THE PINEAL REGION OF THE MAMMALIAN BRAIN: ITS MORPHOLOGY AND HISTOLOGY IN RELATION TO FUNCTION

Abstract

The structures which are developed from the roof‐plate of the fore‐brain are partly nervous and partly glandular. The paraphysis, which has probably a glandular function in some of the lower vertebrates, is not represented in the brain of the placental mammal.The velum transversum and dorsal sac give rise to the choroid plexuses of the lateral and third ventricles. The arrangement of the choroid plexus of the third ventricle, the relationships of the dorsal sac and the histological appearances of these structures are described.The habenular commissure, which in some animals is associated anatomically with the mammalian pineal body, is probably a commissural tract of importance, but its association with the pineal body is of developmental significance only, and no functional connection exists between them. In the ammoccete and in some reptiles the habenular commissure receives nerve‐fibres from the parapineal organ or parietal eye, but with the disappearance of the latter structure in the higher vertebrates this functional connection is lost. In those mammals in which the habenular commissure is anatomically more or less bound up with the pineal body, e.g. cat, monkey, and man, occasional nerve fibres may enter the pineal body from the commissure, but have probably no functional significance. In the rat the pineal body is anatomically widely separated from the habenular commissure, and no nervous connection persists between them.The position of the pineal body in the mammalian brain is occupied in some of the lower vertebrates by two distinct structures, one lying in front of the other in the middle line. The anterior or parapineal organ gives rise to the parietal eye, the posterior or pineal organ represents the pineal body of the higher vertebrates. The parietal eye reaches its highest degree of development in certain reptiles and has been regarded as a third or mesial eye, though some doubt exists as to how far it is functional as such. The parapineal organ is not represented in the higher vertebrates, and no trace of it occurs in the mammalian brain if one excepts the nerve‐fibres already mentioned which occasionally enter the pineal body from the habenular commissure.The mammalian pineal body cannot be regarded morphologically or histologically as a vestigial structure. It is not a remnant of the parietal eye of reptiles, but an organ which persists throughout the vertebrate series and attains a high degree of specialisation in the higher members of the series.The morphology of the mammalian pineal body and its relationships to its surroundings are described. Special attention is directed to the pineal body of the rat, which furnishes a type uncomplicated by any association with it of habenular commissure, pineal recess, or posterior commissure. The pineal body of the rat is an isolated organ which lies on the surface of the brain between the cerebral hemispheres and the cerebellum. Its only apparent functional connection with the organism is vascular, and even its nerve‐supply reaches it in the form of non‐medullated fibres accompanying the blood‐vessels.Histologically the mammalian pineal body is characterised by the occurrence in it of parenchymatous cells, neuroglia and ependyma, these being the only essential tissue elements, and all developed from the evaginated wall of the roof‐plate of the fore‐brain. Connective tissue enters the pineal body with the blood‐vessels in variable amount in different species, and as a general rule increases with age, but in many adult animals, and notably in the rat and rabbit, its amount is almost negligible. There is no evidence that the connective tissue contributes any element of functional significance to the pineal body. Medullated nerve‐fibres are present in varying quantity in some species, and are derived from the posterior commissure. In Macacus rhesus and in man the medullated fibres appear to end in whorls of fine fibres which resemble complex end‐organs or neuromata. These are not found in all animals,, and their occurrence may be accidental or the vestigial remnant of the old pineal nerve. No trace of such fibres is found in those animals in which the pineal body has migrated away from its anatomical relationship with the posterior commissure, e.g. rat and rabbit.Such function as the pineal body may have would appear to reside in the parenchymatous cell, or less probably in the neuroglia cell. The parenchymatous cell is by far the more abundant, but its histological characteristics are peculiar. It is not a nerve‐cell, but its fine branches, ending in knobbed extremities, are suggestive of a receptor function of some kind. The same type of parenchymatous cell occurs in animals which have no pineal nerve, and no evidence is available that they act as receptor organs.The morphology of the pineal body rules out of account any mechanical function in the direct regulation of the flow of the cerebrospinal fluid. It is possible that in some animals proximity to the large vein of Galen or its smaller tributaries may enable the pineal body to influence the return of blood from the tela choroidea, but even this is doubtful and does not explain the function of the parenchymatous cell.The evidence in favour of an internal secretion by the pineal body has been summed up exhaustively by Tilney and Warren, and my own observations are offered in their support. It is known that the pineal body does furnish a material which, when ingested by tadpoles, brings about a rapid contraction of their melanophores. This chemical substance is extremely diffusible, and I have found it in the choroid plexus and adjacent parts of the brain in material obtained from the slaughter‐house. Its origin, however, is confined to the pineal body, as can be proved by removal of the pineal body from the rat immediately after death. The pineal body presumably manufactures a material which has an action upon melanophores exactly the opposite of that shown by the material obtained from another nervous evagination of the third ventricle—the infundibulum of the pituitary body. The latter, it is true, receives its active principles from epithelial tissues derived from another source, but there is good reason to assert that the nervous tissue of the posterior lobe of the pituitary body does modify and eventually determine their final chemical nature. Rio Del Hortega states that while he has no theory as to the function of the parenchymatous cell, he is of the opinion that it is not secretory, and if the pineal has an endocrine function the granular neuroglia cells are probably the elements concerned. The granular neuroglia cells are comparatively inconspicuous in the pineal body of the rat, yet this organ is rich in the melanophore‐stimulating substance described by McCord and Allen. It is, indeed, difficult to conceive that a vascular isolated organ such as the pineal body of the rat can have any function other than that of an endocrine gland.There are many points of resemblance between the posterior lobe of the pituitary body and the pineal body. Both are evaginations of the wall of the foire‐brain, and both are associated at some time or other in their history with secretory structures, the pituitary with the saccus vasculosus and the pineal with the choroid plexus. Here the similarity ends; the pineal body is much more vascular than the pars nervosa and contains a special cellular element, the parenchymatous cell. Lastly, in some animals the pineal body is entirely removed from the vicinity of the third ventricle, whereas the pituitary body always maintains its developmental connections with the ventricle. There is no evidence that the pineal body of the mammalian brain ever secretes directly into the cerebrospinal fluid, although there may be channels suggestive of such function formed by complications of the pineal recess in some species. In the rat there can be no question of secretion directly into the cerebrospinal fluid.It may be objected that the presence of a substance in the mammalian pineal body which brings about a contraction of the melanophores of tadpoles is no evidence of internal secretion. It is, however, evidence that the pineal body produces a special chemical substance which can act as a hormone, and its action upon the melanophores is probably only one and may be the least important of its actions. Whether the material is formed in the parenchymatous or neuroglia cell must remain for the present a matter of conjecture, but from the histological standpoint there can be no doubt that the parenchymatous cell is the chief functional element of the pineal body. Its structural peculiarities suggest a nervous rather than a secretory function, but the development of processes and clubbed endings may be merely the expression of an inherent tendency to assume the structural appearances of a nerve‐cell which cannot make any functional connection. The absence of any demonstrable granules in the cytoplasm indicative of a secretory function cannot be regarded as of much import, and the significance of the mitochondria described by Izawa (16) and others is doubtful.There are some indications that the pineal body undergoes retrogression after sexual maturity is accomplished, though not to the extent which clinical observations upon pineal tumours would appear to warrant. Cutore's (5) measurements do not support but rather confute the belief that the human pineal body undergoes retrogression after puberty, but the increase of weight in later life may be to some extent dependent upon increase in the amount of brain sand and connective tissue. Izawa (loC. cit.), as a result of measurements in the albino rat, finds that the pineal body increases most rapidly in size from birth to maturity, and thereafter a slow increase is associated with hypertrophy of the parenchymatous cells and an increase in the amount of connective tissue. In the adult human pineal body the parenchymatous cells are present in large amounts in spite of the concretions and growth of connective tissue, and in the rat even in old age the organ has all the appearance of being active and contains the melanophore‐stimulating substance in abundance. The occurrence of brain sand is interesting, and it is suggested that its deposition is dependent upon a specific action of the pineal secretion. There is no evidence to warrant the belief that the pineal body ceases to function after puberty, though its activity may be relatively diminished after this period of life.The posterior commissure appears to have no functional connection with the pineal body in the mammal, though nerve‐fibres from it may enter the latter in some species and give rise to complicated nerve‐endings. These fibres are probably vestigial remnants of the old pineal nerve.An interesting structure, the sub‐commissural organ, is found on the ventricular surface of the posterior commissure, and is continued for a short distance along the roof of the iter. Its histological features suggest that it is a receptor organ, and Dendy has ascribed to it the function of a proprioceptor, which is actuated by changes in tension of Reissner's fibre. The organ is highly developed in the mammals examined with the exception of man, in which it is rudimentary.I am indebted to Mr Richard Muir for the care with which he has prepared the photographic illustrations.The work of which the paper is a record was undertaken for the Medical Research Council.