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Taxonomic and Ethnical Dispersion of The Phenomenon of Pineal Concretions in The Gerontological Context
Taxonomic and Ethnical Dispersion of The Phenomenon of Pineal Concretions in The Gerontological Context
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Abstract—The pineal gland (PG), or epiphysis, is involved in the organization of biological rhythms and
adaptive reactions of the organism by the hormone melatonin. It is shown that various factors can influence
the morphology and functional activity of the gland. Calcified concretions (corpora arenacea, brain sand) are
unique biomineral structures of the PG; the causes of their formation and their possible functional signifi-
cance have been unclear until now. To date, concrements have been found in four species of birds and 21
mammalian species, as well as in humans; they are absent in fish, amphibians, and reptiles. In this review, we
have collected the available literature data on the composition, mechanisms of formation, and possible fac-
tors affecting the accumulation of concretions in the epiphysis. Although the generally accepted point of view
is that the accumulation of pineal calcium deposits is age-dependent, the available data on PG mineralization
lead to the conclusion that there is most likely a multifactorial mechanism of concrement formation. In addi-
tion, the nature and crystallinity of the inorganic tissue of the pineal concretions suggest that corpora arena-
cea, is a regulated and physiological type of petrification rather than a pathological type. The existence of
contradictory data on the connection between the formation of brain sand and the change in the functional
activity of the PG during seasonal endocrine changes and in the aging process requires the study of deposits
and in-depth investigation.
Keywords: pineal gland, calcified concretions, melatonin, aging, functional activity of the gland
DOI: 10.1134/S2079057019020206
232
TAXONOMIC AND ETHNICAL DISPERSION 233
(a) 5 Pm (b) 20 Pm
(c) (d)
x
z
100 Pm y 48 Pm
Fig. 2. Pineal calcified concretions of humans (a, b, c) [56] and the turkey (d) [82]. Images of calcifications were obtained with
light ((a) hematoxylin and eosin staining, (d) Mallory’s stain), transmission electron (b), and synchrotron X-ray (c) microscopy.
serotonin affinity [64]; this is the rate-limiting step in However, as a rule, these limited studies are based
melatonin synthesis. Along with this, calcium acts as a on the use of one or two methods of analysis, which
noncompetitive acetyl-serotonin-methyltransferase does not make it possible to obtain a complete descrip-
inhibitor [64]. In addition, pinealocytes are character- tion of the morphology and mineral and chemical
ized by a high level of Ca metabolism, which is proba- composition of the solid-phase PG formations.
bly associated with the receptor and effector functions
of the membrane [102], and the Ca and P levels in the
epiphysis increase with age [78]. It is also noteworthy STRUCTURE AND LOCALIZATION
that the PG is characterized by a high rate of phospho- OF PG CONCRETIONS
rus metabolism as compared with various structures of Acervuli in birds have a round shape with a diame-
the brain; it is three to four times higher than in the ter from 300 μm to 2 mm and are localized singly or in
pituitary and the choroid plexus [28, 104]. clusters consisting of three to five interconnected
Histologically, pineal mammalian calcifications look grains of sand (see Fig. 2d) [82]. Two types of concre-
basophilic (blue/purple color in hematoxylin and eosin tions are detected in mammals: the first consists of
staining), concentrically twisted structures (Fig. 2, 3). It single stones with a concentric, laminar structure,
was previously believed that the von Kossa method is while the second is represented by a grape-, raspberry-
suitable for the identification of brain sand, but, in fact, it , or mulberry-like structure consisting of a large num-
can only be used to detect phosphates [29, 83]. Pineal ber of interconnected nodes (nodules, Fig. 2a–2c)
stones are studied with histochemical methods (potas- [39, 56, 90, 105]. Both types often coexist together
sium pyroantimonate [51], alizarin red S [30, 82]), elec- [56]; there are also grains of irregular shape.
tronic, transmission and scanning microscopy in combi- Mammalian concretions reach a size of 2–3 μm,
nation with X-ray microanalysis (Fig. 2) [56]. forming conglomerates of up to 1 mm or more.
(a) (b)
10 Pm 10 Pm
(c) (d)
10 Pm 10 Pm
Fig. 3. Calcified concretions of the arctic fox pineal gland. (a, c, d) Hematoxylin and eosin staining; (b) Masson-Goldner staining.
Our study on arctic foxes (Vulpes lagopus, Carni- the gland, and their formation is associated with the
vora, Mammalia) showed that most of the concretions mineralization of collagen fibers [82].
found in animal PGs have a concentric structure with
alternating light and dark-colored rings (in the stan-
dard hematoxylin and eosin staining method, Fig. 3a). MECHANISMS
Whole concretions or their individual rings were OF CONCRETION FORMATION
coloured pink and/or light green with Masson–Gold-
ner staining; some of the concrements contained black To date, there is no clear understanding of how and
rings (Fig. 3b). Some grains of sand were intensively why calcium concretions form, but there are some
dark formations without distinguishable rings (Fig. 3c), assumptions concerning the possible mechanisms of
while others seemed to be hollow structures (Fig. 3d). their formation. Among them are the deterioration of
In mammals, concrements can be located both in Ca2+-dependent ATPase, structural changes in cal-
the pial capsule covering the gland and forming septae cium channels, or permanent depolarization of the
(meningeal nodules) and inside the parenchyma, calcium pump, which lead to restricted calcium excre-
mainly in the distal part of the epiphysis (Table 1) [30, tion from the cell [60], and pinealocytes death or
60, 64, 104, 105]. Differences in the concretion struc- degeneration, which entails a general decrease in PG
ture are noted depending on their localization [30]. activity [51, 90].
The brain sand located on the gland periphery is rep- Some researchers believe that concretions form at
resented by particles in the form of concentric ring for- the site of degraded pinealocytes [40, 62], while others
mations, while large conglomerates consisting of [72] associate brain sand formation with the func-
smaller particles are found in the central part [56]. The tional activity of mast cells located in the subcapsular
aggregation of the latter can occur according to the zone and around the blood vessels near the forming
type of element formation in the form of mulberry ber- crystals. Still others believe that both pinealocytes and
ries or “lamination,” when the aggregate is covered
collagen fibers are involved in this process [60, 82,
with a common plate [56]. Figure 4 shows various
ways of concretion formation. 105], while a fourth group believes that the specific
arachnoid cells play a key role in the formation of cal-
As for concretions in the epiphysis of birds, extrap- cium deposits in the pineal capsule and the protruding
ineal calcifications, i.e., those located in the choroid septae [102, 104]. The latter mechanism is similar to
plexus, are found only in geese [102]. These struc- meningeal calcification and has been found in rats
tures, like those in mammals, are characterized by a [104] and pigs [64]. The theory and patterns of brain
pronounced laminar structure. Currently, turkey is the sand formation are described in greater detail in the
only bird species in which concretions are found inside review by E.E. Zvereva [2].
Table 1. (Contd.)
The presence
Class Order Family Species/genus and localization Source
of calcifications
Carnivora Canidae Dog Canis lupus familiaris – [47]
Fox Vulpes vulpes L., 1758 – [9]
Raccoon dog Nyctereutes + In a gland capsule [9]
procyonoides Gray, 1834
Arctic fox Vulpes lagopus L., 1758 + In the parenchyma [9, 30]
of the distal part of the
organ, in the capsule
and in the septae
Procyonidae Crab-eating raccoon Procyon – [38]
cancrivorus Cuvier, 1798
Coati Nasua nasua L., 1766 + In the distal part [43]
of the body
Mustelidae Mink Mustela vison Schreber, 1777 + In the parenchyma, [102]
in the capsule of the
ventral part of the gland
Perissodactyla Equidae Horse Equus L., 1880 + [34]
– [61]
Donkey Equus asinus L., 1758 + [41]
Primates Cercopithecidae Rhesus macaque Macaca mulatta + [68]
Zimmermann, 1780
Cebidae Tufted capuchin + [21]
Sapajus apella L., 1758
Aggregated structure
Core Concentric
ring structure
Fig. 4. Possible ways of the formation of calcified concretions (according to [56]). The concentric ring structure formed from one
“core” or hotbed under conditions of a low density of the formation of such particles “accumulates” additional layers, becoming
similar to mulberry berries, whereas it aggregates into a single conglomerate when several hot spots occur.
which may be associated not only with their absence [77]. A study by Turkish scientists [99] showed that the
but also with the sensitivity of research methods, small degree of gland calcification significantly increases
sample size, and other circumstances. To date, pineal with age, especially in men, but the index decreases
nodules have been found in four species of birds and 21 with height above mean sea level and intensity of sun-
species of mammals (Table 1). In many cases, the light exposure in the region of residence.
number of nodules and/or the degree of gland calcifi-
cation positively correlates with the age of the study It is possible that skin pigmentation is also associ-
object. The generally accepted point of view is the age- ated with epiphysis functioning: calcifications are
dependent nature of the accumulation of pineal cal- found in 19.2% of Indians, 15.6% of indigenous Fiji-
cium deposits [15, 30, 40, 90]. ans living in Fiji [74], and 9.8% of dark-skinned peo-
There are also several studies showing that the ple and 16% of fair-skinned people living in the
decrease in melatonin synthesis observed with age United States [14]. However, K.-J. Fan [42] recorded
correlates with an increase in Ca2+ deposits [62, 90], a quite high level of concretion occurrence in dark-
which is most likely associated with a decrease in the skinned people in America—70%.
functioning of PG β-adrenergic receptors [50].
Despite this, some researchers still follow the point of There is convincing evidence of the regulatory role
view concerning the age-independent nature of PG of the epiphysis in the functioning of the human
calcification [72, 97]. reproductive system [79]; therefore, gender is another
factor affecting the gland calcification. In most cases,
In the Mongolian gerbil, it was shown that exoge- it is observed more often in men (Table 2). However,
nous melatonin [101], bilateral upper cervical gangli- to date, it is not known for certain how these or other
onectomy at an early age [32], and also sympathetic factors influence brain-sand formation, and the rea-
denervation of the PG [86] inhibited concretion for-
son for the differences in the occurrence of concre-
mation, while psychosocial and acute immobilization
stress [49, 75] and a short photoperiod [65] led to an tions between large and small races, as well as between
increase in the degree of gland calcification. Based on different nations and ethnic groups, remains unclear.
the results of these studies, it is logical to assume that The available data on PG calcification leads to the
the occurrence of concretions is directly related to the conclusion that there is most likely a mechanism of
PG functional activity [3, 32, 49, 65, 75, 86, 101]. Infor- concrement formation that depends on many factors
mation concerning the influence of the PG functional
activity on brain-sand formation is rare and fragmen- [102]. In addition, the nature and crystallinity of the
tary. It was revealed that an increase in the number and inorganic tissue of pineal concretions suggest that the
volume of calcium-containing secretory vacuoles in corpora arenacea is a regulated and physiological,
animal pinealocytes is observed at various endocrine rather than a pathological, type of organ petrification
shifts: the hibernation and anestrous phase in the gar- [26, 72, 96].
den dormouse (Eliomys quercinus L., 1766, Rodentia) Compared to other biomineralization examples,
[88], the proestrus phase in the mole (Talpa europaea
L., 1758, Insectivora) [80], and at the beginning of the enamels and dentin, pineal nodules are close to the
warm period or sexual rest in the hedgehog (Erinaceus latter in chemical composition and crystallographic
europaeus L., 1758, Insectivora) [81] and Mongolian properties, but they differ greatly in the amount of free
gerbil [106]. In sheep, the degree of calcification is sig- phosphorus, which is absent in nodules but is abun-
nificantly higher in individuals in the postpuberty dant in dentine [26]. Some researchers believe that PG
period than in immature and sexually mature animals calcification is similar to bone formation [96]. The
[27]. According to R.A. Zimmerman et al. [111], the existence of conflicting data on the connection of
number of concretions in humans increases signifi- between brain-sand formation with changes in the PG
cantly during puberty due to functional load on the functional activity during endocrine rearrangements
PG. It is assumed that the number of deposits may and in the aging process of the organism raises the
vary during life, i.e., calcifications are likely to have a question of pineal deposit research in a series of rele-
dynamic nature [32]. vant and necessary in-depth studies.
Studies in humans show that the degree of calcifi-
cation varies in different decades of life and varies
among nations and populations living in different time ACKNOWLEDGMENTS
zones (Table 2) [14, 25, 33, 36, 42, 74, 77]. This is
probably due to changes in the functional activity of The authors express their deep gratitude to Ph.D. E.A. Khizh-
the organ under the influence of the light regime in a kin for his help with the preparation of the illustrative mate-
particular region. The lowest frequency of pineal con- rial, to Alexandra Elbakyan, and to the reviewers of the
cretions was recorded for residents of Gambia (1.3%) journal, for careful consideration of the article and the most
[16], Nigeria (5%) [36], and Japan (9.9%) [33]. How- valuable comments and suggestions, which were taken into
ever, among Ugandans, this indicator reaches 43% account during editing.
FUNDING 12. Abbassioun, K., Aarabi, B., and Zarabi, M., A com-
parative study of physiologic intracranial calcifica-
The study was carried out under state order (project tions, Pahlavi Med. J., 1978, vol. 9, no. 2, pp. 152–166.
no. 0218-2019-0073) and co-financed by the Russian
13. Abou-Easa, K., Tousson, E., and Abd-El-Gawad, M.,
Foundation for Basic Research, grant no. 18-34-00035. Involution signs during the postnatal life in the pineal
tissue of buffalo and camel, Nat. Sci., 2009, vol. 7,
no. 9, pp. 35–44.
COMPLIANCE WITH ETHICAL STANDARDS
14. Adeloye, A. and Felson, B., Incidence of normal
The authors declare that they have no conf lict of in- pineal gland calcification in skull roentgenograms of
terest. This article does not contain any studies involving black and white Americans, Am. J. Rentgenol., 1974,
animals or human participants performed by any of the au- vol. 122, no. 3, pp. 503–507.
thors. 15. Admassie, D. and Mekonnen, A., Incidence of normal
pineal and choroids plexus calcification on Brain CT
(computerized tomography) at Tikur Anbessa Teach-
REFERENCES ing Hospital Addis Ababa, Ethiopia, Ethiop. Med. J.,
2009, vol. 47, no. 1, pp. 55–60.
1. Gul’kov, A.N., Reva, I.V., Reva, G.V., et al., Corpora
arenacea of the epiphysis with cerebral ischemia, Fun- 16. Akano, A. and Bickler, S.W., Pineal gland calcifica-
dam. Issled., 2014, vol. 4, no. 10, pp. 654–659. tion in sub-Saharan Africa, Clin. Radiol., 2003, vol. 58,
no. 4, pp. 336–337.
2. Zvereva, E.E., Theory and formation of corpora arena- 17. Aljarba, N. and Abdulrahman, A.A., Pineal gland cal-
cea in the pineal gland: a literature review, Krymsk. Zh. cification within Saudi Arabian populations, J. Anat.
Eksp. Klin. Med., 2016, vol. 6, no. 1, pp. 32–37. Soc. India, 2017, vol. 66, no. 1, pp. 43–47.
3. Ivanov, S.V., Age morphology of the human epiphysis: 18. Arendt, J., Melatonin and the pineal gland: influence
study in vivo, Usp. Gerontol., 2007, vol. 20, no. 2, on mammalian seasonal and circadian physiology,
pp. 60–65. Rev. Reprod., 1998, vol. 3, no. 1, pp. 13–22.
4. Ivanov, S.V. and Kostoglodov, Yu.K., Morphological 19. Baconnier, S. and Lang, S.B., Calcite microcrystals in
and chronoepidemiological basis for lunasensory the pineal gland of the human brain: Second harmonic
pineal gland function in the context of the redumer generators and possible piezoelectric transducers,
hypothesis of aging, Adv. Gerontol., 2011, vol. 1, no. 3, IEEE Trans. Dielectr. Electr. Insul., 2004, vol. 11, no. 2,
pp. 220–222. pp. 203–209.
5. Karmanova, L.V., Age-related morphological features 20. Barcelos, R., Filadelpho, A., Baroni, S., and Graça, W.,
of the pineal gland of the inhabitants of Syktyvkar city The morphology of the pineal gland of the Magellanic
(Komi Republic), Zdorov’e Chel. Severe, 2009, no. 2, penguin (Spheniscus magellanicus Forster, 1781), J.
pp. 24–25. Morphol., 2015, vol. 32, no. 3, pp. 149–156.
6. Kravchuk, E.I. and Kravchuk, V.I., Morfometrich- 21. Barros, R.A.C., Anatomia macroscópica e
eskaya vozrastnaya transformatsiya shishkovidnogo tela microscópica da glândula pineal do macaco Cebus
cheloveka (Morphometric Age-Related Transforma- apella, PhD Thesis, São Paulo: Univ. de São Paulo,
tion of the Human Pineal Gland), Tver, 1956. 2006.
7. Kuzemtseva, L.V., Morphology of the pineal gland in 22. Becker, U.G. and Vollrath, L., 24-Hour-variation of
pigs during ontogenesis and in post-vaccination stress, pineal gland volume, pinealocyte nuclear volume and
Cand. Sci. (Vet.) Dissertation, Izhevsk: Ural. Gos. S-kh. mitotic activity in male Sprague-Dawley rats, J. Neural
Akad., 2004. Transm., 1983, vol. 56, nos. 2–3, pp. 211–221.
8. Paskalev, D., Radoinova, D., and Galunska, B., Doc- 23. Bhatnagar, K.P. and Hoffman, R.A., Calcareous con-
tor Zakharina Dimitrova (1873–1940): a pioneer in cretions in the pineal gland of the long-tongued bat,
the study of the epiphysis microstructure, Nefrologiya, Anoura caudifer, Proc. X Int. Bat Research Conf., Bos-
2011, vol. 15, no. 2, pp. 115–118. ton, 1995.
9. Sergina, S.N., Ilyukha, V.A., Uzenbaeva, L.B., et al., 24. Bhatnagar, S. and Lall, S.B., Paradigm shifts in the
Morphofunctional activity of the pineal gland in mem- histochemical profile of enzymes in the pineal gland of
bers of the Canidae family depending on the season, Rhinopoma kinneari Wroughton (Microchiroptera:
Materialy XXIII s”ezda Fiziologicheskogo obshchestva Mammalia), Ann. Neurosci., 2010, vol. 15, no. 1,
im. I.P. Pavlova (Proc. XXIII Congr. of Pavlov Physio- pp. 11–16.
logical Society), Voronezh: Istoki, 2017, pp. 2473– 25. Bhatti, I.H. and Khan, A., Pineal calcification, J. Pak.
2475. Med. Assoc., 1977, vol. 27, no. 4, pp. 310–312.
10. Fokin, E.I., Morphology of human pineal gland in late 26. Bocchi, G. and Valdre, G., Physical, chemical, and
postnatal ontogenesis, Alzheimer’s disease, and mineralogical characterization of carbonate-hydroxy-
schizophrenia, Cand. Sci. (Med.) Dissertation, Mos- apatite concretions of the human pineal gland, J.
cow, 2008. Inorg. Biochem., 1993, vol. 49, no. 3, pp. 209–220.
11. Khelimskii, A.M., The histophysiology of colloid and 27. Bolat, D., Kürüm, A., and Canpolat, S., Morphology
corpora arenacea of the pineal gland: a histochemical and quantification of sheep pineal glands at pre-
study, Probl. Endokrinol., 1969, vol. 15, no. 5, pp. 50– pubertal, pubertal and post-pubertal periods, Anat.
54. Histol. Embryol., 2018, vol. 47, no. 4, pp. 338–345.
28. Bonewald, L.F., Harris, S.E., Rosser, J., et al., The gland in Nasua nasua–coati (L., 1766), Anat. Histol.
turnover of phosphate in the pineal body compared Embryol., 2008, vol. 37, no. 6, pp. 464–468.
with that in other parts of the brain, Biochem. J., 1947, 44. Fındιklι, E., Inci, M.F., Gökçe, M., et al., Pineal
vol. 41, no. 3, pp. 398–403. gland volume in schizophrenia and mood disorders,
29. Boskey, A., Von Kossa staining alone is not sufficient Psychiatr. Danubina, 2015, vol. 27, no. 2, pp. 150–158.
to confirm that mineralization in vitro represents bone 45. Fiske, V.M., Bryant, G.K., and Putnam, J., Effect of
formation, Calcified Tissue Int., 2003, vol. 72, no. 5, light on the weight of the pineal in the rat, Endocrinol-
pp. 537–547. ogy, 1960, vol. 66, pp. 489–491.
30. Bulc, M., Lewczuk, B., Prusik, M., et al., Calcium
concrements in the pineal gland of the Arctic fox (Vul- 46. Ghosh, S. and Haldar, C., Histology and immunohis-
pes lagopus) and their relationship to pinealocytes, glial tochemical localization of different hormone receptors
cells and type I and III collagen fibers, Pol. J. Vet. Sci., (MT1, MT2, AR, GR, ERα) in various organs (spleen,
2010, vol. 13, no. 2, pp. 269–278. thymus, ovary, uterus and testes) of Indian goat C. hir-
cus, Int. J. Res. Stud. Biosci., 2015, vol. 3, pp. 50–62.
31. Câmara, F.V., Lopes, I.R., de Oliveira, G.B., et al.,
The morphology of the pineal gland of the yellow 47. Gomes, L.A., Estudo morfológico da glâdula pineal
toothed cavy (Galea spixii Wagler, 1831) and red- no cão, PhD Thesis, São Paulo: Univ. de São Paulo,
rumped agouti (Dasyprocta leporine L., 1758), Microsc. 2003.
Res. Tech., 2015, vol. 78, no. 8, pp. 660–666. 48. Grosshans, M., Vollmert, C., Vollstaedt-Klein, S.,
32. Champney, T.H., Joshi, B.N., Vaughan, M.K., and et al., The association of pineal gland volume and body
Reiter, R.J., Superior cervical ganglionectomy results mass in obese and normal weight individuals: a pilot
in the loss of pineal concretions in the adult male gerbil study, Psychiatr. Danubina, 2006, vol. 28, no. 3,
(Meriones unguiculatus), Anat. Rec., 1985, vol. 211, pp. 220–224.
no. 4, pp. 465–468. 49. Heinzeller, T., Impact of psychosocial stress on pineal
33. Chiba, M. and Yamada, M., About the calcification of structure of male gerbils (Meriones unguiculatus,
the pineal gland in the Japanese, Psychol. Clin. Neuro- Cricetidae), J. Pineal Res., 1985, vol. 2, no. 2, pp. 145–
sci., 1948, vol. 2, no. 4, pp. 301–303. 159.
34. Cozzi, B., Cell types in the pineal gland of the horse: 50. Henden, T., Stokkan, K.A., Reiter, R.J., et al., Age-
an ultrastructural and immunocytochemical study, associated reduction in pineal beta-adrenergic recep-
Anat. Rec., 1986, vol. 216, no. 2, pp. 165–174. tor density is prevented by life-long food restriction in
35. Daghighi, M.H., Rezaei, V., Zarrintan, S., and Pour- rats, Neurosignals, 1992, vol. 1, no. 1, pp. 34–39.
fathi, H., Intracranial physiological calcifications in 51. Humbert, W. and Pévet, P., Permeability of the pineal
adults on computed tomography in Tabriz, Iran, Folia gland of the rat to lanthanum: significance of dark
Morphol., 2007, vol. 66, no. 2, pp. 115–119. pinealocytes, J. Pineal Res., 1992, vol. 12, pp. 84–88.
36. Daramola, G.F. and Olowu, A.O., Physiological and 52. Hoffman, R.A. and Reiter, R.J., Pineal gland: influ-
radiological implications of a low incidence of pineal ence on gonads of male hamsters, Science, 1965,
calcification in Nigeria, Neuroendocrinologia, 1972, vol. 148, pp. 1609–1611.
vol. 9, no. 1, pp. 41–57.
53. Jung, D. and Vollrath, L., Structural dissimilarities in
37. Del Brutto, O.H., Mera, R.M., Lama, J., et al., Pineal different regions of the pineal gland of Pirbright white
gland calcification is not associated with sleep-related guinea-pigs, J. Neural Transm., 1982, vol. 54, nos. 1–
symptoms. A population-based study in community- 2, pp. 117–128.
dwelling elders living in Atahualpa (rural coastal Ecua-
dor), Sleep Med., 2014, vol. 15, no. 11, pp. 1426–1427. 54. Karasek, M., Smith, N.K., King, T.S., et al., Inclusion
bodies in pinealocytes of the cotton rat (Sigmodon his-
38. De Oliveira Marques, L., De Carvalho, A.F., pidus), Cell Tissue Res., 1983, vol. 232, no. 2, pp. 413–
Mançanares, A.C.F., and Mançanares, C.A.F., 420.
Estudo morfológico da glândula pineal de Procyon
cancrivorus (Cuvier, 1798) (mão-pelada), Biotemas, 55. Kawamura, N., Ishibashi, T., and Miyamoto, H.,
2010, vol. 23, no. 2, pp. 163–171. Scanning electron microscopy of brain sand in the
39. Diehl, B.J.M., Time-related changes in size of nuclei bovine pineal gland, Jpn. J. Zootech. Sci., 1986, vol. 57,
of pinealocytes in rats, Cell Tissue Res., 1981, vol. 218, no. 12, pp. 1043–1045.
pp. 427–438. 56. Kim, J., Kim, H.W., Chang, S., et al., Growth patterns
40. Doyle, A.J. and Anderson, G.D., Physiologic calcifi- for acervuli in human pineal gland, Sci. Rep., 2012,
cation of the pineal gland in children on computed vol. 2, p. 984.
tomography: prevalence, observer reliability and asso- 57. Kitay, J.I. and Altschule, M.D., The Pineal Gland:
ciation with choroid plexus calcification, Acad. A Review of the Physiologic Literature, Cambridge, MA:
Radiol., 2006, vol. 13, no. 7, pp. 822–826. Harvard Univ. Press, 1954.
41. Ebada, S., Morphological and immunohistochemical 58. Kodaka, T., Mori, R., Debari, K., and Yamada, M.,
studies on the pineal gland of the donkey (Equus asi- Scanning electron microscopy and electron probe
nus), J. Vet. Anat., 2012, vol. 5, no. 1, pp. 47–74. microanalysis studies of human pineal concretions,
42. Fan, K.J., Pineal calcification among black patients, J. Microscopy, 1994, vol. 43, no. 5, pp. 307–317.
Natl. Med. Assoc., 1983, vol. 75, no. 8, pp. 765–769. 59. Kohli, N., Rastogi, H., Bhadury, S., and Tandon, V.K.,
43. Favaron, P.O., Mançanares, C.A.F., De Carvalho, A.F., Computed tomographic evaluation of pineal calcifica-
et al., Gross and microscopic anatomy of the pineal tion, Indian J. Med. Res., 1992, vol. 96, pp. 139–142.
60. Krstić, R., A combined scanning and transmission 77. Mugondi, S.G. and Poltera, A.A., Pineal gland calci-
electron microscopic study and electron probe micro- fication (PGC) in Ugandans. A radiological study of
analysis of human pineal acervuli, Cell Tissue Res., 200 isolated pineal glands, Br. J. Radiol., 1976, vol. 49,
1976, vol. 174, no. 1, pp. 129–137. no. 583, pp. 594–599.
61. Kumar, P., Timoney, J.F., and Nagpal, S., Histologi- 78. Ongkana, N., Zhao, X.Z., Tohno, S., et al., High
cal studies on the pineal gland of the horse, Haryana accumulation of calcium and phosphorus in the pineal
Vet., 2007, vol. 46, pp. 89–91. bodies with aging, Biol. Trace Elem. Res., 2007,
62. Kunz, D., Schmitz, S., Mahlberg, R., et al., A new vol. 119, no. 2, pp. 120–127.
concept for melatonin deficit: on pineal calcification 79. Oliveira, P.F., Sousa, M., Monteiro, M.P., and
and melatonin excretion, Neuropsychopharmacology, Alves, M.G., Pineal gland and regulatory function, in
1999, vol. 21, no. 6, pp. 765–772. Encyclopedia of Reproduction, Amsterdam: Elsevier,
2018.
63. Kwak, R., Takeuchi, F., Ito, S., and Kadoya, S., Intra-
cranial physiological calcification on computed 80. Pévet, P., The pineal gland of the mole (Talpa euro-
tomography (Part 1): Calcification of the pineal paea L.), Cell Tissue Res., 1977, vol. 182, no. 2,
region, No Shinkei Geka, 1988, vol. 40, no. 6, pp. 569– pp. 215–219.
574. 81. Pévet, P., Vacuolated pinealocytes in the hedgehog
64. Lewczuk, B., Przybylska, B., and Wyrzykowski, Z., (Erinaceus europaeus L.) and the mole (Talpa euro-
Distribution of calcified concretions and calcium ions paea L.), Cell Tissue Res., 1975, vol. 159, no. 3,
in the pig pineal gland, Folia Histochem. Cytobiol., pp. 303–309.
1994, vol. 32, no. 4, pp. 243–249. 82. Przybylska-Gornowicz, B., Lewczuk, B., Prusik, M.,
and Bulc, M., Pineal concretions in turkey (Meleagris
65. Lewinski, A., Vaughan, M.K., and Champney, T.H., gallapavo) as a result of collagen mediated calcifica-
Darkexposure increases the number of pineal concre- tion, Histol. Histopathol., 2009, vol. 24, pp. 407–415.
tions in male gerbils (Meriones unguiculatus), IRCS
Med. Sci., 1983, vol. 11, no. 11, pp. 977–978. 83. Puchtler, H. and Meloan, S.N., Demonstration of
phosphates in calcium deposits: a modification of von
66. Lima, E., Santana, M., Castro, M.B., et al., Micro- Kossa’s reaction, Histochemistry, 1978, vol. 56, nos. 3–
structure and morphoquantitative study of pineal 4, pp. 177–185.
gland in Santa Ines sheep, Ars Vet., 2011, vol. 27, no. 3,
pp. 186–191. 84. Ralph, C.L., The pineal gland and geographical distri-
bution of animals, Int. J. Biometeorol., 1975, vol. 19,
67. Luchetti, F., Canonico, B., Betti, M., et al., Melatonin no. 4, pp. 289–303.
signaling and cell protection function, FASEB J., 2010, 85. Rath, M.F., Coon, S.L., Amaral, F.G., et al., Mela-
vol. 24, no. 10, pp. 3603–3624. tonin synthesis: acetylserotonin O-methyltransferase
68. Lukaszyk, A. and Reiter, R.J., Histophysiological evi- (ASMT) is strongly expressed in a subpopulation of
dence for the secretion of polypeptides by the pineal pinealocytes in the male rat pineal gland, Endocrinol-
gland, Am. J. Anat., 1975, vol. 143, no. 4, pp. 451–464. ogy, 2016, vol. 157, no. 5, pp. 2028–2040.
69. Luke, J., Fluoride deposition in the aged human pineal 86. Reiter, R.J., Welsh, M.G., and Vaughan, M.K., Age-
gland, Caries Res., 2001, vol. 35, no. 2, pp. 125–128. related changes in the intact and sympathetically
70. Mahlberg, R., Kienast, T., Hädel, S., et al., Degree of denervated gerbil pineal gland, Am. J. Anat., 1976,
pineal calcification (DOC) is associated with poly- vol. 146, no. 4, pp. 427–432.
somnographic sleep measures in primary insomnia 87. Renzoni, A. and Watters, P.A., Comparative observa-
patients, Sleep Med., 2009, vol. 10, no. 4, pp. 439–445. tions on the pineal body of some Australian parrots,
71. Majidinia, M., Sadeghpour, A., Mehrzadi, S., et al., Aust. J. Zool., 1972, vol. 20, no. 1, pp. 1–15.
Melatonin: a pleiotropic molecule that modulates 88. Roux, M., Richoux, J.P., and Cordonnier, J.L., Influ-
DNA damage response and repair pathways, J. Pineal ence of the photoperiod on the ultrastructure of the
Res., 2017, vol. 63, no. 1, p. e12416. pineal gland before and during the seasonal genital
cycle in the female garden dormouse (Eliomys querci-
72. Maślińska, D., Laure-Kamionowska, M., Derę- nus L.), J. Neural Transm., 1977, vol. 41, nos. 2–3,
gowski, K., and Maśliński, S., Association of mast cells pp. 209–223.
with calcification in the human pineal gland, Folia
Neuropathol., 2010, vol. 48, no. 4, pp. 276–282. 89. Sandyk, R., Pineal and habenula calcification in
schizophrenia, Int. J. Neurosci., 1992, vol. 67, nos. 1–
73. Matsunaga, M.M., Crunfli, F., Fernandens, G.M., 4, pp. 19–30.
et al., Morphologic analysis of mice’s pineal gland, J.
Morphol. Sci., 2011, vol. 28, pp. 157–160. 90. Schmid, H.A., Decreased melatonin biosynthesis, cal-
cium flux, pineal gland calcification and aging: a
74. McKay, R.T., Pineal calcification in Indians and Fiji- hypothetical framework, Gerontology, 1993, vol. 39,
ans, Trans. R. Soc. Trop. Med. Hyg., 1973, vol. 67, no. 4, pp. 189–199.
no. 2, pp. 214–216. 91. Schmid, H.A., Requintina, P. J., Oxenkrug, G. F., and
75. Milin, J., Stress-reactive response of the gerbil pineal Sturner, W., Calcium, calcification, and melatonin
gland: concretion genesis, Gen. Comp. Endocrinol., biosynthesis in the human pineal gland: a postmortem
1998, vol. 110, no. 3, pp. 237–251. study into age-related factors, J. Pineal Res., 1994,
76. Morton, D.J. and Reiter, R.J., Involvement of calcium vol. 16, no. 4, pp. 178–183.
in pineal gland function, Proc. Soc. Exp. Biol. Med., 92. Singh, R., Ghosh, S., Joshi, A., and Haldar, C.,
1991, vol. 197, no. 4, pp. 378–383. Human pineal gland: Histomorphological study in dif-
ferent age groups and different causes of death, J. Anat. 102. Vígh, B., Szél, A., Debreceni, K., et al., Comparative
Soc. India, 2014, vol. 63, no. 2, pp. 98–102. histology of pineal calcification, Histol. Histopathol.,
93. So, N., Ismail, H.I., and Osman, D.I., Morphology of 1998, vol. 13, no. 3, pp. 851–870.
the pineal gland of the one humped camel (Camelus 103. Vígh, B., Vigh-Teichmann, I., and Aros, B., Pineal
dromedaries), J. Vet. Med. Anim. Prod., 2013, vol. 3, no. 2. corpora arenacea produced by arachnoid cells in the
bat Myotis blythi oxygnathus, Z. Mikrosk.-Anat.
94. Stammer, A., Untersuchung über die Struktur und die Forsch., 1989, vol. 103, no. 1, pp. 36–45.
Innervation der Epiphyse bei Vögeln, Acta Biol. (Sze- 104. Vígh, B., Vigh-Teichmann, I., Heinzeller, T., and Tut-
ged), 1961, vol. 7, pp. 65–75. ter, I., Meningeal calcification of the rat pineal organ,
95. Stehle, J.H., Saade, A., Rawashdeh, O., et al., A sur- Histochemistry, 1989, vol. 91, no. 2, pp. 161–168.
vey of molecular details in the human pineal gland in 105. Welsh, M.G., Pineal calcification: structural and
the light of phylogeny, structure, function and chrono- functional aspects, Pineal Res. Rev., 1985, vol. 3,
biological diseases, J. Pineal Res., 2011, vol. 51, no. 1, pp. 41–68.
pp. 17–43. 106. Welsh, M.G. and Reiter, R.J., The pineal gland of the
96. Tan, D.X., Xu, B., Zhou, X., and Reiter, R.J., Pineal gerbil, Meriones unguiculatus, Cell Tissue Res., 1978,
calcification, melatonin production, aging, associated vol. 193, no. 2, pp. 323–336.
health consequences and rejuvenation of the pineal 107. Whitehead, M.T., Oh, C., Raju, A., and Choudhri, A.F.,
gland, Molecules, 2018, vol. 23, no. 2, pp. 301–332. Physiologic pineal region, choroid plexus, and dural
97. Tapp, E. and Huxley, M., The histological appearance calcifications in the first decade of life, Am. J. Neu-
of the human pineal gland from puberty to old age, J. roradiol., 2015, vol. 36, no. 3, pp. 575–580.
Pathol., 1972, vol. 108, no. 2, pp. 137–144. 108. Wurtman, R.J., Axelrod, J., and Barchas, J.D., Age
and enzyme activity in the human pineal, J. Clin.
98. Tharnpanich, T., Johns, J., Subongkot, S., et al., Endocrinol. Metab., 1964, vol. 24, no. 3, pp. 299–301.
Association between high pineal fluoride content and
pineal calcification in a low fluoride area, Fluoride, 109. Yalcin, A., Ceylan, M., Bayraktutan, O.F., et al., Age
2016, vol. 49, no. 4, pp. 472–484. and gender related prevalence of intracranial calcifica-
tions in CT imaging; data from 12,000 healthy sub-
99. Turgut, A.T., Karakaş, H.M., Özsunar, Y., et al., Age- jects, J. Chem. Neuroanat., 2016, vol. 78, pp. 20–24.
related changes in the incidence of pineal gland calci- 110. Zhang, L., Guo, H.L., Zhang, H.Q., et al., Melatonin
fication in Turkey: a prospective multicenter CT study, prevents sleep deprivation-associated anxiety-like
Pathophysiology, 2008, vol. 15, no. 1, pp. 41–48. behavior in rats: role of oxidative stress and balance
100. Uduma, F.U., Fokam, P., and Motah, M., Incidence between GABAergic and glutamatergic transmission,
of physiological pineal gland and choroid plexus calci- Am. J. Transl. Res., 2017, vol. 9, no. 5, pp. 22–31.
fications in craniocerebral computed tomograms in 111. Zimmerman, R.A. and Bilaniuk, L.T., Age-related
Douala, Cameroon, Global J. Med. Res., 2011, vol. 11, incidence of pineal calcification detected by computed
no. 1. tomography, Radiology, 1982, vol. 142, no. 3, pp. 659–
101. Vaughan, M.K., Spanel-Borowski, K., Karasek, M., 662.
et al., Action of subcutaneous implants or injections of 112. Cutting the stone. https://cameralabs.org/8630-izv-
melatonin on reproductive and metabolic variables lechenie-kamnya-bezumiya. Accessed October 5,
and pineal concretions in male gerbils (Meriones 2018.
unguiculatus), Biomed. Res., 1983, vol. 4, no. 3,
pp. 329–336. Translated by P. Kuchina