Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency
Cobalamin deficiency affects human physiology with sequelae ranging from mild fatigue to severe neuropsychiatric abnormalities. The cellular and molecular aspects of the nervous system disorders associated with hypovitaminosis B12 remain largely unknown. Growing evidence indicates that astrogliosis...
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doaj-5c1ac2edd85c45d98d8313241d4a939d2020-11-25T03:55:19ZengMDPI AGCells2073-44092020-10-0192261226110.3390/cells9102261Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin DeficiencyZuzanna Rzepka0Jakub Rok1Justyna Kowalska2Klaudia Banach3Justyna Magdalena Hermanowicz4Artur Beberok5Beata Sieklucka6Dorota Gryko7Dorota Wrześniok8Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, PolandInstitute of Organic Chemistry, Polish Academy of Science, Kasprzaka 44/52, 01-224 Warsaw, PolandDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandCobalamin deficiency affects human physiology with sequelae ranging from mild fatigue to severe neuropsychiatric abnormalities. The cellular and molecular aspects of the nervous system disorders associated with hypovitaminosis B12 remain largely unknown. Growing evidence indicates that astrogliosis is an underlying component of a wide range of neuropathologies. Previously, we developed an in vitro model of cobalamin deficiency in normal human astrocytes (NHA) by culturing the cells with <i>c</i>-lactam of hydroxycobalamin (<i>c</i>-lactam OH-Cbl). We revealed a non-apoptotic activation of caspases (3/7, 8, 9) in cobalamin-deficient NHA, which may suggest astrogliosis. The aim of the current study was to experimentally verify this hypothesis. We indicated an increase in the cellular expression of two astrogliosis markers: glial fibrillary acidic protein and vimentin in cobalamin-deficient NHA using Western blot analysis and immunocytochemistry with confocal laser scanning microscopy. In the next step of the study, we revealed <i>c</i>-lactam OH-Cbl as a potential non-toxic vitamin B12 antagonist in an in vivo model using zebrafish embryos. We believe that the presented results will contribute to a better understanding of the cellular mechanism underlying neurologic pathology due to cobalamin deficiency and will serve as a foundation for further studies.https://www.mdpi.com/2073-4409/9/10/2261astrocytesastrogliosisneurological disorderscobalaminhypovitaminosis B12 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zuzanna Rzepka Jakub Rok Justyna Kowalska Klaudia Banach Justyna Magdalena Hermanowicz Artur Beberok Beata Sieklucka Dorota Gryko Dorota Wrześniok |
spellingShingle |
Zuzanna Rzepka Jakub Rok Justyna Kowalska Klaudia Banach Justyna Magdalena Hermanowicz Artur Beberok Beata Sieklucka Dorota Gryko Dorota Wrześniok Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency Cells astrocytes astrogliosis neurological disorders cobalamin hypovitaminosis B12 |
author_facet |
Zuzanna Rzepka Jakub Rok Justyna Kowalska Klaudia Banach Justyna Magdalena Hermanowicz Artur Beberok Beata Sieklucka Dorota Gryko Dorota Wrześniok |
author_sort |
Zuzanna Rzepka |
title |
Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency |
title_short |
Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency |
title_full |
Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency |
title_fullStr |
Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency |
title_full_unstemmed |
Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency |
title_sort |
astrogliosis in an experimental model of hypovitaminosis b12: a cellular basis of neurological disorders due to cobalamin deficiency |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-10-01 |
description |
Cobalamin deficiency affects human physiology with sequelae ranging from mild fatigue to severe neuropsychiatric abnormalities. The cellular and molecular aspects of the nervous system disorders associated with hypovitaminosis B12 remain largely unknown. Growing evidence indicates that astrogliosis is an underlying component of a wide range of neuropathologies. Previously, we developed an in vitro model of cobalamin deficiency in normal human astrocytes (NHA) by culturing the cells with <i>c</i>-lactam of hydroxycobalamin (<i>c</i>-lactam OH-Cbl). We revealed a non-apoptotic activation of caspases (3/7, 8, 9) in cobalamin-deficient NHA, which may suggest astrogliosis. The aim of the current study was to experimentally verify this hypothesis. We indicated an increase in the cellular expression of two astrogliosis markers: glial fibrillary acidic protein and vimentin in cobalamin-deficient NHA using Western blot analysis and immunocytochemistry with confocal laser scanning microscopy. In the next step of the study, we revealed <i>c</i>-lactam OH-Cbl as a potential non-toxic vitamin B12 antagonist in an in vivo model using zebrafish embryos. We believe that the presented results will contribute to a better understanding of the cellular mechanism underlying neurologic pathology due to cobalamin deficiency and will serve as a foundation for further studies. |
topic |
astrocytes astrogliosis neurological disorders cobalamin hypovitaminosis B12 |
url |
https://www.mdpi.com/2073-4409/9/10/2261 |
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