Clinical Neuropathology, Vol. 31 – No. 6/2012 (437-439)
The discovery of oligodendroglia cells by Río-Hortega: his original articles José R. Iglesias-Rozas1 and Manuel Garrosa2 1Neuropathologist ©2012 Dustri-Verlag Dr. K. Feistle ISSN 0722-5091 DOI 10.5414/NP301001 e-pub: October 16, 2012
Key words oligodendroglia – Río-Hortega – neuroglia history – original articles
and Pathologist. Member of the University der Eberhard-KarlsUniversität Tübingen, Germany, and 2Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, INCYL, University of Valladolid, Spain
Abstract. Comment on: del Río-Hortega P. Glia with very few processes (oligodendroglia). Clin Neuropathol. 2012; 31: 440-459, originally published in Archivos de Neurobiología. 1921; 2: 16-43 and del Río-Hortega P. Are the glia with very few processes homologous with Schwann cells? Clin Neuropathol. 2012; 31: 460-462, originally published in Bol de la Soc Esp de Biol. 1922; X: 25-28.
Introduction
Correspondence to Dr. med. Dr. med. habil. José R. Iglesias-Rozas Mörikestraße 13, 71679 Asperg, Germany [email protected]
Pío del Río-Hortega (1882 – 1945) (Figure 1) has been internationally recognized for his contribution to the elucidation of the different types of glia and tumors in the central nervous system in the early moments of their characterizations. This scholar, mentor of other great scientists such as W. Penfield, was twice nominated for the Nobel Prize but was not finally awarded due to extrascientifical reasons, such as the political situation in Spain at that time. His invention of a new staining method in 1918 [1]: “The ammoniacal silver carbonate” enabled him to characterize the apolar cells or “the third element” of the nervous tissue following Cajal’s denomination because these cells did not show processes and were not neurons (first element) or astroglia (second element). By that time there were two differentiated opinions about these apolar cells: those who supported the idea that these cells lacked processes and could be undifferentiated elements (Cajal, Nissl, Robertson, Rosental, etc.) and those who thought that these cells had processes but they could not be stained because they were too fine or because of still inappropriate techniques (Hold, Alzheimer, Lugaro, etc.). Río-Hortega resolved the question by demonstrating
Figure 1. Pío del Río Hortega.
that these wrongly called apolar cells actually had processes and comprised two different types of cells: microglia and oligodendroglia. During 1919, he published a series of articles about the third element in which he made the description of microglia in the normal [2] and pathological [3] state as well as of its origin [4]. In homage to microglia discovery and characterization, these cells are known as Río-Hortega’s or Hortega’s cells. However, a fact which has not been sufficiently recognized internationally is his discovery of oligodendroglia. In his first publication on the third element, together with microglia Río-Hortega described the existence of another cell type showing very fine processes which he first named interfascicular glia for being preferentially observed aligned along the white matter fascicles [2]. Two years after this work
Iglesias-Rozas and Garrosa
he properly described and characterized this other type of neuroglia, which could not be considered protoplasmic or fibrous, and renamed it “glia with very few processes” or “oligodendroglia” since these cells showed scant number of ramifications (oligo = few; dendro = tree) [5]. In this article of 1921 RíoHortega also advanced the relation of oligodendroglia with myelination and described its development. A second article followed in 1922 [6] supporting the possibility that these cells could be homologous with Schwann cells in the central nervous system and a third contribution appeared in 1928, in which he described and reviewed thoroughly the morphological, functional, ontogenetical and pathological aspects of oligodendroglia [7]. Apart from the fact that these articles were written in Spanish, a reason which may account for the lack of international recognition of the discovery of oligodendroglia by Río-Hortega is the terminological confusion concerning the description of the components of the third element by different authors, such as the bare nuclei of Schaper, the preamoeboid cells of Rosental, the mesoglia cells of Robertson or the adendritic cells of Cajal [7]. Robertson had described in 1900 [8], with his platinum method, interstitial cells which named mesoglia cells as he supposed they were of mesodermal origin. These cells differed from the rest of neuroglia in that their processes were small and not connected with vessels or nerve cells or fibers and they seemed to have phagocytic function in pathological states. However, Robertson’s morphological and functional descriptions do not allow discerning if these mesoglia cells correspond to microglia or to small oligodendroglia elements. Cajal could neither discern oligodendroglia properly in his descriptions of the small adendritic cells because the use of his gold sublimate and formol-uranium methods did not enable him to see oligodendroglia fine expansions and therefore failed to consider these cells a different kind of neuroglia, albeit Cajal had the insight that they could be the homologous with Schwann cells in the nerve centers. Despite Río-Hortega worked in Germany (Koch Institute, Berlin) and in the United Kingdom in Oxford, by which
438 university was even made Doctor Honoris Causa, none of these original articles in Spanish have been translated into English or German. Only the article of 1922 [6] was translated into French in 1924 [9]. Because of all the above mentioned, we are happy to present the English translation of Río-Hortega’s seminal works on oligodendroglia. We have aimed at making available in present scientific English language the process of its discovery and description as well as making it widely known. Furthermore, it seems scientifically inappropriate to create new classifications, or new types and subtypes of oligodendroglia, of progenitors, etc., without having read or cited R ío-Hortega’s original articles. We acknowledge that this is partly due to the absence of having the articles available in English or German translations. Finally, the authors are also motivated by personal reasons which go back to their academic education when both were students of Prof. Luis Zamorano, who had learned the histological techniques directly from RíoHortega at “La Residencia de Estudiantes” in Madrid. Besides, Dr. Iglesias-Rozas improved his knowledge of the silver impregnation methods when working in the Institute of Neuropathology of the Free University of Berlin with Prof. Moisés Polak, also disciple of Río-Hortega. In our English version we have generally preserved Río-Hortega’s terminology except where equivalent English words of the period have gone completely out of fashion. Some of Río-Hortega’s terms are the same as those used by the Nobel Prize winner Ramón y Cajal, one of his mentors; in these cases we have chosen to retain the terms. All the illustrations appearing in the translations are taken from the original publications. Apart from corrections of dates and obvious typographical errors, we have allowed the textual citations stand in the form in which they originally appeared. We hereby present to the scientific community the first English version of the two seminal articles on oligodendroglia in which Río-Hortega published his findings in 1921 and 1922, with the hope that the modern scientist will integrate these findings with the new and efficient molecular biology and immunohistological techniques they possess
The discovery of oligodendroglia cells by Rio-Hortega: his original articles
and also paying a posthumous homage to this great Spanish histologist and neuropathologist.
Acknowledgments The authors want to thank most sincerely the Río-Hortega family and especially Dr. Juan del Río-Hortega Bereciartu in whose ownership the papers of Pío del Río-Hortega are held; they have facilitated us, with great friendliness and generosity, the use of those papers and provided us with some pictures of his own illustrations. The authors also gratefully acknowledge the assistance of Prof. Manuel J. Gayoso, director of Río-Hortega museum in the University of Valladolid for providing the original articles and for his wise comments and criticisms. We are indebted to our colleagues Roy O. Weller and Teresa Iglesias-Rozas for their time and patience in reading complete drafts of these papers and for the very valuable suggestions they have made for their improvement. We also wish to thank The Cajal Institute in Madrid and its librarian Mrs. Mª Ángeles Langa for the use of their facilities and their help in obtaining the illustrations from the original articles.
References [1]
[2] [3]
[4] [5]
[6] [7]
del Río-Hortega P. Noticia de un nuevo y fácil método para la coloración de la neuroglia y del tejido conjuntivo. Trab. Lab. Inv. Biol. 1918; 15: 367-378. del Río-Hortega P. El tercer elemento de los centros nerviosos I. La microglía en estado normal. Bol. Soc. Esp. Biol. 1919a; 9: 68-89. del Río-Hortega P. El tercer elemento de los centros nerviosos II. Intervención de la microglía en los procesos patológicos. Bol. Soc. Esp. Biol. 1919b; 9: 91-103. del Río-Hortega P. El tercer elemento de los centros nerviosos III. Naturaleza probable de la microglía. Bol. Soc. Esp. Biol. 1919c; 9: 108-120. del Río-Hortega P. Estudios sobre la neuroglía.- La glía de escasas radiaciones (oligodendroglía). Bol. R. Soc. Esp. Hist. Nat. 21: 63-92; also published in: Arch. Neurobiologia. 1921; 2: 16-43. del Río-Hortega P. ¿Son homologables la glía de escasas radiaciones y la célula de Schwann? Bol. Soc. Esp. Biol. 1922; 10: 25-28. del Río-Hortega P. Tercera aportación al conocimiento morfológico e interpretación funcional de la oligodendroglía. Mem. R. Soc. Esp. Hist. Nat. 1928; 14: 5-122.
[8] [9]
439
Robertson W. A microscopic demonstration of the normal and pathological histology of mesoglia cells. J Ment Sci. 1900; 96: 724. del Río-Hortega P. ¿La glia a radiations peu nombreuses et la cellule de Schwann sont-elles homologables? Comp. Rend. Her. Domad. Soc. Biol. 1924; 2: 818-820.
The discovery of oligodendroglia cells by Río-Hortega: his original articles José R. Iglesias-Rozas1 and Manuel Garrosa2 1Neuropathologist ©2012 Dustri-Verlag Dr. K. Feistle ISSN 0722-5091 DOI 10.5414/NP301001 e-pub: October 16, 2012
Key words oligodendroglia – Río-Hortega – neuroglia history – original articles
and Pathologist. Member of the University der Eberhard-KarlsUniversität Tübingen, Germany, and 2Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, INCYL, University of Valladolid, Spain
Abstract. Comment on: del Río-Hortega P. Glia with very few processes (oligodendroglia). Clin Neuropathol. 2012; 31: 440-459, originally published in Archivos de Neurobiología. 1921; 2: 16-43 and del Río-Hortega P. Are the glia with very few processes homologous with Schwann cells? Clin Neuropathol. 2012; 31: 460-462, originally published in Bol de la Soc Esp de Biol. 1922; X: 25-28.
Introduction
Correspondence to Dr. med. Dr. med. habil. José R. Iglesias-Rozas Mörikestraße 13, 71679 Asperg, Germany [email protected]
Pío del Río-Hortega (1882 – 1945) (Figure 1) has been internationally recognized for his contribution to the elucidation of the different types of glia and tumors in the central nervous system in the early moments of their characterizations. This scholar, mentor of other great scientists such as W. Penfield, was twice nominated for the Nobel Prize but was not finally awarded due to extrascientifical reasons, such as the political situation in Spain at that time. His invention of a new staining method in 1918 [1]: “The ammoniacal silver carbonate” enabled him to characterize the apolar cells or “the third element” of the nervous tissue following Cajal’s denomination because these cells did not show processes and were not neurons (first element) or astroglia (second element). By that time there were two differentiated opinions about these apolar cells: those who supported the idea that these cells lacked processes and could be undifferentiated elements (Cajal, Nissl, Robertson, Rosental, etc.) and those who thought that these cells had processes but they could not be stained because they were too fine or because of still inappropriate techniques (Hold, Alzheimer, Lugaro, etc.). Río-Hortega resolved the question by demonstrating
Figure 1. Pío del Río Hortega.
that these wrongly called apolar cells actually had processes and comprised two different types of cells: microglia and oligodendroglia. During 1919, he published a series of articles about the third element in which he made the description of microglia in the normal [2] and pathological [3] state as well as of its origin [4]. In homage to microglia discovery and characterization, these cells are known as Río-Hortega’s or Hortega’s cells. However, a fact which has not been sufficiently recognized internationally is his discovery of oligodendroglia. In his first publication on the third element, together with microglia Río-Hortega described the existence of another cell type showing very fine processes which he first named interfascicular glia for being preferentially observed aligned along the white matter fascicles [2]. Two years after this work
Iglesias-Rozas and Garrosa
he properly described and characterized this other type of neuroglia, which could not be considered protoplasmic or fibrous, and renamed it “glia with very few processes” or “oligodendroglia” since these cells showed scant number of ramifications (oligo = few; dendro = tree) [5]. In this article of 1921 RíoHortega also advanced the relation of oligodendroglia with myelination and described its development. A second article followed in 1922 [6] supporting the possibility that these cells could be homologous with Schwann cells in the central nervous system and a third contribution appeared in 1928, in which he described and reviewed thoroughly the morphological, functional, ontogenetical and pathological aspects of oligodendroglia [7]. Apart from the fact that these articles were written in Spanish, a reason which may account for the lack of international recognition of the discovery of oligodendroglia by Río-Hortega is the terminological confusion concerning the description of the components of the third element by different authors, such as the bare nuclei of Schaper, the preamoeboid cells of Rosental, the mesoglia cells of Robertson or the adendritic cells of Cajal [7]. Robertson had described in 1900 [8], with his platinum method, interstitial cells which named mesoglia cells as he supposed they were of mesodermal origin. These cells differed from the rest of neuroglia in that their processes were small and not connected with vessels or nerve cells or fibers and they seemed to have phagocytic function in pathological states. However, Robertson’s morphological and functional descriptions do not allow discerning if these mesoglia cells correspond to microglia or to small oligodendroglia elements. Cajal could neither discern oligodendroglia properly in his descriptions of the small adendritic cells because the use of his gold sublimate and formol-uranium methods did not enable him to see oligodendroglia fine expansions and therefore failed to consider these cells a different kind of neuroglia, albeit Cajal had the insight that they could be the homologous with Schwann cells in the nerve centers. Despite Río-Hortega worked in Germany (Koch Institute, Berlin) and in the United Kingdom in Oxford, by which
438 university was even made Doctor Honoris Causa, none of these original articles in Spanish have been translated into English or German. Only the article of 1922 [6] was translated into French in 1924 [9]. Because of all the above mentioned, we are happy to present the English translation of Río-Hortega’s seminal works on oligodendroglia. We have aimed at making available in present scientific English language the process of its discovery and description as well as making it widely known. Furthermore, it seems scientifically inappropriate to create new classifications, or new types and subtypes of oligodendroglia, of progenitors, etc., without having read or cited R ío-Hortega’s original articles. We acknowledge that this is partly due to the absence of having the articles available in English or German translations. Finally, the authors are also motivated by personal reasons which go back to their academic education when both were students of Prof. Luis Zamorano, who had learned the histological techniques directly from RíoHortega at “La Residencia de Estudiantes” in Madrid. Besides, Dr. Iglesias-Rozas improved his knowledge of the silver impregnation methods when working in the Institute of Neuropathology of the Free University of Berlin with Prof. Moisés Polak, also disciple of Río-Hortega. In our English version we have generally preserved Río-Hortega’s terminology except where equivalent English words of the period have gone completely out of fashion. Some of Río-Hortega’s terms are the same as those used by the Nobel Prize winner Ramón y Cajal, one of his mentors; in these cases we have chosen to retain the terms. All the illustrations appearing in the translations are taken from the original publications. Apart from corrections of dates and obvious typographical errors, we have allowed the textual citations stand in the form in which they originally appeared. We hereby present to the scientific community the first English version of the two seminal articles on oligodendroglia in which Río-Hortega published his findings in 1921 and 1922, with the hope that the modern scientist will integrate these findings with the new and efficient molecular biology and immunohistological techniques they possess
The discovery of oligodendroglia cells by Rio-Hortega: his original articles
and also paying a posthumous homage to this great Spanish histologist and neuropathologist.
Acknowledgments The authors want to thank most sincerely the Río-Hortega family and especially Dr. Juan del Río-Hortega Bereciartu in whose ownership the papers of Pío del Río-Hortega are held; they have facilitated us, with great friendliness and generosity, the use of those papers and provided us with some pictures of his own illustrations. The authors also gratefully acknowledge the assistance of Prof. Manuel J. Gayoso, director of Río-Hortega museum in the University of Valladolid for providing the original articles and for his wise comments and criticisms. We are indebted to our colleagues Roy O. Weller and Teresa Iglesias-Rozas for their time and patience in reading complete drafts of these papers and for the very valuable suggestions they have made for their improvement. We also wish to thank The Cajal Institute in Madrid and its librarian Mrs. Mª Ángeles Langa for the use of their facilities and their help in obtaining the illustrations from the original articles.
References [1]
[2] [3]
[4] [5]
[6] [7]
del Río-Hortega P. Noticia de un nuevo y fácil método para la coloración de la neuroglia y del tejido conjuntivo. Trab. Lab. Inv. Biol. 1918; 15: 367-378. del Río-Hortega P. El tercer elemento de los centros nerviosos I. La microglía en estado normal. Bol. Soc. Esp. Biol. 1919a; 9: 68-89. del Río-Hortega P. El tercer elemento de los centros nerviosos II. Intervención de la microglía en los procesos patológicos. Bol. Soc. Esp. Biol. 1919b; 9: 91-103. del Río-Hortega P. El tercer elemento de los centros nerviosos III. Naturaleza probable de la microglía. Bol. Soc. Esp. Biol. 1919c; 9: 108-120. del Río-Hortega P. Estudios sobre la neuroglía.- La glía de escasas radiaciones (oligodendroglía). Bol. R. Soc. Esp. Hist. Nat. 21: 63-92; also published in: Arch. Neurobiologia. 1921; 2: 16-43. del Río-Hortega P. ¿Son homologables la glía de escasas radiaciones y la célula de Schwann? Bol. Soc. Esp. Biol. 1922; 10: 25-28. del Río-Hortega P. Tercera aportación al conocimiento morfológico e interpretación funcional de la oligodendroglía. Mem. R. Soc. Esp. Hist. Nat. 1928; 14: 5-122.
[8] [9]
439
Robertson W. A microscopic demonstration of the normal and pathological histology of mesoglia cells. J Ment Sci. 1900; 96: 724. del Río-Hortega P. ¿La glia a radiations peu nombreuses et la cellule de Schwann sont-elles homologables? Comp. Rend. Her. Domad. Soc. Biol. 1924; 2: 818-820.
