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Astrocyte ablation induced by La-aminoadipate (L-AAA) potentiates remyelination in a cuprizone demyelinating mouse model

  • Soheila Madadi
  • Parichehr Pasbakhsh
  • Fatemeh Tahmasebi
  • Keywan Mortezaee
  • Maryam Khanehzad
  • Fatemeh Beigi Boroujeni
  • Golaleh Noorzehi
  • Iraj Ragerdi KashaniEmail author
Original Article

Abstract

Chronic demyelination in the central nervous system (CNS) is accompanied by an increase in the number of reactive astrocytes and astrogliosis. There are controversial issues regarding astrocytes and their roles in demyelinating diseases in particular for multiple sclerosis (MS). We aimed to evaluate possible roles for pharmacologic astrocyte ablation strategy using La-aminoadipate (L-AAA) on remyelination in a cuprizone model of demyelination. Male C57BL/6 mice were fed with 0.2% cuprizone for 12 weeks followed by 2-week administration of L-AAA through a cannula inserted 1 mm above the corpus callosum. Rotarod test showed a significant decrease in the range of motor coordination deficits after ablation of astrocytes in mice receiving cuprizone. Results of Luxol fast blue (LFB) and transmission electron microscopy (TEM) for evaluation of myelin content within the corpus callosum revealed a noticeable rise in the percentage of myelinated areas and in the number of myelinated fibers after L-AAA administration in the animals. Astrocyte ablation reduced protein expressions for GFAP (an astrocyte marker) and Iba-1 (a microglial marker), but increased expression of Olig2 (an oligodendrocyte marker) assessed by immunofluorescence. Finally, expression of genes related to recruitment of microglia (astrocyte chemokines CXCL10 and CXCL12) and suppression of oligodendrocyte progenitor cell (OPC) differentiation (astrocyte peptides ET-1 and EDNRB) showed a considerable decrease after administration of L-AAA (for all p < 0.05). These results are indicative of improved remyelination after ablation of astrocytes possibly through hampering microgliosis and astrogliosis and a further rise in the number of matured Olig2+ cells.

Keywords

Astrocyte ablation Cuprizone La-aminoadipate (L-AAA) Multiple sclerosis (MS) Remylination Corpus callosum 

Notes

Acknowledgments

The present study has been supported by Tehran University of Medical Sciences and Health Services, Tehran, Iran (Grant number 95-04-30-33652).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Soheila Madadi
    • 1
  • Parichehr Pasbakhsh
    • 1
  • Fatemeh Tahmasebi
    • 1
  • Keywan Mortezaee
    • 2
  • Maryam Khanehzad
    • 1
  • Fatemeh Beigi Boroujeni
    • 1
  • Golaleh Noorzehi
    • 3
  • Iraj Ragerdi Kashani
    • 1
    Email author
  1. 1.Department of Anatomy, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Anatomy, School of MedicineKurdistan University of Medical SciencesSanandajIran
  3. 3.Laboratory Technology FacultyKhatam Al-Nabieen UniversityKabulAfghanistan

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