Abstract
The pineal gland plays a key role in coordinating various bodily functions. The majority of pineal cells are pinealocytes, and the second largest group are glial cells, the data on which are contradictory. The present work is undertaken to study astroglial cells of the human pineal gland using an immunohistochemical method with transmitted light microscopy and, for the first time, confocal laser microscopy. Astrocytes were labeled with antibodies to glial fibrillary acidic protein (GFAP) and vimentin. A large number of GFAP- and vimentin-immunopositive structures have been found in the human pineal gland. GFAP was localized in polygonal cells located in lobules among pinealocytes, while vimentin was localized in blood vessels and rounded cells localized mainly in trabeculae and partially in pineal lobules. Both GFAP- and vimentin-immunoreactive cells had several long branching processes that penetrated the entire pineal parenchyma, forming a dense network, and ended on the surface of the pineal gland, blood vessels, and around calcifications. GFAP-immunoreactive fibers tightly entwined all calcifications (singly and in groups), while vimentin-immunopositive processes surrounded only a part of them. The study of consecutive sections of the pineal gland showed that the coincidence of the localization of GFAP and vimentin for pineal cells is not typical. It can be supposed that, in the human pineal gland, there are two separate populations of astrocyte-like cells, GFAP- or vimentin-containing, which differ not only cytochemically, but also in morphological features and localization of cell bodies, as well as in the location of processes.
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REFERENCES
Baconnier, S., Lang, S.B., Polomska, M., Hilczer, B., Berkovic, G., and Meshulam, G., Calcite microcrystals in the pineal gland of the human brain: first physical and chemical studies, Bioelectromagnetics, 2002, vol. 23, p. 488. https://doi.org/10.1002/bem.10053
Boya, J. and Calvo, J.L., Immunohistochemical study of the pineal astrocytes in the postnatal development of the cat and dog pineal gland, J. Pineal Res., 1993, vol. 15, p. 13. https://doi.org/10.1111/j.1600-079x.1993.tb00504.x
Butt, A. and Verkhratsky, A., Neuroglia: realising their true potential, Brain Neurosci. Adv., 2018, vol. 2, p. 2398212818817495. https://doi.org/10.1177/2398212818817495
Calvo, J., Boya, J., Borregon, A., and Garcia-Mauriño, J.E., Presence of glial cells in the rat pineal gland: a light and electron microscopic immunohistochemical study, Anat. Rec., 1988, vol. 220, p. 424. https://doi.org/10.1002/ar.1092200412
Csaki, A, Koves, K, Kiss, A.L., Rohlich, P., Boldogkoi, Z., Vereczki, V., Puskar, Z., Tombacz, D., and Csabai, Z., Pinealocytes cannot transport neurotropic viruses. Pinealo-to-retinal connection in prepubertal rats originates from pineal neurons: Light and electron microscopic immunohistochemical studies, Neurosci. Lett., 2021, vol. 23, p. 135517. https://doi.org/10.1016/j.neulet.2020.135517
Dossi, E., Vasile, F., and Rouach, N., Human astrocytes in the diseased brain, Brain Res. Bull., 2018, vol. 136, p. 139. https://doi.org/10.1016/j.brainresbull.2017.02.001
Fedorova, E.A., Sufieva, D.A., Grigorev, I.P., and Korzhevskii, D.E., Mast cells of the human pineal gland, Adv. Gerontol., 2018, vol. 9, p. 62. https://doi.org/10.1134/S2079057019010053
Fernández-Blanco, Á. and Dierssen, M., Rethinking intellectual disability from neuro-to astro-pathology, Int. J. Mol. Sci., 2020, vol. 21, p. 9039. https://doi.org/10.3390/ijms21239039
Fokin, E.I., Savel’ev, S.V., Gulimova, V.I., Asadchikov, E.V., Senin, R.A., and Buzmakov, A.V., The morphogenesis and spatial organization of human pineal gland concretions in Alzheimer’s disease, schizophrenia, and alcoholism, Arkh. Patol., 2006, vol. 68, p. 20.
Gomazkov, O.A., Brain astrocytes and synaptic dissonance: neurodegenerative and mental pathology, Usp. Sovr. Biol., 2020, vol. 140, p. 130. https://doi.org/10.31857/S0042132420010019
Grigorev, I.P., Fedorova, E.A., Sufieva, D.A., and Korzhevskii, D.E., Immunohistochemical studies of cell organization in the human epiphysis, Neurosci. Behav. Physiol., 2021, vol. 51, p. 546. https://doi.org/10.1007/s11055-021-01103-4
Huang, S.-K., Nobiling, R., Schachner, M., and Taugner, R., Interstitial and parenchymal cells in the pineal gland of the golden hamster, Cell Tissue Res., 1984, vol. 235, p. 327. https://doi.org/10.1007/bf00217857
Ibanez Rodriguez, M.P., Noctor, S.C., and Munoz, E.M., Cellular basis of pineal gland development: emerging role of microglia as phenotype regulator, PLoS One, 2016, vol. 11, p. e0167063. https://doi.org/10.1371/journal.pone.0167063
Korzhevskii, D.E., Sukhorukova, E.G., Kirik, O.V., and Grigorev, I.P., Immunohistochemical demonstration of specific antigens in the human brain fixed in zinc-ethanol-formaldehyde, Eur. J. Histochem., 2015, vol. 59, p. 2530. https://doi.org/10.4081/ejh.2015.253026428887
Kovacs, G.G., Cellular reactions of the central nervous system, Handb. Clin. Neurol., 2017, vol. 145, p. 13. https://doi.org/10.1016/B978-0-12-802395-2.00003-1
Lago-Baldaia, I., Fernandes, V.M., and Ackerman, S.D., More than mortar: glia as architects of nervous system development and disease, Front. Cell Dev. Biol., 2020, vol. 8, p. 611269. https://doi.org/10.3389/fcell.2020.611269
López-Muñoz, F., Calvo, J.L., Boya, J., and Carboneil, A.L., Coexpression of vimentin and glial fibrillary acidic protein in glial cells of the adult rat pineal gland, J. Pineal Res., 1992, vol. 12, p. 145. https://doi.org/10.1111/j.1600-079x.1992.tb00041.x
Lowenthal, A., Flament-Durand, J., Karcher, D., Noppe, M., and Brion, J.P., Glial cells identified by anti-α-albumin (anti-GFA) in human pineal gland, J. Neurochem., 1982, vol. 38, p. 863. https://doi.org/10.1111/j.1471-4159.1982.tb08714.x
O’Leary, L.A., Davoli, M.A., Belliveau, C., Tanti, A., Ma, J.C., Farmer, W.T., Turecki, G., Murai, K.K., and Mechawar, N., Characterization of vimentin-immunoreactive astrocytes in the human brain, Front. Neuroanat., 2020, vol. 14, p. 31. https://doi.org/10.3389/fnana.2020.00031
Papasozomenos, S.C., Glial fibrillary acidic (GFA) protein-containing cells in the human pineal gland, J. Neuropathol. Exp. Neurol., 1983, vol. 42, p. 391. https://doi.org/10.1097/00005072-198307000-00003
Pedersen, E.B., Fox, L.M., Castro, A.J., and McNulty, J.A., Immunocytochemical and electron-microscopic characterization of macrophage/microglia cells and expression of class II major histocompatibility complex in the pineal gland of the rat, Cell Tissue Res., 1993, vol. 272, p. 257. https://doi.org/10.1007/bf00302731
Sarnat, H.B. and Yu, W., Ganglion cell maturation in peripheral neuroblastic tumours of children, Clin. Neuropathol., 2022, vol. 41, p. 101. https://doi.org/10.5414/NP301450
Sato, T., Kaneko, M., Fujieda, H., Deguchi, T., and Wake, K., Analysis of the heterogeneity within bovine pineal gland by immunohistochemistry and in situ hybridization, Cell Tissue Res., 1994, vol. 277, p. 201. https://doi.org/10.1007/bf00327768
Schachner, M., Huang, S.-K., Ziegelmüller, P., Bizzini, B., and Taugner, R., Glial cells in the pineal gland of mice and rats, Cell Tissue Res., 1984, vol. 237, p. 245. https://doi.org/10.1007/bf00217142
Scharenberg, K. and Liss, L., The histologic structure of the human pineal body. (Structure and function of the epiphysis cerebri), Prog. Brain Res., 1965, vol. 10, p. 193. https://doi.org/10.1016/s0079-6123(08)63452-4
Sofroniew, M.V. and Vinters, H.V., Astrocytes: biology and pathology, Acta Neuropathol., 2010, vol. 119, p. 7. https://doi.org/10.1007/s00401-009-0619-8
Stehle, J.H., Saade, A., Rawashdeh, O., Ackermann, K., Jilg, A., Sebesteny, T., and Maronde, E., A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases, J. Pineal Res., 2011, vol. 51, p. 17. https://doi.org/10.1111/j.1600-079X.2011.00856.x
Sukhorukova, E.G., Korzhevskii, D.E., and Alekseeva, O.S., Glial fibrillary acidic protein: The component of intermediate filaments in the vertebrate brain astrocytes, J. Evol. Biochem. Physiol., 2015, vol. 51, p. 1. https://doi.org/10.1134/S0022093015010019
Verkhratsky, A., Sofroniew, M.V., Messing, A., DeLanerolle, N.C., Rempe, D., Rodríguez, J.J., and Nedergaard, M., Neurological diseases as primary gliopathies: a reassessment of neurocentrism, ASN Neuro, 2011, vol. 4, p. e00082. https://doi.org/10.1042/AN20120010
Zang, X., Nilaver, G., Stein, B.M., Fetell, M.R., and Duffy, P.E., Immunocytochemistry of pineal astrocytes, J. Neuropathol. Exp. Neurol., 1985, vol. 44, p. 486. https://doi.org/10.1097/00005072-198509000-00004
ACKNOWLEDGMENTS
The presented images were obtained using the equipment of the “Human Microbiome” Center for the Collective Use at the Institute of Experimental Medicine.
Funding
The work was supported by funding from the Russian Science Foundation (project no. 22-25-20051, https://rscf.ru/project/22-25-20051/) and the St. Petersburg Science Foundation in accordance with an agreement dated April 14, 2022, no. 47/2022.
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D.A. Sufieva: writing the text of the article, photographing and analyzing preparations, preparing illustrations; E.A. Fedorova: performing immunohistochemical reactions, photographing preparations; V.S. Yakovlev: making sections, performing immunohistochemical reactions; D.E. Korzhevskii: editing the manuscript of the article; I.P. Grigorev: design of the experiment, analysis of preparations, writing the text of the article.
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Statement on the welfare of animals. The work was performed in compliance with ethical standards, which has been confirmed by the positive conclusions of the local ethics committee of the Institute of Experimental Medicine no. 58-9/1-684 of December 11, 2009, and no. 2/22 of April 6, 2022.
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Sufieva, D.A., Fedorova, E.A., Yakovlev, V.S. et al. GFAP- and Vimentin-Immunopositive Structures in Human Pineal Gland. Cell Tiss. Biol. 17, 406–413 (2023). https://doi.org/10.1134/S1990519X23040120
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DOI: https://doi.org/10.1134/S1990519X23040120