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==Location==
The pineal gland is reddish-gray and about the size of a grain of rice (5–8 mm) in humans, located just rostro-dorsal to the [[superior colliculus]] and behind and beneath the [[stria medullaris]], between the laterally positioned [[thalamic bodies]]. It is part of the [[epithalamus]].
The pineal gland is a midline structure shaped like a pine cone,<ref>{{cite web|last=Bowen|first=R.|title=The Pineal Gland and Melatonin|url=http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/pineal.html|accessdate=14 October 2011}}</ref> and is often seen in plain [[human skull|skull]] [[X-ray]]s, as it is often [[calcification|calcified]];<ref name=rsna>{{cite web|last=Zimmerman|first=Robert A|title=Age-Related Incidence of Pineal Calcification Detected by Computed Tomography|url=http://radiology.rsna.org/content/142/3/659.full.pdf|publisher=Radiological Society of North America|accessdate=21 June 2012}}</ref> calcification has been shown in one small study to correlate with the accumulation of fluoride. <ref name=ICNR>{{cite web|last=Luke|first=Jennifer |title=Fluoride Deposition in the Aged Human Pineal Gland|url=http://www.icnr.com/articles/fluoride-deposition.html|publisher=School of Biological Sciences, University of Surrey, Guildford, UK
Department of Obstetrics and Gynaecology, The Royal London Hospital |accessdate=09 August 2012}}</ref>
==Structure and composition==
[[File:Pineal.jpg|thumb|Pineal gland parenchyma with calcifications.]]
[[File:Pineal gland - very high mag.jpg|thumb|150px|[[Micrograph]] of a normal pineal gland – very high magnification.]]
[[File:Pineal gland - intermed mag.jpg|thumb|150px|[[Micrograph]] of a normal pineal gland – intermediate magnification.]]
The pineal body consists in humans of a lobular [[parenchyma]] of [[pinealocytes]] surrounded by [[connective tissue]] spaces. The gland's surface is covered by a [[pial]] capsule.
The pineal gland consists mainly of pinealocytes, but four other [[cell (biology)|cell]] types have been identified. As it is quite cellular (in relation to the cortex and white matter) it may be mistaken for a [[neoplasm]].<ref>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy—part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |date=November 2006 |pmid=17076524 |doi=10.1043/1543-2165(2006)130[1630:AAATTB]2.0.CO;2 |year=2006}}</ref>
{| class="wikitable" border="1"
|-
! Cell type !! Description
|-
| [[Pinealocyte]]s || The pinealocytes consist of a cell body with 4–6 processes emerging. They produce and secrete [[melatonin]]. The pinealocytes can be stained by special silver impregnation methods. Their cytoplasm is lightly basophilic. With special stains, pinealocytes exhibit lengthy, branched cytoplasmic processes which extend to the connective septa and its blood vessels.
|-
| [[Interstitial cell]]s || Interstitial cells are located between the pinealocytes. They have elongated nuclei and a cytoplasm which is stained darker than that of the pinealocytes.
|-
| [[Perivascular]] [[phagocyte]] || Many capillaries are present in the gland, and perivascular phagocytes are located close to these blood vessels. The perivascular phagocytes are antigen presenting cells.
|-
| pineal [[neuron]]s || In higher vertebrates neurons are located in the pineal gland. However, these are not present in rodents.
|-
| [[peptide]]rgic neuron-like cells || In some species, neuronal-like peptidergic cells are present. These cells might have a paracrine regulatory function.
|}
The pineal gland receives a [[sympathetic nervous system|sympathetic]] innervation from the [[superior cervical ganglion]]. However, a [[parasympathetic]] innervation from the [[sphenopalatine]] and [[otic ganglion|otic ganglia]] is also present. Further, some nerve fibers penetrate into the pineal gland via the pineal stalk (central innervation). Finally, neurons in the [[trigeminal ganglion]] innervate the gland with nerve fibers containing the [[neuropeptide]], [[PACAP]]. Human follicles contain a variable quantity of gritty material, called [[corpora arenacea]] (or "acervuli," or "brain sand"). Chemical analysis shows that they are composed of [[calcium phosphate]], [[calcium carbonate]], [[magnesium phosphate]], and [[ammonium phosphate]].<ref>{{cite journal |author=Bocchi G, Valdre G |title=Physical, chemical, and mineralogical characterization of carbonate-hydroxyapatite concretions of the human pineal gland |journal=J Inorg Biochem |volume=49 |issue=3 |pages=209–20 |year=1993 |pmid=8381851 |doi=10.1016/0162-0134(93)80006-U}}</ref> In 2002, deposits of the [[calcite]] form of calcium carbonate were described.<ref>{{cite journal |author=Baconnier S, Lang S, Polomska M, Hilczer B, Berkovic G, Meshulam G |title=Calcite microcrystals in the pineal gland of the human brain: first physical and chemical studies |journal=Bioelectromagnetics |volume=23 |issue=7 |pages=488–95 |year=2002 |pmid=12224052 |doi=10.1002/bem.10053}}</ref> Calcium, phosphorus<ref>{{cite web |url= http://www.ingentaconnect.com/content/hum/bter/2007/00000119/00000002/art00004 |title=IngentaConnect High Accumulation of Calcium and Phosphorus in the Pineal Bodies |publisher=Ingentaconnect.com |date= 2006-06-16 |accessdate=2009-07-06}}</ref> deposits in the pineal gland have been linked with aging.
==Miscellaneous anatomy==
[[Pinealocyte]]s in many non-mammalian [[vertebrate]]s have a strong resemblance to the [[photoreceptor cell]]s of the [[eye]]. Some evolutionary biologists believe that the vertebrate pineal cells share a common [[evolution]]ary ancestor with retinal cells.<ref name="author=klein d264">{{cite journal |author=Klein D |title=The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland—a tale of conflict and resolution |journal=J Biol Rhythms |volume=19 |issue=4 |pages=264–79 |year=2004 |pmid=15245646 |doi=10.1177/0748730404267340}}</ref>
In some vertebrates, exposure to light can set off a chain reaction of enzymatic events within the pineal gland that regulate [[circadian rhythm]]s.<ref>{{cite journal | pmid = 6015532 | volume=155 | issue=759 | title=Visual pathway mediating pineal response to environmental light | year=1967 | month=January | journal=Science | pages=220–3 | author=Moore RY, Heller A, Wurtman RJ, Axelrod J | doi = 10.1126/science.155.3759.220}}</ref> Some early vertebrate fossil skulls have a pineal [[foramina of the skull|foramen]] (opening). This correlates with the physiology of the modern "[[living fossil]]s," the [[lamprey]] and the [[tuatara]], and some other vertebrates that have a [[parietal eye|parietal organ]] or "third eye," which, in some of them, is photosensitive. The third eye represents evolution's earlier approach to photoreception.<ref name="Schwab">{{cite journal |last=Schwab |first=I.R. |coauthors=O'Connor, G.R. |date=March 2005 |title=The lonely eye |journal=British Journal of Ophthalmology |volume=89 |issue=3 |page=256 |doi=10.1136/bjo.2004.059105 |format=Full text |pmc=1772576 |pmid=15751188}}</ref> The structures of the third eye in the tuatara are analogous to the cornea, lens and retina, though the latter resembles that of an octopus rather than a vertebrate retina. The asymmetrical whole consists of the "eye" to the left and the pineal sac to the right. "In animals that have lost the parietal eye, including mammals, the pineal sac is retained and condensed into the form of the pineal gland."<ref name="Schwab"/>
Unlike much of the rest of the mammalian brain, the pineal gland is not isolated from the body by the [[blood–brain barrier]] system;<ref>{{cite book |last=Pritchard |first=Thomas C. |coauthors=Alloway, Kevin Douglas |title=Medical Neuroscience |url=http://books.google.com/?id=m7Y80PcFHtsC&printsec=frontcover#PPA76,M1 |format=Google books preview |accessdate=2009-02-08 |year=1999 |publisher=Hayes Barton Press |isbn= 1-889325-29-5 |pages=76–77}}</ref> it has profuse blood flow, second only to the kidney.
Fossils seldom preserve soft anatomy. The brain of the Russian ''[[Melovatka]]'' bird, about 90 million years old, is an exception, and it shows a larger-than-expected parietal eye and pineal gland.<ref>{{cite journal |last=Kurochkin |first=Evgeny N. |coauthors=Gareth J. Dyke, Sergei V. Saveliev, Evgeny M. Pervushov, Evgeny V. Popov |date=June 2007 |title=A fossil brain from the Cretaceous of European Russia and avian sensory evolution |journal=Biology Letters |volume=3 |issue=3 |pages=309–313 |publisher=The Royal Society |pmid=17426009 |doi=10.1098/rsbl.2006.0617 |format=Full text |pmc=2390680}}</ref>
In humans and other mammals, the light signals necessary to set circadian rhythms are sent from the eye through the [[retinohypothalamic tract|retinohypothalamic]] system to the [[suprachiasmatic nuclei]] (SCN) and the pineal.
==Function==
The pineal gland was originally believed to be a "[[vestigial]] remnant" of a larger organ. In 1917 it was known that extract of cow pineals lightened frog skin. Dermatology professor [[Aaron B. Lerner]] and colleagues at [[Yale University]], hoping that a substance from the pineal might be useful in treating skin diseases, isolated and named the hormone [[melatonin]] in 1958.<ref>{{cite journal |author=Lerner AB, Case JD, Takahashi Y |title=Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands |journal=J Biol Chem |volume=235 |pages=1992–7 |year=1960 |pmid=14415935}}</ref> The substance did not prove to be helpful as intended, but its discovery helped solve several mysteries such as why removing the rat's pineal accelerated ovary growth, why keeping rats in constant light decreased the weight of their pineals, and why pinealectomy and constant light affect ovary growth to an equal extent; this knowledge gave a boost to the then new field of [[chronobiology]].<ref name="Coates">{{cite book |last=Coates |first=Paul M. |others=Marc R. Blackman, Gordon M. Cragg, Mark Levine, Joel Moss, Jeffrey D. White |title=Encyclopedia of Dietary Supplements |url=http://books.google.com/?id=Sfmc-fRCj10C&pg=PA457&lpg=PA457&dq=Lerner+melatonin+history |accessdate=2009-03-31 |year=2005 |publisher=CRC Press |isbn=0-8247-5504-9 |page=457}}</ref>
[[Melatonin]] is N-acetyl-5-methoxy-tryptamine, a derivative of the [[amino acid]] [[tryptophan]], which also has other functions in the [[central nervous system]]. The production of melatonin by the pineal gland is stimulated by darkness and inhibited by light.<ref>{{cite journal |author=Axelrod J |title=The pineal gland |journal=Endeavour |volume=29 |issue=108 |pages=144–8 |year=1970 |pmid=4195878}}</ref> [[Photosensitive ganglion cell|Photosensitive cells]] in the retina detect light and directly signal the SCN, entraining its rhythm to the 24-hour cycle in nature. Fibers project from the SCN to the paraventricular nuclei (PVN), which relay the circadian signals to the [[spinal cord]] and out via the sympathetic system to [[superior cervical ganglia]] (SCG), and from there into the pineal gland.
The compound [[pinoline]] is also produced in the pineal gland; it is one of the [[beta-carboline]]s.{{Citation needed|date=September 2011}}
The human pineal gland grows in size until about 1–2 years of age, remaining stable thereafter,<ref>Lack of pineal growth during childhood. Schmidt F, Penka B, Trauner M, Reinsperger L, Ranner G, Ebner F, Waldhauser F. J Clin Endocrinol Metab. 1995 Apr;80(4):1221–5.</ref><ref>Development of the pineal gland: measurement with MR. Sumida M, Barkovich AJ, Newton TH. AJNR Am J Neuroradiol. 1996 Feb;17(2):233–6.</ref> although its weight increases gradually from puberty onwards.<ref>Tapp E, Huxley M. The weight and degree of calcification of the pineal gland. J Pathol 1971;105:31–39</ref><ref>Tapp E, Huxley M. The histological appearance of the human pineal gland from puberty to old age. J Pathol 1972;108:137–144</ref> The abundant melatonin levels in children are believed to inhibit sexual development, and pineal tumors have been linked with [[precocious puberty]]. When puberty arrives, melatonin production is reduced.
[[Calcification]] of the pineal gland is typical in adults, and has been observed in children as young as 2. Calcification rates vary widely by country and tend to increase by age, with calcification occurring in an estimated 40% of Americans by their 17th year.<ref name=rsna />
Apparently the internal secretions of the pineal gland inhibit the development of the reproductive glands, because in cases where it is severely damaged in children, the result is accelerated development of the sexual organs and the skeleton.<ref name="Gray">{{Cite web|url=http://www.theodora.com/anatomy/the_pineal_body.html |title= The Pineal Body
|work=Human Anatomy (Gray's Anatomy) |accessdate=2011-09-07}}</ref> In animals, the pineal gland appears to play a major role in sexual development, [[hibernation]], metabolism, and seasonal breeding.<ref>Strassman</ref>
Pineal [[cytostructure]] seems to have evolutionary similarities to the retinal cells of chordates.<ref name="author=klein d264"/> Modern [[bird]]s and [[reptile]]s have been found to express the [[phototransducing]] [[pigment]] [[melanopsin]] in the pineal gland. Avian pineal glands are believed to act like the [[Suprachiasmatic nucleus|SCN]] in [[mammal]]s.<ref>{{cite journal |author=Natesan A, Geetha L, Zatz M |title=Rhythm and soul in the avian pineal |journal=Cell Tissue Res |volume=309 |issue=1 |pages=35–45 |year=2002 |pmid=12111535 |doi=10.1007/s00441-002-0571-6}}</ref>
Studies on rodents suggest that the pineal gland may influence the actions of recreational drugs, such as cocaine,<ref>{{cite journal |author=Uz T, Akhisaroglu M, Ahmed R, Manev H |title=The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice |journal=Neuropsychopharmacology |volume=28 |issue=12 |pages=2117–23 |year=2003 |pmid=12865893 |doi= 10.1038/sj.npp.1300254}}</ref> and [[antidepressant]]s, such as fluoxetine (Prozac),<ref>{{cite journal |author=Uz T, Dimitrijevic N, Akhisaroglu M, Imbesi M, Kurtuncu M, Manev H |title=The pineal gland and anxiogenic-like action of fluoxetine in mice |journal=Neuroreport |volume=15 |issue=4 |pages=691–4 |year=2004 |pmid=15094477 |doi=10.1097/00001756-200403220-00023}}</ref> and its hormone melatonin can protect against [[neurodegeneration]].<ref>{{cite journal |author=Manev H, Uz T, Kharlamov A, Joo J |title=Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats |journal=FASEB J |volume=10 |issue=13 |pages=1546–51 |year=1996 |pmid=8940301}}</ref>
===Conjecture===
Dr. [[Rick Strassman]], while conducting research on the [[psychedelic drug|psychedelic]] [[dimethyltryptamine]] (DMT) in the 1990s at the [[University of New Mexico]], advanced the controversial hypothesis that a massive release of DMT from the pineal gland prior to death or near death was the cause of the [[near death experience]] (NDE) phenomenon. Several of his test subjects reported [[Near-death experience|NDE]]-like audio or visual hallucinations. His explanation for this was the possible lack of panic involved in the clinical setting and possible dosage differences between those administered and those encountered in actual NDE cases. Several subjects also reported contact with 'other beings', alien like, insectoid or reptilian in nature, in highly advanced technological environments<ref name="strassman">{{cite book |title=DMT: The Spirit Molecule. A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences |last=Strassman |first=Rick J. |authorlink=Rick Strassman |year=2001 |publisher=Park Street |location=Rochester, Vt |isbn=978-0-89281-927-0}} ({{cite web | url=http://rickstrassman.com/index.php?option=com_content&view=article&id=61&Itemid=60 | title=Chapter summaries | accessdate=27 February 2012}})</ref> where the subjects were 'carried,' 'probed,' 'tested,' 'manipulated,' 'dismembered,' 'taught,' 'loved,' and even 'raped' by these 'beings' (one could note the strong similarities of these bodily tests/invasions in other psychedelic experiences throughout time, outlined in Graham Hancock's "Supernatural"<ref>{{cite book |title=Supernatural: Meetings with the Ancient Teachers of Mankind |last=Hancock |first=Graham |authorlink=Graham_Hancock |year=2005 |publisher=Century |location=London |isbn=978-1-84413-681-0}}</ref>). Basing his reasoning on his belief that all the enzymatic material needed to produce DMT is found in the pineal gland (see [[Dimethyltryptamine#Evidence_in_mammals|evidence in mammals]]), and moreover in substantially greater concentrations than in any other part of the body, Strassman (<ref name="strassman"/> p. 69) has speculated that DMT is made in the pineal gland.
==Pathology==
All [[tumors]] involving the pineal gland are rare; most (50% to 70%) arise from sequestered embryonic [[germ cells]]. They most commonly take the form of so-called ''germinomas'', resembling testicular seminoma or ovarian dysegerminoma. Other lines of germ cell differentiation include embryonal carcinomas; choriocarcinomas; mixtures of germinom, embryonal carcinoma, and choriocarcinoma; and, uncommonly, typical teratomas (usually benign). Whether to characterize these germ cell neoplasms as pinealomas is still a subject of debate, but most ''pinealophiles'' favor restricting the terms ''pinealoma'' to neoplasms arising from the pineocytes.
A pineal tumor can compress the [[Superior colliculus|superior colliculi]] and [[pretectal area]] of the dorsal [[midbrain]], producing [[Parinaud's syndrome]]. Pineal tumors also can cause compression of the [[cerebral aqueduct]], resulting in a noncommunicating [[hydrocephalus]].
===Pinelomas===
These [[neoplasms]] are divided into two categories, pineoblastomas and [[pineocytomas]],{{Citation needed|date=September 2011}} based on their level of differentiation, which in turn, correlates with their neoplastic aggressiveness. The clinical course of patients with pineocytomas is prolonged, averaging 7 years.{{Citation needed|date=September 2011}} The manifestations are the consequence of their pressure effects and consist of visual disturbances, [[headache]], mental deterioration, and sometimes dementia-like behaviour.{{Citation needed|date=September 2011}} The lesions being located where they are, it is understandable that successful excision is at best difficult.
==Metaphysics and philosophy==
The secretory activity of the pineal gland is only partially understood. Historically, its location deep in the brain suggested to philosophers that it possessed particular importance. This combination led to its being a "mystery" gland with myth, superstition and [[occult]] theories surrounding its perceived functions.
[[René Descartes]], who dedicated much time to the study of the pineal gland, called it the "principal seat of the [[Soul (spirit)|soul]]."<ref name="Descartes and the Pineal Gland">[http://plato.stanford.edu/entries/pineal-gland/ Descartes and the Pineal Gland] ([[Stanford Encyclopedia of Philosophy]])</ref> He believed that it was the point of connection between the intellect and the body.<ref>Descartes R. "The Passions of the Soul" excerpted from "Philosophy of the Mind," Chalmers, D. New York: Oxford University Press, Inc.; 2002. ISBN 978-0-19-514581-6</ref> Descartes attached significance to the gland because he believed it to be the only section of the brain which existed as a single part, rather than one half of a pair. He argued that because a person can never have "more than one thought at a time," external stimuli must be united within the brain before being considered by the soul, and he considered the pineal gland to be situated in "the most suitable possible place for this purpose," located centrally in the brain and surrounded by branches of the [[carotid artery|carotid arteries]].<ref name="Descartes and the Pineal Gland"/>
[[Baruch de Spinoza]] criticized Descartes' viewpoint for neither following from self-evident premises nor being "clearly and distinctly perceived" (Descartes having previously asserted that he could not draw conclusions of this sort), and questioned what Descartes meant by talking of "the union of the mind and the body."<ref>http://en.wikisource.org/wiki/Ethics_%28Spinoza%29/Part_5</ref>
The notion of a "pineal-eye" is central to the philosophy of the French writer [[Georges Bataille]], which is analyzed at length by literary scholar Denis Hollier in his study ''Against Architecture''. In this work Hollier discusses how Bataille uses the concept of a "pineal-eye" as a reference to a blind-spot in Western rationality, and an organ of excess and delirium.<ref>Hollier, D, ''Against Architecture: The Writings of Georges Bataille'', trans. Betsy Wing, MIT, 1989.</ref> This conceptual device is explicit in his surrealist texts, ''The Jesuve'' and ''The Pineal Eye''.<ref>Bataille, G, ''Visions of Excess: Selected Writings, 1927–1939 (Theory and History of Literature, Vol 14)'', trans. Allan Stoekl et al., Manchester University Press, 1985</ref>
The notion of an inner [[third eye]] (attributed mystical significance) also occurs in ancient, central and east Asian, and new age philosophies.
Generally, all of these hypotheses lack scientific support.
==Additional images==
The pineal body is labeled in these images.
<gallery>
Image:Gray715.png|Mesal aspect of a brain sectioned in the median sagittal plane.
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