The pineal gland is present in almost all vertebrates, but is absent inprotochordates, in which there is a simple pineal homologue. Thehagfish, archaic vertebrates, lack a pineal gland.[7] In some species of amphibians and reptiles, the gland is linked to a light-sensing organ, variously called theparietal eye, the pineal eye or the third eye.[8] Reconstruction of the biological evolution pattern suggests that the pineal gland was originally a kind of atrophiedphotoreceptor that developed into a neuroendocrine organ.[9][10]
Galen in the 2nd centuryC.E. could not find any functional role and regarded the gland as a structural support for the brain tissue. He gave the namekonario, meaning cone or pinecone, which during theRenaissance was translated into Latin aspinealis. The 17th-century philosopherRené Descartes regarded the gland as the primary locus of mind-body interaction, describing it as the "principal seat of the soul".
The pineal gland is a pine cone-shaped (hence the name), unpaired midline brain structure.[3][11] It is reddish-gray in colour and about the size of a grain of rice (5–8 mm) in humans. It forms part of theepithalamus.[1] It is attached to the rest of the brain by a pineal stalk.[12] The ventral lamina of the pineal stalk is continuous with theposterior commissure, and its dorsal lamina with thehabenular commissure.[12]
Unlike most of the mammalian brain, the pineal gland is not isolated from the body by theblood–brain barrier system;[14] it has profuse blood flow, second only to thekidney,[15] supplied from the choroidal branches of theposterior cerebral artery.
The canonical neural pathway regulating pineal melatonin production begins in the eye with the intrinsically photosensitive ganglion cells of the retina which project inhibitory GABAergic efferents to theparaventricular nucleus of hypothalamus via theretinohypothalamic tract. The paraventricular nucleus in turn projects to the superior cervical ganglia, which finally projects to the pineal gland. Darkness thus leads to disinhibition of the paraventricular nucleus, leading it to activate pineal gland melatonin production by way of the superior cervical ganglia.[19]
Pineal gland parenchyma with calcificationsMicrograph of a normal pineal gland – very high magnificationMicrograph of a normal pineal gland – intermediate magnification
The pineal gland consists mainly ofpinealocytes, but four othercell types have been identified. As it is quite cellular (in relation to the cortex and white matter), it may be mistaken for aneoplasm.[20]
The pinealocytes consist of a cell body with 4–6 processes emerging. They produce and secretemelatonin. The pinealocytes can be stained by special silver impregnation methods. Their cytoplasm is lightlybasophilic. With special stains, pinealocytes exhibit lengthy, branched cytoplasmic processes that extend to the connective septa and its blood vessels.
Interstitial cells are located between the pinealocytes. They have elongated nuclei and a cytoplasm that is stained darker than that of the pinealocytes.
Many capillaries are present in the gland, and perivascular phagocytes are located close to these blood vessels. The perivascular phagocytes areantigen presenting cells.
The human pineal gland grows in size until about 1–2 years of age, remaining stable thereafter,[21][22] although its weight increases gradually from puberty onwards.[23][24] The abundant melatonin levels in children are believed to inhibit sexual development, and pineal tumors have been linked withprecocious puberty. When puberty arrives, melatonin production is reduced.[25]
In thezebrafish the pineal gland does not straddle the midline, but shows a left-sided bias. Inhumans, functional cerebral dominance is accompanied by subtle anatomical asymmetry.[26][27][28]
One function of the pineal gland is to producemelatonin. Melatonin has various functions in thecentral nervous system, the most important of which is to help modulate sleep patterns. Melatonin production is stimulated by darkness and inhibited by light.[29][30]Light sensitive nerve cells in the retina detect light and send this signal to thesuprachiasmatic nucleus (SCN), synchronizing the SCN to the day-night cycle. Nerve fibers then relay the daylight information from the SCN to theparaventricular nuclei, then to thespinal cord and via the sympathetic system tosuperior cervical ganglia, and from there into the pineal gland.
The compoundpinoline is also claimed to be produced in the pineal gland; it is one of thebeta-carbolines.[31] This claim is subject to some controversy.[citation needed]
Studies on rodents suggest that the pineal gland influences thepituitary gland's secretion of the sex hormones,follicle-stimulating hormone (FSH), andluteinizing hormone (LH).Pinealectomy performed on rodents produced no change in pituitary weight, but caused an increase in the concentration of FSH and LH within the gland.[32] Administration ofmelatonin did not return the concentrations of FSH to normal levels, suggesting that the pineal gland influences pituitary gland secretion of FSH and LH through an undescribed transmitting molecule.[32]
Calcification of the pineal gland is typical in young adults, and has been observed in children as young as two years of age.[35] The internal secretions of the pineal gland are known to inhibit the development of the reproductive glands because when it is severely damaged in children, development of the sexual organs and the skeleton are accelerated.[36] Pineal gland calcification is detrimental to its ability to synthesize melatonin[37][38] and scientific literature presents inconclusive findings on whether it causes sleep problems.[39][40]
The calcified gland is often seen in skullX-rays.[35] Calcification rates vary widely by country and correlate with an increase in age, with calcification occurring in an estimated 40% of Americans by age seventeen.[35] Calcification of the pineal gland is associated withcorpora arenacea, also known as "brain sand".
A pineal tumor can compress thesuperior colliculi andpretectal area of the dorsalmidbrain, producingParinaud's syndrome. Pineal tumors also can cause compression of thecerebral aqueduct, resulting in a noncommunicatinghydrocephalus. Other manifestations are the consequence of their pressure effects and consist of visual disturbances,headache, mental deterioration, and sometimes dementia-like behaviour.[42]
Theseneoplasms are divided into three categories: pineoblastomas,pineocytomas, and mixed tumors, based on their level of differentiation, which, in turn, correlates with their neoplastic aggressiveness.[43] The clinical course of patients with pineocytomas is prolonged, averaging up to several years.[44] The position of these tumors makes them difficult to remove surgically.
The morphology of the pineal gland differs markedly in different pathological conditions. For instance, it is known that its volume is reduced in bothobese patients and those with primaryinsomnia.[45]
Nearly all vertebrate species possess a pineal gland. The most important exception is a primitive vertebrate, thehagfish. Even in the hagfish, however, there may be a "pineal equivalent" structure in the dorsaldiencephalon.[7] A few more complex vertebrates have lost pineal glands over the course of their evolution.[46] Thelamprey (another primitive vertebrate), however, does possess one.[47] ThelanceletBranchiostoma lanceolatum, an early chordate which is a close relative to vertebrates, also lacks a recognizable pineal gland.[47] Protochordates in general do not have the distinct structure as an organ, but they have a mass of photoreceptor cells calledlamellar body, which is regarded as a pineal homologue.[48][49]
The results of various scientific research in evolutionary biology, comparative neuroanatomy and neurophysiology have explained the evolutionary history (phylogeny) of the pineal gland in different vertebrate species. From the point of view of biological evolution, the pineal gland is a kind of atrophiedphotoreceptor[citation needed]. In theepithalamus of some species of amphibians and reptiles, it is linked to a light-sensing organ, known as theparietal eye, which is also called the pineal eye orthird eye.[8] It is likely that thecommon ancestor of allvertebrates had a pair of photosensory organs on the top of its head, similar to the arrangement in modernlampreys.[50] In many lower vertebrates (such as species of fish, amphibians and lizards), the pineal gland is associated withparietal or pineal eye. In these animals, the parietal eye acts as a photoreceptor, and hence are also known as the third eye, and they can be seen on top of the head in some species.[51] Some extinctDevonian fishes have two parietal foramina in their skulls,[52][53] suggesting an ancestral bilaterality of parietal eyes. The parietal eye and the pineal gland of livingtetrapods are probably the descendants of the left and right parts of this organ, respectively.[54]
Duringembryonic development, theparietal eye and the pineal organ of modernlizards[55] andtuataras[56] form together from a pocket formed in the brainectoderm. The loss of parietal eyes in many living tetrapods is supported by developmental formation of a paired structure that subsequently fuses into a single pineal gland in developing embryos of turtles, snakes, birds, and mammals.[57]
The pineal organs of mammals fall into one of three categories based on shape. Rodents have more structurally complex pineal glands than other mammals.[58]
All amphibians have a pineal organ, but some frogs and toads also have what is called a "frontal organ", which is essentially a parietal eye.[61]
Pinealocytes in many non-mammalianvertebrates have a strong resemblance to thephotoreceptor cells of theeye. Evidence from morphology and developmental biology suggests that pineal cells possess a commonevolutionary ancestor with retinal cells.[62]
Pinealcytostructure seems to have evolutionary similarities to the retinal cells of the lateral eyes.[62] Modernbirds andreptiles express thephototransducingpigmentmelanopsin in the pineal gland. Avian pineal glands are thought to act like thesuprachiasmatic nucleus inmammals.[63] The structure of the pineal eye in modern lizards and tuatara is analogous to the cornea, lens, and retina of the lateral eyes of vertebrates.[57]
In most vertebrates, exposure to light sets off a chain reaction of enzymatic events within the pineal gland that regulatescircadian rhythms.[64] In humans and other mammals, the light signals necessary to set circadian rhythms are sent from the eye through theretinohypothalamic system to thesuprachiasmatic nuclei (SCN) and the pineal gland.
The fossilized skulls of many extinct vertebrates have a pinealforamen (opening), which in some cases is larger than that of any living vertebrate.[65] Although fossils seldom preserve deep-brain soft anatomy, the brain of the Russian fossil birdCerebavis cenomanica from Melovatka, about 90 million years old, shows a relatively large parietal eye and pineal gland.[66]
Diagram of the operation of the pineal gland forDescartes in theTreatise of Man (figure published in the edition of 1664)
The secretory activity of the pineal gland is only partially understood. Its location deep in the brain suggested to philosophers throughout history that it possessed particular importance. This combination led to its being regarded as a "mystery" gland withmystical,metaphysical, andoccult theories surrounding its perceived functions.[67]
The earliest recorded description of the pineal gland is from the Greek physicianGalen in the 2nd century C.E.[68] According to Galen,Herophilus (325–280 B.C.E.) had already considered the structure as a kind of valve that partitioned the brain chambers, particularly for the flow of vital spirits (pneuma).[69] Specifically, Herophilus believed that the structure was atap that controlled the movement of vital spirits from the middle (now identified as thethird) ventricle to the one in the parencephalis (fourth ventricle).[70][71][72]
Galen described the pineal gland inDe usu partium corporis humani, libri VII (On the Usefulness of Parts of the Body, Part 8) andDe anatomicis administrationibus,libri IX (On Anatomical Procedures, Part 9).[73] He introduced the nameκωνάριο (konario, often Latinised asconarium) that means cone, as in pinecone,[74] inDe usu partium corporis humani. He correctly located the gland as directly lying behind the third ventricle. He argued against the prevailing concept of it as a valve for two basic reasons: it is located outside of the brain tissue and it does not move on its own.[68]
Galen instead identified the valve as a worm-like structure in thecerebellum (later called vermiform epiphysis, known today as thevermis cerebelli orcerebellar vermis).[75] From his study on the blood vessels surrounding the pineal gland he discovered the great vein of the cerebellum, later called thevein of Galen.[74][76] He could not establish any functional role of the pineal gland and regarded it as a structural support for the cerebral veins.[77]
Seventeenth-century philosopher and scientistRené Descartes discussed the pineal gland both in his first book, theTreatise 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".[67] In theTreatise of Man, he described conceptual models of man, namely creatures created by God, which consist of two ingredients, a body and a soul.[67][78] In thePassions, he split 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 gave importance to the structure as it was the only unpaired component of the brain.[67]
The Latin namepinealis became popular in the 17th century. For example, English physicianThomas Willis described aglandula pinealis in his book,Cerebri anatome cui accessit nervorum descriptio et usus (1664). Willis criticised Descartes's concept, remarking: "we can scarce[ly] believe this to be the seat of the Soul, or its chief Faculties to arise from it; because Animals, which seem to be almost quite destitute of Imagination, Memory, and other superior Powers of the Soul, have this Glandula or Kernel large and fair enough."[77]
Walter Baldwin Spencer at the University of Oxford gave the first description of the pineal gland in lizards. In 1886, he described an eye-like structure, which he called the pineal eye or parietal eye, that was associated with theparietal foramen and the pineal stalk.[79] The presence of a pineal body was already discovered by German zoologist Franz Leydig in 1872, in European lizards. Leydig called them the "frontal organ" (Germanstirnorgan).[80][81] In 1918, Swedish zoologistNils Holmgren described the "parietal eye" in frogs and dogfish.[82] He discovered that the parietal eyes were made up of sensory cells similar to thecone cells of the retina,[77] and suggested that it was a primitive light-sensor organ (photoreceptor).[82]
The pineal gland was originally believed to be a "vestigial remnant" of a larger organ.Epiphysan – an extract derived from the pineal glands of cattle – was historically used by veterinarians for rut suppression in mares and cows. In the 1930s it was tested on humans, and resulted in a temporary reduction in their masturbation impulse.[83] In 1917, it was known that extract of cow pineals lightened frog skin. Dermatology professorAaron B. Lerner and colleagues atYale University, hoping that a hormone from the pineal gland might be useful in treating skin diseases, isolated it and named itmelatonin in 1958.[84] The substance did not prove to be helpful as intended, but its discovery helped solve several mysteries, such as why removing a rat's pineal gland accelerated its 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 ofchronobiology.[85] Of the endocrine organs, the function of the pineal gland was the last to be discovered.[86]
The notion of a "pineal eye" is central to the philosophy of the French writerGeorges Bataille, which is analyzed at length by literary scholar Denis Hollier in his studyAgainst 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.[87] This conceptual device is explicit in his surrealist texts,The Jesuve andThe Pineal Eye.[88]
The pineal gland has also featured in other religious contexts, such as in thePrincipia Discordia, which claims it can be used to contact the goddess of discordEris.[89]
In the short story "From Beyond" byH. P. Lovecraft, a scientist creates an electronic device that emits a resonance wave, which stimulates an affected person's pineal gland, thereby allowing them to perceive planes of existence outside the scope ofaccepted reality, a translucent, alien environment that overlaps our own recognized reality. It was adapted as afilm of the same name in 1986.
The 2013 horror filmBanshee Chapter is heavily influenced by this short story.
In the episode 6 fromSeason 18 ofAmerican Dad entitled "The Wondercabinet", Steve, after listening to the radio show about new age mysticism, tries to "astrally project" himself by using his pineal gland to help him understand the meaning of life.
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