Saboureau, Michel; Pévet, Paul

2007-01-01

Hibernation is a fascinating, yet enigmatic, physiological phenomenon during which body temperature and metabolism are reduced to save energy. During the harsh season, this strategy allows substantial energy saving by reducing body temperature and metabolism. Accordingly, biological processes are considerably slowed down and reduced to a minimum. However, the persistence of a temperature-compensated, functional biological clock in hibernating mammals has long been debated. Here, we show that the master circadian clock no longer displays 24-h molecular oscillations in hibernating European hamsters. The clock genes Per1, Per2, and Bmal1 and the clock-controlled gene arginine vasopressin were constantly expressed in the suprachiasmatic nucleus during deep torpor, as assessed by radioactive in situ hybridization. Finally, the melatonin rhythm-generating enzyme, arylalkylamine N-acetyltransferase, whose rhythmic expression in the pineal gland is controlled by the master circadian clock, no longer exhibits day/night changes of expression but constantly elevated mRNA levels over 24 h. Overall, these data provide strong evidence that in the European hamster the molecular circadian clock is arrested during hibernation and stops delivering rhythmic output signals. PMID:17715068

Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases

PubMed Central

Permuy, Maria; López-Peña, Mónica; González-Cantalapiedra, Antonio; Muñoz, Fernando

2017-01-01

Melatonin is a hormone synthesised and secreted by the pineal gland and other organs. Its secretion, controlled by an endogenous circadian cycle, has been proven to exert immunological, anti-oxidant, and anti-inflammatory effects that can be beneficial in the treatment of certain dental diseases. This article is aimed at carrying out a review of the literature published about the use of melatonin in the dental field and summarising its potential effects. In this review article, an extensive search in different databases of scientific journals was performed with the objective of summarising all of the information published on melatonin use in dental diseases, focussing on periodontal diseases and dental implantology. Melatonin released in a natural way into the saliva, or added as an external treatment, may have important implications for dental disorders, such as periodontal disease, as well as in the osseointegration of dental implants, due to its anti-inflammatory and osseoconductive effects. Melatonin has demonstrated to have beneficial effects on dental pathologies, although further research is needed to understand the exact mechanisms of this molecule. PMID:28422058

A comparison of epithalamic, hypothalamic and spinal neurosecretory terminals.

PubMed

Vigh-Teichmann, I; Vigh, B

1979-01-01

Nerve endings of epithalamic, hypothalamic and spinal neurosecretory areas were studied by light and electron microscopy in various vertebrates (from fishes up to mammals) including the lancelet. Areas investigated were the pineal organ, the pulvinar corporis pinealis, the neurohypophysis, the median eminence, the urophysis, the terminal filum and the medullo-spinal neurosecretory zones. We found that in all these areas the neurosecretory endings have common structures, which we call synaptic hemidesmosomes or neurohormonal terminals. These are characterized by accumulation of vesicles, and dense projections in a terminal on the basal lamina of the surface of the nervous tissue. A critical review of the literature suggests that a considerble neuroendocrine activity is associated with synaptic hemidesmosomes as special neurohormonal effector structures of the nerve cells. The cell-to-cell synapses formed by neurosecretory cells are discussed in connection with the dual capacity of these cells to function as both endocrine and "ordinary# neuronal elements. The importance of the external cerebrospinal fluid (CSF) space for the transport of materials released in the so-called neurohemal areas, is stressed.

Melatonin and female reproduction.

PubMed

Tamura, Hiroshi; Takasaki, Akihisa; Taketani, Toshiaki; Tanabe, Manabu; Lee, Lifa; Tamura, Isao; Maekawa, Ryo; Aasada, Hiromi; Yamagata, Yoshiaki; Sugino, Norihiro

2014-01-01

Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by the pineal gland. After entering the circulation, melatonin acts as an endocrine factor and a chemical messenger of light and darkness. It regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It also affects the brain, immune, gastrointestinal, cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and anti-aging molecule. Many of melatonin's actions are mediated through interactions with specific membrane-bound receptors expressed not only in the central nervous system, but also in peripheral tissues. Melatonin also acts through non-receptor-mediated mechanisms, for example serving as a scavenger for reactive oxygen species and reactive nitrogen species. At both physiological and pharmacological concentrations, melatonin attenuates and counteracts oxidative stress and regulates cellular metabolism. Growing scientific evidence of reproductive physiology supports the role of melatonin in human reproduction. This review was conducted to investigate the effects of melatonin on female reproduction and to summarize our findings in this field. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

PubMed Central

Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

2014-01-01

This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. PMID:25032843

The role of melatonin in pancreatic protection: could melatonin be used in the treatment of acute pancreatitis?

PubMed

Jaworek, Jolanta; Leja-Szpak, Anna; Kot, Michalina; Jaworek, Andrzej; Nawrot-Porbka, Katarzyna; Bonior, Joanna; Szklarczyk, Joanna

2014-01-01

Acute pancreatitis is a disease, which could be manifested as either a mild edematous form or a more severe necrotizing pancreatitis which has a poor prognosis. The etiology and pathogenesis of this ailment is not completely clear. Melatonin is an indoleamine which is produced from L-tryptophan in the pineal gland and in the other tissue including gastrointestinal tract. Both melatonin and its precursor have been demonstrated to protect the pancreas against acute pancreatitis and to attenuate pancreatic tissue damage. In the pancreas melatonin and L-tryptophan activate complex mechanisms which involve direct scavenging of the radical oxygen and nitrogen species, activation of antioxidant enzymes (catalase, superoxide dysmutase, glutation peroxidase), reduction of pro-inflammatory cytokines and prostaglandins, activation of heat shock protein, and a decrease of necrosis and increase of regeneration in the pancreas. There are several arguments for the idea that endogenous melatonin produced in the pineal gland and in the gastrointestinal system could be the part of a native mechanisms for protecting the pancreas against acute damage: 1/ the melatonin precursor L-tryptophan exerts similar protective effect as melatonin, 2/ application of the melatonin receptor antagonist, luzindole aggravates acute pancreatitis, 3/ pinealectomy results in the exacerbation of acute pancreatitis, 4/ low melatonin plasma levels are associated with an increased risk of severe acute pancreatitis. These observations leads to the idea that perhaps melatonin could be used in clinical trials as supportive therapy in acute pancreatitis.

Brain dose-sparing radiotherapy techniques for localized intracranial germinoma: Case report and literature review of modern irradiation.

PubMed

Leung, H W C; Chan, A L F; Chang, M B

2016-05-01

We examined the effects of intensity-modulated radiation therapy with dose-sparing and avoidance technique on a pediatric patient with localized intracranial germinoma. We also reviewed the literature regarding modern irradiation techniques in relation to late neurocognitive sequelae. A patient with a localized intracranial germinoma in the third ventricle anterior to the pineal gland received a dose-sparing intensity-modulated radiation therapy. The planning was compared to the radiation oncologist's guide of organs at risk and dose constraints for dosimetric analyses. The patient received radiation therapy alone. The total dose was 54Gy delivered in 2.0Gy fractions to the primary tumour and 37Gy in 1.4Gy fractions to whole ventricles using a dose-sculpting plan. Dosimetry analyses showed that dose-sparing intensity-modulated radiation therapy delivered reduced doses to the whole brain, temporal lobes, hippocampi, cochleae, and optic nerves. With a follow-up of 22 months, failure-free survival was 100% for the patient and no adverse events during radiation treatment process. Intensity-modulated radiation therapy with dose sparing and avoidance technique can spare the limbic circuit, central nervous system, and hippocampus for pineal germ cell tumours. This technique reduces the integral dose delivered to the uninvolved normal brain tissues and may reduce late neurocognitive sequelae caused by cranial radiotherapy. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies.

PubMed

Sakowski, Stacey A; Geddes, Timothy J; Thomas, David M; Levi, Edi; Hatfield, James S; Kuhn, Donald M

2006-04-26

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of the neurotransmitter serotonin. Once thought to be a single-gene product, TPH is now known to exist in two isoforms-TPH1 is found in the pineal and gut, and TPH2 is selectively expressed in brain. Heretofore, probes used for localization of TPH protein or mRNA could not distinguish between the TPH isoforms because of extensive homology shared by them at the nucleotide and amino acid level. We have produced monospecific polyclonal antibodies against TPH1 and TPH2 using peptide antigens from nonoverlapping sequences in the respective proteins. These antibodies allow the differentiation of TPH1 and TPH2 upon immunoblotting, immunoprecipitation, and immunocytochemical staining of tissue sections from brain and gut. TPH1 and TPH2 antibodies do not cross-react with either tyrosine hydroxylase or phenylalanine hydroxylase. Analysis of mouse tissues confirms that TPH1 is the predominant form expressed in pineal gland and in P815 mastocytoma cells with a molecular weight of 51 kDa. TPH2 is the predominant enzyme form expressed in brain extracts from mesencephalic tegmentum, striatum, and hippocampus with a molecular weight of 56 kDa. Antibody specificity against TPH1 and TPH2 is retained across mouse, rat, rabbit, primate, and human tissues. Antibodies that distinguish between the isoforms of TPH will allow studies of the differential regulation of their expression in brain and periphery.

Analysis of miRNA expression profiles in melatonin-exposed GC-1 spg cell line.

PubMed

Zhu, Xiaoling; Chen, Shuxiong; Jiang, Yanwen; Xu, Ying; Zhao, Yun; Chen, Lu; Li, Chunjin; Zhou, Xu

2018-02-05

Melatonin is an endocrine neurohormone secreted by pinealocytes in the pineal gland. It exerts diverse physiological effects, such as circadian rhythm regulator and antioxidant. However, the functional importance of melatonin in spermatogenesis regulation remains unclear. The objectives of this study are to: (1) detect melatonin affection on miRNA expression profiles in GC-1 spg cells by miRNA deep sequencing (DeepSeq) and (2) define melatonin affected miRNA-mRNA interactions and associated biological processes using bioinformatics analysis. GC-1 spg cells were cultured with melatonin (10 -7 M) for 24h. DeepSeq data were validated using quantitative real-time reverse transcription polymerase chain reaction analysis (qRT-PCR). A total of 176 miRNA expressions were found to be significantly different between two groups (fold change of >2 or <0.5 and FDR<0.05). Among these expressions, 171 were up-regulated, and 5 were down-regulated. Ontology analysis of biological processes of these targets indicated a variety of biological functions. Pathway analysis indicated that the predicted targets were involved in cancers, apoptosis and signaling pathways, such as VEGF, TNF, Ras and Notch. Results implicated that melatonin could regulate the expression of miRNA to perform its physiological effects in GC-1 spg cells. These results should be useful to investigate the biological function of miRNAs regulated by melatonin in spermatogenesis and testicular germ cell tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution, function and physiological role of melatonin in the lower gut

PubMed Central

Chen, Chun-Qiu; Fichna, Jakub; Bashashati, Mohammad; Li, Yong-Yu; Storr, Martin

2011-01-01

Melatonin is a hormone with endocrine, paracrine and autocrine actions. It is involved in the regulation of multiple functions, including the control of the gastrointestinal (GI) system under physiological and pathophysiological conditions. Since the gut contains at least 400 times more melatonin than the pineal gland, a review of the functional importance of melatonin in the gut seems useful, especially in the context of recent clinical trials. Melatonin exerts its physiological effects through specific membrane receptors, named melatonin-1 receptor (MT1), MT2 and MT3. These receptors can be found in the gut and their involvement in the regulation of GI motility, inflammation and pain has been reported in numerous basic and clinical studies. Stable levels of melatonin in the lower gut that are unchanged following a pinealectomy suggest local synthesis and, furthermore, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut. PMID:22025877

Effects of LED-backlit computer screen and emotional selfregulation on human melatonin production.

PubMed

Sroykham, Watchara; Wongsawat, Yodchanan

2013-01-01

Melatonin is a circadian hormone transmitted via suprachiasmatic nucleus (SCN) in the hypothalamus and sympathetic nervous system to the pineal gland. It is a hormone necessary to many human functions such as immune, cardiovascular, neuron and sleep/awake functions. Since melatonin enhancement or suppression is reported to be closely related to the photic information from retina, in this paper, we aim further to study both the lighting condition and the emotional self-regulation in different lighting conditions together with their effects on the production of human melatonin. In this experiment, five participants are in three light exposure conditions by LED backlit computer screen (No light, Red light (∼650nm) and Blue light (∼470nm)) for 30 minute (8-8:30pm), then they are collected saliva both before and after the experiments. After the experiment, the participants are also asked to answer the emotional self-regulation questionnaire of PANAS and BRUMS regarding each light exposure condition. These results show that positive mood mean difference of PANAS between no light and red light is significant with p=0.001. Tension, depression, fatigue, confusion and vigor from BRUMS are not significantly changed while we can observe the significant change in anger mood. Finally, we can also report that the blue light of LED-backlit computer screen significantly suppress melatonin production (91%) more than red light (78%) and no light (44%).

Papillary tumor of the pineal region: two case studies and a review of the literature.

PubMed

Rickard, Kyle A; Parker, John R; Vitaz, Todd W; Plaga, Alexis R; Wagner, Stephanie; Parker, Joseph C

2011-01-01

Papillary tumor of the pineal region (PTPR) is a newly recognized distinct entity in the 2007 World Health Organization nomenclature. This tumor is characterized by epithelial-appearing areas with papillary features and more densely cellular areas that often display ependymal-like differentiation. Ultrastructurally, this rare neuroepithelial tumor possesses neuroendocrine, secretory, and ependymal organelles that likely originate from the subcommissural organ (SCO) near the aqueduct of Sylvius. To date, approximately fifty-seven described cases worldwide have been recognized, with ages ranging from 5 years to 66 years (mean age=32 years). Clinical presentation most often includes headache and obstructive hydrocephalus. The tumor, which is well circumscribed, may be cystic and radiographically is often considered to be consistent with the findings of a pineocytoma. Microscopic evaluation often demonstrates a lesion with papillary areas lined by epithelioid tumor cells with eosinophilic cytoplasm and more cellular areas with cells exhibiting clear or vacuolated cytoplasm. Perivascular and true rosettes may be identified. Distinctive immunohistochemical features including reactivity for keratins (AE1/AE3, CAM 5.2, CK18) and only focal GFAP staining help distinguish this neoplasm from an ependymoma. The relative paucity of data compiled for this tumor makes giving an accurate diagnosis and prognosis a daunting task. We discuss two additional cases of PTPR that presented to us within a three-month span in order to more fully elucidate the possible presentations of this rare entity. Furthermore, we examine now 59 reported cases of PTPR in order to review the current diagnostic and treatment modalities in addition to exploring emerging research encompassing this unusual neoplasm.

Diagnostic accuracy of susceptibility-weighted magnetic resonance imaging for the evaluation of pineal gland calcification

PubMed Central

Böker, Sarah M.; Bender, Yvonne Y.; Diederichs, Gerd; Fallenberg, Eva M.; Wagner, Moritz; Hamm, Bernd; Makowski, Marcus R.

2017-01-01

Objectives To determine the diagnostic performance of susceptibility-weighted magnetic resonance imaging (SWMR) for the detection of pineal gland calcifications (PGC) compared to conventional magnetic resonance imaging (MRI) sequences, using computed tomography (CT) as a reference standard. Methods 384 patients who received a 1.5 Tesla MRI scan including SWMR sequences and a CT scan of the brain between January 2014 and October 2016 were retrospectively evaluated. 346 patients were included in the analysis, of which 214 showed PGC on CT scans. To assess correlation between imaging modalities, the maximum calcification diameter was used. Sensitivity and specificity and intra- and interobserver reliability were calculated for SWMR and conventional MRI sequences. Results SWMR reached a sensitivity of 95% (95% CI: 91%-97%) and a specificity of 96% (95% CI: 91%-99%) for the detection of PGC, whereas conventional MRI achieved a sensitivity of 43% (95% CI: 36%-50%) and a specificity of 96% (95% CI: 91%-99%). Detection rates for calcifications in SWMR and conventional MRI differed significantly (95% versus 43%, p<0.001). Diameter measurements between SWMR and CT showed a close correlation (R2 = 0.85, p<0.001) with a slight but not significant overestimation of size (SWMR: 6.5 mm ± 2.5; CT: 5.9 mm ± 2.4, p = 0.02). Interobserver-agreement for diameter measurements was excellent on SWMR (ICC = 0.984, p < 0.0001). Conclusions Combining SWMR magnitude and phase information enables the accurate detection of PGC and offers a better diagnostic performance than conventional MRI with CT as a reference standard. PMID:28278291

Sympathetic reinnervation of peripheral targets following bilateral axotomy of the adult superior cervical ganglion

PubMed Central

Hesp, Zoe C.; Zhu, Zheng; Morris, Teresa A.; Walker, Ryan G.; Isaacson, L.G.

2012-01-01

The ability of adult injured postganglionic axons to reinnervate cerebrovascular targets is unknown, yet these axons can influence cerebral blood flow, particularly during REM sleep. The objective of the present study was to assess quantitatively the sympathetic reinnervation of vascular as well as non-vascular targets following bilateral axotomy of the superior cervical ganglion (SCG) at short term (1 day, 7 days) and long term (8 weeks, 12 weeks) survival time points. The sympathetic innervation of representative extracerebral blood vessels [internal carotid artery (ICA), basilar artery (BA), middle cerebral artery (MCA)], the submandibular gland (SMG), and pineal gland was quantified following injury using an antibody to tyrosine hydroxylase (TH). Changes in TH innervation were related to TH protein content in the SCG. At 7 days following bilateral SCG axotomy, all targets were significantly depleted of TH innervation, and the exact site on the BA where SCG input was lost could be discerned. Complete sympathetic reinnervation of the ICA was observed at long term survival times, yet TH innervation of other vascular targets showed significant decreases even at 12 weeks following axotomy. The SMG was fully reinnervated by 12 weeks, yet TH innervation of the pineal gland remained significantly decreased. TH protein in the SCG was significantly decreased at both short term and long term time points and showed little evidence of recovery. Our data demonstrate a slow reinnervation of most vascular targets following axotomy of the SCG with only minimal recovery of TH protein in the SCG at 12 weeks following injury. PMID:22842079

Neurosurgical endoscopic training via a realistic 3-dimensional model with pathology.

PubMed

Waran, Vicknes; Narayanan, Vairavan; Karuppiah, Ravindran; Thambynayagam, Hari Chandran; Muthusamy, Kalai Arasu; Rahman, Zainal Ariff Abdul; Kirollos, Ramez Wadie

2015-02-01

Training in intraventricular endoscopy is particularly challenging because the volume of cases is relatively small and the techniques involved are unlike those usually used in conventional neurosurgery. Present training models are inadequate for various reasons. Using 3-dimensional (3D) printing techniques, models with pathology can be created using actual patient's imaging data. This technical article introduces a new training model based on a patient with hydrocephalus secondary to a pineal tumour, enabling the models to be used to simulate third ventriculostomies and pineal biopsies. Multiple models of the head of a patient with hydrocephalus were created using 3D rapid prototyping technique. These models were modified to allow for a fluid-filled ventricular system under appropriate tension. The models were qualitatively assessed in the various steps involved in an endoscopic third ventriculostomy and intraventricular biopsy procedure, initially by 3 independent neurosurgeons and subsequently by 12 participants of an intraventricular endoscopy workshop. All 3 surgeons agreed on the ease and usefulness of these models in the teaching of endoscopic third ventriculostomy, performing endoscopic biopsies, and the integration of navigation to ventriculoscopy. Their overall score for the ventricular model realism was above average. The 12 participants of the intraventricular endoscopy workshop averaged between a score of 4.0 to 4.6 of 5 for every individual step of the procedure. Neurosurgical endoscopic training currently is a long process of stepwise training. These 3D printed models provide a realistic simulation environment for a neuroendoscopy procedure that allows safe and effective teaching of navigation and endoscopy in a standardized and repetitive fashion.

Understanding Brain, Mind and Soul: Contributions from Neurology and Neurosurgery

PubMed Central

Pandya, Sunil K.

2011-01-01

Treatment of diseases of the brain by drugs or surgery necessitates an understanding of its structure and functions. The philosophical neurosurgeon soon encounters difficulties when localising the abstract concepts of mind and soul within the tangible 1300-gram organ containing 100 billion neurones. Hippocrates had focused attention on the brain as the seat of the mind. The tabula rasa postulated by Aristotle cannot be localised to a particular part of the brain with the confidence that we can localise spoken speech to Broca’s area or the movement of limbs to the contralateral motor cortex. Galen’s localisation of imagination, reasoning, judgement and memory in the cerebral ventricles collapsed once it was evident that the functional units–neurones–lay in the parenchyma of the brain. Experiences gained from accidental injuries (Phineas Gage) or temporal lobe resection (William Beecher Scoville); studies on how we see and hear and more recent data from functional magnetic resonance studies have made us aware of the extensive network of neurones in the cerebral hemispheres that subserve the functions of the mind. The soul or atman, credited with the ability to enliven the body, was located by ancient anatomists and philosophers in the lungs or heart, in the pineal gland (Descartes), and generally in the brain. When the deeper parts of the brain came within the reach of neurosurgeons, the brainstem proved exceptionally delicate and vulnerable. The concept of brain death after irreversible damage to it has made all of us aware of ‘the cocktail of brain soup and spark’ in the brainstem so necessary for life. If there be a soul in each of us, surely, it is enshrined here. PMID:21694966

Evolution and functional characterisation of melanopsins in a deep-sea chimaera (elephant shark, Callorhinchus milii).

PubMed

Davies, Wayne I L; Tay, Boon-Hui; Zheng, Lei; Danks, Janine A; Brenner, Sydney; Foster, Russell G; Collin, Shaun P; Hankins, Mark W; Venkatesh, Byrappa; Hunt, David M

2012-01-01

Non-visual photoreception in mammals is primarily mediated by two splice variants that derive from a single melanopsin (OPN4M) gene, whose expression is restricted to a subset of retinal ganglion cells. Physiologically, this sensory system regulates the photoentrainment of many biological rhythms, such as sleep via the melatonin endocrine system and pupil constriction. By contrast, melanopsin exists as two distinct lineages in non-mammals, opn4m and opn4x, and is broadly expressed in a wide range of tissue types, including the eye, brain, pineal gland and skin. Despite these findings, the evolution and function of melanopsin in early vertebrates are largely unknown. We, therefore, investigated the complement of opn4 classes present in the genome of a model deep-sea cartilaginous species, the elephant shark (Callorhinchus milii), as a representative vertebrate that resides at the base of the gnathostome (jawed vertebrate) lineage. We reveal that three melanopsin genes, opn4m1, opn4m2 and opn4x, are expressed in multiple tissues of the elephant shark. The two opn4m genes are likely to have arisen as a result of a lineage-specific duplication, whereas "long" and "short" splice variants are generated from a single opn4x gene. By using a heterologous expression system, we suggest that these genes encode functional photopigments that exhibit both "invertebrate-like" bistable and classical "vertebrate-like" monostable biochemical characteristics. We discuss the evolution and function of these melanopsin pigments within the context of the diverse photic and ecological environments inhabited by this chimaerid holocephalan, as well as the origin of non-visual sensory systems in early vertebrates.

Evolution and Functional Characterisation of Melanopsins in a Deep-Sea Chimaera (Elephant Shark, Callorhinchus milii)

PubMed Central

Davies, Wayne I. L.; Tay, Boon-Hui; Zheng, Lei; Danks, Janine A.; Brenner, Sydney; Foster, Russell G.; Collin, Shaun P.; Hankins, Mark W.; Venkatesh, Byrappa; Hunt, David M.

2012-01-01

Non-visual photoreception in mammals is primarily mediated by two splice variants that derive from a single melanopsin (OPN4M) gene, whose expression is restricted to a subset of retinal ganglion cells. Physiologically, this sensory system regulates the photoentrainment of many biological rhythms, such as sleep via the melatonin endocrine system and pupil constriction. By contrast, melanopsin exists as two distinct lineages in non-mammals, opn4m and opn4x, and is broadly expressed in a wide range of tissue types, including the eye, brain, pineal gland and skin. Despite these findings, the evolution and function of melanopsin in early vertebrates are largely unknown. We, therefore, investigated the complement of opn4 classes present in the genome of a model deep-sea cartilaginous species, the elephant shark (Callorhinchus milii), as a representative vertebrate that resides at the base of the gnathostome (jawed vertebrate) lineage. We reveal that three melanopsin genes, opn4m1, opn4m2 and opn4x, are expressed in multiple tissues of the elephant shark. The two opn4m genes are likely to have arisen as a result of a lineage-specific duplication, whereas “long” and “short” splice variants are generated from a single opn4x gene. By using a heterologous expression system, we suggest that these genes encode functional photopigments that exhibit both “invertebrate-like” bistable and classical “vertebrate-like” monostable biochemical characteristics. We discuss the evolution and function of these melanopsin pigments within the context of the diverse photic and ecological environments inhabited by this chimaerid holocephalan, as well as the origin of non-visual sensory systems in early vertebrates. PMID:23251480

RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

ClinicalTrials.gov

2015-09-28

Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

ClinicalTrials.gov

2017-03-22

Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

[Teratoma and medulloblastoma of the cerebellum: a case].

PubMed

Boudawara, T; Boudawara, M Z; Sellami, M H; Ben Mansour, H; Jlidi, R

1999-01-01

The majority of intracranial teratoma are localized in pineal and sellar regions. In cerebellum, the teratoma is quite rare, the association with medulloblastoma is exceptional and was differentiated from medullomyoblastoma. We report one case of 5 years old boy with intracranial hypertension for 3 months. The cerebral computed tomography showed a tumor in the fourth ventricle. The histologic study of surgical specimens found a proliferation of component of medulloblastoma adjacent to mature teratoma with smooth and striated muscles, chondroid component, adipose tissue and epithelial elements. Our objective is to discuss the diagnosis, the hitogenesis and the prognosis of this tumor.

New findings regarding light intensity and its effects as a zeitgeber in the Sprague-Dawley rat

NASA Technical Reports Server (NTRS)

Tischler, A. C.; Winget, C. M.; Holley, D. C.; Deroshia, C. W.; Gott, J.; Mele, G.; Callahan, P. X.

1993-01-01

In most mammals, the suprachiasmatic nucleus of the anterior hypothalamus has been implicated as the central driving mechanism of circadian rhythmicity. The photic input from the retina, via the retino-hypothalamic tract, and modulation from the pineal gland help regulate the clock. In this study, we investigated the effects of low light intensity on the circadian system of the Sprague-Dawley rat. A series of light intensity experiments were conducted to determine if a light level of 0.1 Lux will maintain entrained circadian rhythms of feeding, drinking, and locomotor activity.

Red light is necessary to activate the reproductive axis in chickens independently of the retina of the eye.

PubMed

Baxter, M; Joseph, N; Osborne, V R; Bédécarrats, G Y

2014-05-01

Photoperiod is essential in manipulating sexual maturity and reproductive performance in avian species. Light can be perceived by photoreceptors in the retina of the eye, pineal gland, and hypothalamus. However, the relative sensitivity and specificity of each organ to wavelength, and consequently the physiological effects, may differ. The purpose of this experiment was to test the impacts of light wavelengths on reproduction, growth, and stress in laying hens maintained in cages and to determine whether the retina of the eye is necessary. Individual cages in 3 optically isolated sections of a single room were equipped with LED strips providing either pure green, pure red or white light (red, green, and blue) set to 10 lx (hens levels). The involvement of the retina on mediating the effects of light wavelength was assessed by using a naturally blind line (Smoky Joe) of chickens. Red and white lights resulted in higher estradiol concentrations after photostimulation, indicating stronger ovarian activation, which translated into a significantly lower age at first egg when compared with the green light. Similarly, hens maintained under red and white lights had a longer and higher peak production and higher cumulative egg number than hens under green light. No significant difference in BW gain was observed until sexual maturation. However, from 23 wk of age onward, birds exposed to green light showed higher body growth, which may be the result of their lower egg production. Although corticosterone levels were higher at 20 wk of age in hens under red light, concentrations were below levels that can be considered indicative of stress. Because no significant differences were observed between blind and sighted birds maintained under red and white light, the retina of the eye did not participate in the activation of reproduction. In summary, red light was required to stimulate the reproductive axis whereas green light was ineffective, and the effects of stimulatory wavelengths do not appear to require a functional retina of the eye.

Melatonin transport into mitochondria.

PubMed

Mayo, Juan C; Sainz, Rosa M; González-Menéndez, Pedro; Hevia, David; Cernuda-Cernuda, Rafael

2017-11-01

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole's protective actions. Melatonin's mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.

The habenula in neurosurgery for depression: A convergence of functional neuroanatomy, psychiatry and imaging.

PubMed

Skandalakis, Georgios P; Koutsarnakis, Christos; Kalyvas, Aristotelis V; Skandalakis, Panagiotis; Johnson, Elizabeth O; Stranjalis, George

2018-05-05

The habenula is a small, mostly underrated structure in the pineal region. Multidisciplinary findings demonstrate an underlying complex connectivity of the habenula with the rest of the brain, subserving its major role in normal behavior and the pathophysiology of depression. These findings suggest the potential application of "habenular psychosurgery" in the treatment of mental disorders. The remission of two patients with treatment-resistant major depression treated with deep brain stimulation of the habenula supported the hypothesis that the habenula is an effective target for deep brain stimulation and initiated a surge of basic science research. This review aims to assess the viability of the deep brain stimulation of the habenula as a treatment option for treatment resistant depression. PubMed and the Cochrane Library databases were searched with no chronological restrictions for the identification of relevant articles. The results of this review are presented in a narrative form describing the functional neuroanatomy of the human habenula, its implications in major depression, findings of electrode implantation of this region and findings of deep brain stimulation of the habenula for the treatment of depression. Data assessing the hypothesis are scarce. Nonetheless, findings highlight the major role of the habenula in normal, as well as in pathological brain function, particularly in depression disorders. Moreover, findings of studies utilizing electrode implantation in the region of the habenula underscore our growing realization that research in neuroscience and deep brain stimulation complement each other in a reciprocal relationship; they are as self-reliant, as much as they depend on each other. Copyright © 2018. Published by Elsevier B.V.

Phosducin-like protein: an ethanol-responsive potential modulator of guanine nucleotide-binding protein function.

PubMed

Miles, M F; Barhite, S; Sganga, M; Elliott, M

1993-11-15

Acute and chronic exposure to ethanol produces specific changes in several signal transduction cascades. Such alterations in signaling are thought to be a crucial aspect of the central nervous system's adaptive response, which occurs with chronic exposure to ethanol. We have recently identified and isolated several genes whose expression is specifically induced by ethanol in neural cell cultures. The product of one of these genes has extensive sequence homology to phosducin, a phosphoprotein expressed in retina and pineal gland that modulates trimeric guanine nucleotide-binding protein (G protein) function by binding to G-protein beta gamma subunits. We identified from a rat brain cDNA library an isolate encoding the phosducin-like protein (PhLP), which has 41% identity and 65% amino acid homology to phosducin. PhLP cDNA is expressed in all tissues screened by RNA blot-hybridization analysis and shows marked evolutionary conservation on Southern hybridization. We have identified four forms of PhLP cDNA varying only in their 5' ends, probably due to alternative splicing. This 5'-end variation generates two predicted forms of PhLP protein that differ by 79 aa at the NH2 terminus. Treatment of NG108-15 cells for 24 hr with concentrations of ethanol seen in actively drinking alcoholics (25-100 mM) causes up to a 3-fold increase in PhLP mRNA levels. Induction of PhLP by ethanol could account for at least some of the widespread alterations in signal transduction and G-protein function that are known to occur with chronic exposure to ethanol.

TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level.

PubMed

Alkozi, Hanan Awad; Perez de Lara, Maria J; Sánchez-Naves, Juan; Pintor, Jesús

2017-04-01

Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymine N -acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied. Several experiments were undertaken to verify the adequate time to reach the maximal effect by using the TRPV4 agonist GSK1016790A, together with a dose-response study. An increase of 2.4 folds in AANAT was seen after 18 h of incubation with 10 nM of GSK1016790A ( p < 0.001, n = 6). This increment was verified by antagonist assays. In summary, AANAT levels and therefore melatonin synthesis change after TRPV4 channel stimulation. Using this cell model together with human ciliary body tissue it is possible to suggest that AANAT plays an important role in pathologies related to intraocular pressure.

Radiofrequency (RF) effects on blood cells, cardiac, endocrine, and immunological functions.

PubMed

Black, David R; Heynick, Louis N

2003-01-01

Effects of radiofrequency electromagnetic fields (RFEMF) on the pituitary adrenocortical (ACTH), growth (GH), and thyroid (TSH) hormones have been extensively studied, and there is coherent research on reproductive hormones (FSH and LH). Those effects which have been identified are clearly caused by heating. The exposure thresholds for these effects in living mammals, including primates, have been established. There is limited evidence that indicates no interaction between RFEMF and the pineal gland or an effect on prolactin from the pituitary gland. Studies of RFEMF exposed blood cells have shown that changes or damage do not occur unless the cells are heated. White cells (leukocytes) are much more sensitive than red cells (erythrocytes) but white cell effects remain consistent with normal physiological responses to systemic temperature fluctuation. Lifetime studies of RFEMF exposed animals show no cumulative adverse effects in their endocrine, hematological, or immune systems. Cardiovascular tissue is not directly affected adversely in the absence of significant RFEMF heating or electric currents. The regulation of blood pressure is not influenced by ultra high frequency (UHF) RFEMF at levels commonly encountered in the use of mobile communication devices. Copyright 2003 Wiley-Liss, Inc.

Melatonin-mediated β-catenin activation protects neuron cells against prion protein-induced neurotoxicity.

PubMed

Jeong, Jae-Kyo; Lee, Ju-Hee; Moon, Ji-Hong; Lee, You-Jin; Park, Sang-Youel

2014-11-01

Activation of β-catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation of β-catenin. In this study, melatonin increased β-catenin protein expression and activation in human neuroblastoma cell lines SH-SY5Y cells. Melatonin also inhibited PrP (106-126)-induced neurotoxicity and the inhibition attenuated by treatment of β-catenin inhibitor ICG-001. Activation of β-catenin blocked PrP (106-126)-mediated downregulation of anti-apoptotic protein survivin and Bcl-2. Reduction of mitochondrial membrane potential, translocation of Bax, and cytochrome c release which induced by PrP (106-126) treatment were inhibited by β-catenin activation, which contributed to prevented PrP (106-126)-induced neuronal cell death. In conclusion, β-catenin activation by melatonin prevented PrP (106-126)-induced neuronal cell death through regulating anti-apoptotic proteins and mitochondrial pathways. These results also suggest the therapeutic value of Wnt/β-catenin signaling in prion-related disorders as influenced by melatonin. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-inflammatory effects of Melatonin: a mechanistic review.

PubMed

Nabavi, Seyed Mohammad; Nabavi, Seyed Fazel; Sureda, Antoni; Xiao, Janbo; Dehpour, Ahmad Reza; Shirooie, Samira; Silva, Ana Sanches; Baldi, Alessandra; Khan, Haroon; Daglia, Maria

2018-06-14

N-acetyl-5-methoxy-tryptamine (melatonin) is a natural substance produced both by plants, as a secondary metabolite, and animals, by the pineal gland and other tissues. In humans, melatonin participates in numerous functions including the regulation of mood, sleep, reproduction, promotion of immunomodulation, antioxidant defense and as an anti-inflammatory agent. The anti-inflammatory activity of melatonin could yield beneficial effects on intake, particularly against the chronic inflammation which underlies many chronic diseases. This review aims to provide an assessment of the literature data on the anti-inflammatory activity of melatonin, with a particular focus on the mechanisms responsible for this behavior. We can conclude that many in vitro studies and in vivo studies in experimental animal model systems show that melatonin exerts anti-inflammatory activity in a number of chronic diseases which affect different organs in different circumstances. Clinical trials, however, often fail to reach positive results and are thus far inconclusive. Thus, in the future, long-term well-designed investigations on melatonin-rich foods or melatonin food supplements could provide valuable information towards public health recommendations on melatonin, taking into account both the nature of the compound and the optimal dose, for protection from long-term inflammation linked to chronic diseases.

The melatonin-MT1 receptor axis modulates tumor growth in PTEN-mutated gliomas.

PubMed

Ma, Huihui; Wang, Zhen; Hu, Lei; Zhang, Shangrong; Zhao, Chenggang; Yang, Haoran; Wang, Hongzhi; Fang, Zhiyou; Wu, Lijun; Chen, Xueran

2018-02-19

More than 40% of glioma patients have tumors that harbor PTEN (phosphatase and tensin homologue deleted on chromosome ten) mutations; this disease is associated with poor therapeutic resistance and outcome. Such mutations are linked to increased cell survival and growth, decreased apoptosis, and drug resistance; thus, new therapeutic strategies focusing on inhibiting glioma tumorigenesis and progression are urgently needed. Melatonin, an indolamine produced and secreted predominantly by the pineal gland, mediates a variety of physiological functions and possesses antioxidant and antitumor properties. Here, we analyzed the relationship between PTEN and the inhibitory effect of melatonin in primary human glioma cells and cultured glioma cell lines. The results showed that melatonin can inhibit glioma cell growth both in culture and in vivo. This inhibition was associated with PTEN levels, which significantly correlated with the expression level of MT1 in patients. In fact, c-fos-mediated MT1 was shown to be a key modulator of the effect of melatonin on gliomas that harbor wild type PTEN. Taken together, these data suggest that melatonin-MT1 receptor complexes represent a potential target for the treatment of glioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Melatonin inhibits the development of 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kim, Tae-Ho; Jung, Jung-A; Kim, Gun-Dong; Jang, An-Hee; Ahn, Hyun-Jong; Park, Yong Seek; Park, Cheung-Seog

2009-11-01

Atopic dermatitis (AD) is a common disease in children, and epicutaneous treatment with a chemical hapten such as 2,4-dinitrofluorobenzene (DNFB) evokes an AD-like reaction in NC/Nga mice under specific pathogen-free conditions. Melatonin (N-acetyl-5-methoxytryptamine) is synthesized by the pineal gland, has several different physiologic functions, which include seasonal reproduction control, immune system modulation, free radical scavenging, and inflammatory suppression. In the present study, we investigated whether melatonin suppresses DNFB-induced AD-like skin lesions in NC/Nga mice. The topical administration of melatonin to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. Furthermore, interleukin (IL)-4 and interferon (IFN)-gamma secretion by activated CD4(+) T cells from the draining lymph nodes of DNFB-treated NC/Nga mice were significantly inhibited by melatonin, and total IgE levels in serum were reduced. Our findings suggest that melatonin suppresses the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing total IgE in serum, and IL-4 and IFN-gamma production by activated CD4(+) T cells.

Radiation Is an Important Component of Multimodality Therapy for Pediatric Non-Pineal Supratentorial Primitive Neuroectodermal Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

McBride, Sean M.; Daganzo, Sally M.; Banerjee, Anuradha

Purpose: To review a historical cohort of pediatric patients with supratentorial primitive neuroectodermal tumors (sPNET), to clarify the role of radiation in the treatment of these tumors. Patients and Methods: Fifteen children aged <18 years with non-pineal sPNETs diagnosed between 1992 and 2006 were identified. Initial therapy consisted of surgical resection and chemotherapy in all patients and up-front radiotherapy (RT) in 5 patients. Five patients had RT at the time of progression, and 5 received no RT whatever. Kaplan-Meier estimates of overall survival were then calculated. Results: The median follow-up from diagnosis for all patients was 31 months (range, 0.5-165more » months) and for surviving patients was 49 months (range, 10-165). Of the 5 patients who received up-front RT, all were alive without evidence of disease at a median follow-up of 50 months (range, 25-165 months). Only 5 of the 10 patients who did not receive up-front RT were alive at last follow-up. There was a statistically significant difference in overall survival between the patient group that received up-front RT and the group that did not (p = 0.048). In addition, we found a trend toward a statistically significant improvement in overall survival for those patients who received gross total resections (p = 0.10). Conclusions: Up-front RT and gross total resection may confer a survival benefit in patients with sPNET. Local failure was the dominant pattern of recurrence. Efforts should be made to determine patients most likely to have local failure exclusively or as a first recurrence, in order to delay or eliminate craniospinal irradiation.« less

Effects of pinealectomy on the neuroendocrine reproductive system and locomotor activity in male European sea bass, Dicentrarchus labrax.

PubMed

Cowan, Mairi; Paullada-Salmerón, José A; López-Olmeda, José Fernando; Sánchez-Vázquez, Francisco Javier; Muñoz-Cueto, José A

2017-05-01

The seasonally changing photoperiod controls the timing of reproduction in most fish species, however, the transduction of this photoperiodic information to the reproductive axis is still unclear. This study explored the potential role of two candidate neuropeptide systems, gonadotropin-inhibitory hormone (Gnih) and kisspeptin, as mediators between the pineal organ (a principle transducer of photoperiodic information) and reproductive axis in male European sea bass, Dicentrarchus labrax. Two seven-day experiments of pinealectomy (Px) were performed, in March (end of reproductive season) and August (resting season). Effects of Px and season on the brain expression of gnih (sbgnih) and its receptor (sbgnihr), kisspeptins (kiss1, kiss2) and their receptors (kissr2, kissr3) and gonadotropin-releasing hormone (gnrh1, gnrh2, gnrh3) and the main brain receptor (gnrhr-II-2b) genes, plasma melatonin levels and locomotor activity rhythms were examined. Results showed that Px reduced night-time plasma melatonin levels. Gene expression analyses demonstrated a sensitivity of the Gnih system to Px in March, with a reduction in sbgnih in the mid-hindbrain, a region with bilateral connections to the pineal organ. In August, kiss2 levels increased in Px animals but not in controls. Significant differences in expression were observed for diencephalic sbgnih, sbgnihr, kissr3 and tegmental gnrh2 between seasons. Recordings of locomotor activity following surgery revealed a change from light-synchronised to free-running rhythmic behavior. Altogether, the Gnih and Kiss2 sensitivity to Px and seasonal differences observed for Gnih and its receptor, Gnrh2, and the receptor for Kiss2 (Kissr3), suggested they could be mediators involved in the relay between environment and seasonal reproduction. Copyright © 2017 Elsevier Inc. All rights reserved.

Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

PubMed

Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

2016-03-01

Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Distribution of renin activity and angiotensinogen in rat brain. Effects of dietary sodium chloride intake on brain renin.

PubMed Central

Genain, C P; Van Loon, G R; Kotchen, T A

1985-01-01

The purpose of this study was to investigate the biochemistry and the regulation of the brain renin-angiotensin system in the Sprague-Dawley rat. Renin activity and angiotensinogen concentrations (direct and indirect radioimmunoassays) were measured in several brain areas and in neuroendocrine glands. Regional renin activities were measured in separate groups of rats on high and low NaCl diets. Mean tissue renin activities ranged from 2.2 +/- 0.6 to 54.4 +/- 19.7 fmol/mg protein per h (mean of 7 +/- SD), with the highest amounts in pineal, pituitary, and pons-medulla. NaCl depletion increased renin activity in selected regions; based on estimates of residual plasma contamination (despite perfusion of brains with saline), increased renin activity of pineal gland and posterior pituitary was attributed to higher plasma renin. To eliminate contamination by plasma renin, 16-h-nephrectomized rats were also studied. In anephric rats, NaCl depletion increased renin activity by 92% in olfactory bulbs and by 97% in anterior pituitary compared with NaCl-replete state. These elevations could not be accounted for by hyperreninemia. Brain renin activity was low and was unaffected by dietary NaCl in amygdala, hypothalamus, striatum, frontal cortex, and cerebellum. In contrast to renin, highest angiotensinogen concentrations were measured in hypothalamus and cerebellum. Overall, angiotensinogen measurements with the direct and the indirect assays were highly correlated (n = 56, r = 0.96, P less than 0.001). We conclude that (a) NaCl deprivation increases renin in olfactory bulbs and anterior pituitary of the rat, unrelated to contamination by plasma renin; and (b) the existence of angiotensinogen, the precursor of angiotensins, is demonstrated by direct radioimmunoassay throughout the brain and in neuroendocrine glands. PMID:3902894