Abstract
Choroid plexus, pineal gland, and habenula tend to accumulate physiologic calcifications (concrements) over a lifetime. However, until now the composition and causes of the intracranial calcifications remain unclear. The detailed analysis of concrements has been done by us using X-ray diffraction analysis (XRD), X-ray diffraction topography (XRDT), micro-CT, X-ray phase-contrast tomography (XPCT), as well as histology and immunohistochemistry (IHC). By combining physical (XRD) and biochemical (IHC) methods, we identified inorganic (hydroxyapatite) and organic (vimentin) components of the concrements. Via XPCT, XRDT, histological, and IHC methods, we assessed the structure of concrements within their appropriate tissue environment in both two and three dimensions. The study found that hydroxyapatite was a major component of all calcified depositions. It should be noted, however, that the concrements displayed distinctive characteristics corresponding to each specific structure of the brain. As a result, our study provides a basis for assessing the pathological and physiological changes that occur in brain structure containing calcifications.
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The data that support the findings (histological, IHC, XRD, XRDT, XPCT) of this study are available on request from the corresponding author.
References
Bersani G, Garavini A, Taddei I, Tanfani G, Pancheria P (1999) Choroid plexus calcification as a possible clue of serotonin implication in schizophrenia. Neurosci Lett 259:169–172. https://doi.org/10.1016/S0304-3940(98)00935-5
Bruno F, Arrigoni F, Maggialetti N, Natella R, Reginelli A, Di Cesare E, Brunese L, Giovagnoni A, Masciocchi C, Splendiani A, Barile A (2019) Neuroimaging in emergency: a review of possible role of pineal gland disease. Gland Surg 8. https://doi.org/10.21037/gs.2019.01.02
Bukreeva I, Junemann O, Cedola A, Brun F, Longo E, Tromba G, Wilde F, Chukalina MV, Krivonosov YS, Dyachkova IG, Buzmakov AV, Zolotov DA, Palermo F, Gigli G, Otlyga DA, Saveliev SV, Fratini M, Asadchikov VE (2022) Micro-morphology of pineal gland calcification in age-related neurodegenerative diseases. Med Phys. https://doi.org/10.1002/mp.16080
Buzmakov AV, Asadchikov VE, Zolotov DA, Roshchin BS, Dymshits YuM, Shishkov VA, Chukalina MV, Ingacheva AS, Ichalova DE, Krivonosov YuS, Dyachkova IG, Balzer M, Castele M, Chilingaryan S, Kopmann, (2018) A Laboratory microtomographs: design and data processing algorithms. Crystallogr Reports 63:1057–1061. https://doi.org/10.1134/S106377451806007X
Chukalina MV, Ingacheva AS, Buzmakov AV, Krivonosov YS, Asadchikov VE, Nikolaev DP (2019) A hardware and software system for tomographic research: reconstruction via regularization. Bull Russ Acad Sci Phys 83:150–154. https://doi.org/10.3103/S1062873819020084
Hu H, Cui Y, Yang Y (2020) Circuits and functions of the lateral habenula in health and in disease. Nat Rev Neurosci 21:277–295. https://doi.org/10.1038/s41583-020-0292-4
Hughes JM, Cameron M, Crowley KD (1989) Structural variations in natural F, OH, and Cl apatites. Am Miner 74:870–876
Khokhriakov I, Beckmann F, Lottermoser L (2017) Integrated control system environment for high-throughput tomography, Proc. SPIE 10391, Developments in X-Ray Tomography XI, 103911H1–10. https://doi.org/10.1117/12.2275863
Kim J, Kim HW, Chang S, Kim JW, Je JH, Rhyu IJ (2012) Growth patterns for acervuli in human pineal gland. Sci Rep 2:984. https://doi.org/10.1038/srep00984
Kodaka T, Mori R, Debari K, Yamada M (1994) Scanning electron microscopy and electron probe microanalysis studies of human pineal concretions. J Electron Microsc 43:307–317. https://doi.org/10.1093/oxfordjournals.jmicro.a051117
Korzhevskii DE (1997) The formation of psammoma bodies in the choroid plexus of the human brain. Morfologiia 111:46–49. PMID: 9244548
Kunz D, Schmitz S, Mahlberg R, Mohr A, Stöter C, Wolf K-J, Herrmann WM (1999) A new concept for melatonin deficit: on pineal calcification and melatonin excretion. Neuropsychopharmacology 21:765–772. https://doi.org/10.1016/S0893-133X(99)00069-X
Lewczuk B, Przybylska B, Wyrzykowski Z (1994) Distribution of calcified concretions and calcium ions in the pig pineal gland. Folia Histochem Cytobiol 32:243–249. PMID: 7758619
Mabie CP, Wallace BM (1974) Optical, physical and chemical properties of pineal gland calcifications. Calc Tis Res 16:59–71. https://doi.org/10.1007/BF02008213
Macpherson P, Matheson MS (1979) Comparison of calcification of pineal, habenular commissure and choroid plexus on plain films and computed tomography. Neuroradiology 18:67–72. https://doi.org/10.1007/BF00344824
Maheshwari U, Huang SF, Sridhar S, Keller A (2022) The interplay between brain vascular calcification and microglia. Front Aging Neurosci 14:1–14. https://doi.org/10.3389/fnagi.2022.848495
Michotte Y, Lowenthal A, Knaepen L, Collard M, Massart DL (1977a) A morphological and chemical study of calcification of the pineal gland. J Neurol 215:209–219. https://doi.org/10.1007/BF00312479
Michotte Y, Massart DL, Lowenthal A, Knaepen L, Pelsmaekers J, Collard M (1977b) Morphological and chemical study of calcification of the choroid plexus. J Neurol 216:127–133. https://doi.org/10.1007/BF00312946
Modic MT, Weinstein MA, Rother AD, Erenberg G, Duchesneau PM, Kaufman B (1980) Calcification of the choroid plexus visualized by computed tomography. Radiology 135:369–372. https://doi.org/10.1148/radiology.135.2.7367628
Møller M, Gjerris F, Hansen HJ, Johnson E (1979) Calcification in a pineal tumour studied by transmission electron microscopy, electron diffraction and x-ray microanalysis. Acta Neurol Scand 59(4):178–187. https://doi.org/10.1111/j.1600-0404.1979.tb02928.x
Moosmann J, Ershov A, Weinhardt V, Baumbach T, Prasad MS, LaBonne C, Xiao X, Kashef HR (2014) Time-lapse X-ray phase-contrast microtomography for in vivo imaging and analysis of morphogenesis. Nat Protoc 9:294–304. https://doi.org/10.1038/nprot.2014.033
Novier A, Nicolas D, Krstic R (1996) Calretinin immunoreactivity in pineal gland of different mammals including man. J Pineal Res 21:121–130. https://doi.org/10.1111/j.1600-079x.1996.tb00279.x
Raven C (1998) Numerical removal of ring artifacts in microtomography. Am Inst Phys 69:2978–2980. https://doi.org/10.1063/1.1149043
Rigaku Oxford Diffraction (2019) CrysAlisPro Software System. Version. 1.171.39.46 (Wroclaw, Poland)
Sandyk R (1992) Pineal and habenula calcification in Schizophrenia. Int J Neurosci 67:19–30. https://doi.org/10.3109/00207459208994773
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez J-Y, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682. https://doi.org/10.1038/nmeth.2019
Serot J-M, Bene M-C, Faure GC (2003) Choroid plexus, ageing of the brain, and Alzheimer’s disease. Front Biosci 8:515–521. https://doi.org/10.2741/1085
Shuangshoti S, Netsky M (1970) Human choroid plexus: morphologic and histochemical alteration with age. Am J Anat 128:73–96. https://doi.org/10.1002/aja.1001280107
Song J (2019) Pineal gland dysfunction in Alzheimer’s disease: relationship with the immune-pineal axis, sleep disturbance, and neurogenesis. Mol Neurodegener. https://doi.org/10.1186/s13024-019-0330-8
Snigirev A, Snigireva I, Kohn V, Kuznetsov S, Schelokov I (1995) On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation. Rev Sci Instrum 66:5486–5492. https://doi.org/10.1063/1.1146073
Tan D, Xu B, Zhou X, Reiter RJ (2018) Pineal calcification, melatonin production, aging, associated health consequences and rejuvenation of the pineal gland. Molecules 23:301. https://doi.org/10.3390/molecules23020301
Vigh B, Szél A, Debreceni K, Fejér Z, Manzano e Silva MJ, Vigh Teichmann I (1998) Comparative histology of pineal calcification. Histol Histopathol 13:851–870
Vo NT, Atwood RC, Drakopoulos M, Connolley T (2021) Data processing methods and data acquisition for samples larger than the field of view in parallel-beam tomography. Opt Express 29:17849–17874. https://doi.org/10.1364/OE.418448
Wilde F, Ogurreck M, Greving I, Hammel JU, Beckmann F, Hipp A, Lottermoser L, Khokhriakov I, Lytaev P, Dose T, Burmester H, Müller M, Schreyer A (2016) Micro-CT at the imaging beamline P05 at PETRA III. AIP Conf Proc. https://doi.org/10.1063/1.4952858
Wolburg H, Paulus W (2010) Choroid plexus: biology and pathology. Acta Neuropathol 119:75–88. https://doi.org/10.1007/s00401-009-0627-8
Acknowledgements
X-ray diffraction experiments were performed within the State assignment of FSRC "Crystallography and Photonics" of Russian Academy of Sciences using the equipment of the Shared Research Center FSRC “Crystallography and Photonics” RAS. This work was performed within the State Assignment of FSRC "Crystallography and Photonics" RAS in part of X-ray studies.
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O.J. and S.V.S. conceived and designed the research; O.J. and D.A.O. performed the research and acquired the histological and IHC data; A.G.I. performed the research and acquired the XRD data; I.B., M.F., A.C., and F.W. performed the research and acquired the XPCT data; D.A.Z., I.G.D., and Yu.S.K. performed the research and acquired the XRDT data; O.J., S.V.S., I.B., A.G.I., and D.A.Z. analyzed and interpreted the data. All authors were involved in drafting and revising the manuscript.
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The study was carried out on autopsy material obtained from the collection of Federal State Scientific Institution Research Institute of Human Morphology (Moscow, Russian Federation). All protocols were approved by the Ethical Committee of the Research Institute of Human Morphology of the Russian Academy of Medical Sciences (now FSSI Research Institute of Human Morphology) (No. 6A of October 19, 2009) and are in correspondence with instructions of the Declaration of Helsinki including points 7–10 for human material from 12.01.1996 with the last amendments from 19.12.2016.
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Junemann, O., Ivanova, A.G., Bukreeva, I. et al. Comparative study of calcification in human choroid plexus, pineal gland, and habenula. Cell Tissue Res 393, 537–545 (2023). https://doi.org/10.1007/s00441-023-03800-7
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DOI: https://doi.org/10.1007/s00441-023-03800-7