Pineal gland or epiphysis (in red in back of the brain).

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The pineal gland, also known as the pineal body, conarium or epiphysis cerebri,
is a small endocrine gland in the vertebratebrain. It produces melatonin,
a serotonin derived hormone, which affects the modulation of sleep patterns in both
seasonal andcircadian rhythms.[1][2] Its shape resembles a tiny pine cone (hence its
name), and it is located in the epithalamus, near the center of the brain, between the
two hemispheres, tucked in a groove where the two halves of the thalamus join.
Nearly all vertebrate species possess a pineal gland. The most important exception
is the hagfish, which is often thought of as the most primitive extant vertebrate.
[3]
 Even in the hagfish, however, there may be a "pineal equivalent" structure in the
dorsaldiencephalon.[4] The lancelet Branchiostoma lanceolatum, the nearest existing
relative to vertebrates, also lacks a recognizable pineal gland.
[3]
 The lamprey (considered almost as primitive as the hagfish), however, does
possess one.[3] A few more developed vertebrates, including the alligator, lack pineal
glands because they have been lost over the course of evolution. [5]
The results of various scientific research in evolutionary biology, comparative
neuroanatomy and neurophysiology, have explained the phylogeny of the pineal
gland in different vertebrate species. From the point of view of biological evolution,
the pineal gland represents a kind of atrophied photoreceptor. In the epithalamus of
some species of amphibians and reptiles, it is linked to a vestigial organ, known as
the parietal eye which is also called the third eye.[6]
René Descartes believed the pineal gland to be the "principal seat of the soul"
(a mystical concept). Academic philosophy among his contemporaries considered
the pineal gland as a neuroanatomical structure without special metaphysical
qualities; science studied it as one endocrine gland among many. However, the
pineal gland continues to have an exalted status in the realm ofpseudoscience.[7]

Structure[edit]
The pineal gland is the only midline brain structure that is unpaired (azygous). It
takes its name from its pine-cone shape.[8] The gland is reddish-gray and about the
size of a grain of rice (5–8 mm) in humans. The pineal gland, also called the pineal
body, is part of the epithalamus, and lies between the laterally positioned thalamic
bodies and behind the habenular commissure. It is located in the quadrigeminal
cistern near to the corpora quadrigemina.[9] It is also located behind the third
ventricle and is bathed in cerebrospinal fluid supplied through a small pineal
recess of the third ventricle which projects into the stalk of the gland. [10]
Blood supply[edit]
Unlike most of the mammalian brain, the pineal gland is not isolated from the body by
the blood–brain barrier system;[11] it has profuse blood flow, second only to the
kidney,[12]supplied from the choroidal branches of the posterior cerebral artery.
Innervation[edit]
The pineal gland receives a sympathetic innervation from the superior cervical
ganglion. A parasympathetic innervation from the pterygopalatine and otic ganglia is
also present.[13] Further, some nerve fibers penetrate into the pineal gland via the

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pineal stalk (central innervation). Also, neurons in the trigeminal ganglion innervate
the gland with nerve fibers containing the neuropeptide PACAP.
Histology[edit]
In some parts of the brain and in particular the pineal gland, there are calcium
structures, the number of which increases with age, 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.[15] In 2002, deposits of the calcite form of calcium carbonate were
described.[16] Calcium and phosphorus[17]deposits in the pineal gland have been
linked with aging.
Development[edit]
The human pineal gland grows in size until about 1–2 years of age, remaining stable
thereafter,[18][19] although its weight increases gradually from puberty onwards. [20]
[21]
 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.[citation needed]

Function[edit]
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.[22][23] Photosensitive cells in the retina detect light and directly signal
the suprachiasmatic nucleus (SCN), entraining its rhythm to the 24-hour cycle in
nature. Fibers project from the SCN to theparaventricular 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-
carbolines.[24]
Regulation of the pituitary gland[edit]
Studies on rodents suggest that the pineal gland influences the pituitary gland's
secretion of the sex hormones follicle-stimulating hormone (FSH), and luteinizing
hormone (LH). In a study by Motta, Fraschini, and Martini (1967),
a pinealectomy was performed on rodents. No change in pituitary weight was
observed, however there was an increase in the concentration of FSH and LH within
the gland. In this same study, administration of melatonin did not return the
concentrations of FSH to normal levels, suggesting that the pineal gland influences
the pituitary glands secretion of FSH and LH through some other transmitting
molecule.[25]
Drug metabolism[edit]
Studies on rodents suggest that the pineal gland may influence the actions
of recreational drugs, such as cocaine,[26] and antidepressants, such as fluoxetine
(Prozac),[27] and that its hormone melatonin can protect against neurodegeneration.[28]

Clinical significance[edit]
Calcification[edit]

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Calcification of the pineal gland is typical (1% of study participants) in young adults,
and has been observed in children as young as two years of age. [29] The calcified
gland is often seen in skull X-Rays.[29] Calcification rates vary widely by country and
correlate with an increase in age, with calcification occurring in an estimated 40% of
Americans by their 17th year.[29] Calcification of the pineal gland is largely associated
with corpora arenacea also known as "brain sand".
It seems that 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. [30]
Some studies show that the degree of pineal gland calcification is significantly higher
in patients with Alzheimer's disease vs. other types of dementia.[31]
Pineal gland calcification may also contribute to the pathogenesis of Alzheimer's
disease and may reflect an absence of crystallization inhibitors. [31]
Calcium, phosphorus,[17] and fluoride deposits in the pineal gland have been
correlated with aging, showing that, as the brain ages, more deposits collect. [32]
Tumours[edit]
Tumours of the pineal gland are called pinealomas. These tumours are rare and 50%
to 70% are germinomas that arise from sequestered embryonic germ
cells. Histologicallythey are similar to testicular seminomas and
ovarian dysgerminomas.[33]
A pineal tumour can compress the superior colliculi and pretectal area of the
dorsal midbrain, producing Parinaud's syndrome. Pineal tumours also can cause
compression of thecerebral aqueduct, resulting in a
noncommunicating hydrocephalus. Other manifestations are the consequence of
their pressure effects and consist of visual disturbances,headache, mental
deterioration, and sometimes dementia-like behaviour. [34]
These neoplasms are divided into three categories, pineoblastomas, pineocytomas,
and mixed tumours, based on their level of differentiation, which, in turn, correlates
with their neoplastic aggressiveness.[35] The clinical course of patients with
pineocytomas is prolonged, averaging up to several years. [36] The position of these
tumours makes them very difficult or impossible to remove surgically.

Other animals[edit]
Pinealocytes in many non-mammalian vertebrates have a strong resemblance to
the photoreceptor cells of the eye. Some evolutionary biologists believe that the
vertebrate pineal cells possess a common evolutionary ancestor with retinal cells.[37]
Pineal cytostructure seems to have evolutionary similarities to the retinal cells of
chordates.[37] Modern birds and reptiles have been found to express
the phototransducingpigment melanopsin in the pineal gland. Avian pineal glands are
believed to act like the SCN in mammals.[38]
In some vertebrates, exposure to light can set off a chain reaction of enzymatic
events within the pineal gland that regulate circadian rhythms.[39] Some early
vertebrate fossil skulls have a pineal foramen (opening). This correlates with the
physiology of the modern "living fossils," the lampreys and the tuatara, and some
other vertebrates that have aparietal eye, which, in some of them, is photosensitive.
The parietal eye represents evolution's earlier approach to photoreception. [40] The
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structures of the pineal 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." [40]
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.[41]
In humans and other mammals, the light signals necessary to set circadian rhythms
are sent from the eye through the retinohypothalamic system to the suprachiasmatic
nuclei(SCN) and the pineal gland.

Society and culture[edit]

Diagram of the operation of the pineal gland for Descartes in the Treaty of Man
(figure published in the edition of 1664)
Seventeenth-century philosopher and scientist René Descartes was highly interested
in anatomy and physiology. He discussed the pineal gland both in his first book,
the Treatise of Man (written before 1637, but only published posthumously
1662/1664), and in his last book,The Passions of the Soul (1649) and he regarded it
as "the principal seat of the soul and the place in which all our thoughts are
formed."[7]In the Treatise of Man, Descartes did not describe man, but a kind of
conceptual models of man, namely creatures, created by God, which consist of two
ingredients, a body and a soul.[7][42] In the Passions, Descartes begins by splitting
man up into a body and a soul and emphasized that the soul is joined to the whole
body by "a certain very small gland situated in the middle of the brain's substance
and suspended above the passage through which the spirits in the brain's anterior
cavities communicate with those in its posterior cavities".Descartes attached
significance to the gland because he believed it to be the only section of the brain to
exist 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 arteries. The pineal
gland played an important role in Descartes' account because it was involved in
sensation, imagination, memory and the causation of bodily movements. But most
ofDescartes' basic anatomical and physiological assumptions were totally mistaken,
not only by our standards, but also in light of what was already known in his time. [7]
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." [43]
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.[44] This conceptual device is explicit in his surrealist
texts, The Jesuve and The Pineal Eye.[45]
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Numerous spiritual philosophies contain the notion of an inner third eye that is related
to the Ajna chakra and also to the pineal gland. These are attributed significance in
mystical awakening or enlightenment, clairvoyant perception, and higher states of
consciousness. This idea occurs historically in Asia[dubious  –  discuss], as well as in
contemporary theories connecting to theosophy, and neo-pagan religions, as well
as New Age spiritual philosophies. It was particularly expounded by Madame
Blavatsky in 1888 and gained a growing popularity in the West. [46]
Author and researcher Rick Strassman has theorised that the pineal gland is capable
of producing the hallucinogen N,N-dimethyltryptamine (DMT) under certain
circumstances, calling the drug "the spirit molecule".
The current academic philosophy considered the pineal gland as a neuroanatomical
structure without special metaphysical qualities. Science studied it as one endocrine
gland among many. However, the pineal gland continues to have an exalted status in
pseudoscience.[7]

History[edit]
The secretory activity of the pineal gland is only partially understood. Its location
deep in the brain suggested to philosophers throughout history that it possesses
particular importance. This combination led to its being regarded as a "mystery"
gland with mystical, metaphysical, and occult theories surrounding its perceived
functions.
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
professorAaron 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 melatoninin 1958.[47] 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.[48]

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