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Upregulation of CSPG3 Accompanies Neuronal Progenitor Proliferation and Migration in EAE

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Abstract

The molecular identities of signals that regulate the CNS lesion remodeling remain unclear. Herein, we report for the first time that extracellular matrix chondroitin sulphate proteoglycan, CSPG3 (neurocan) is upregulated after primary inflammatory injury. EAE was induced using myelin oligodendrocyte glycoprotein (MOG) (35–55) which was characterized by massive polymorphonuclear cell infiltration and loss of myelin basic protein expression along with steep decrease of CNPase. Periventricular white matter (PVWM) and cortex presented with astrogliosis evidenced by increased Glial fibrillary acidic protein (GFAP) immunoreactivity 20 days post immunization (p.i). Neuronal progenitor cell (NPC) proliferation increased after first acute episode in the subventricular zone (SVZ), corpus callosum, and cortex, indicating migration of cells to structures other than rostral migration stream and olfactory bulb, which is indicative of cell recruitment for repair process and was confirmed by presence of thin myelin sheaths in the shadow plaques. Earlier CSPG3 has been demonstrated to impede regeneration. We observed neuroinflammation-induced up-regulation of the CSPG3 expression in two most affected regions viz. PVWM and cortex after proliferation and migration of NPCs. Our results show possible role of reactive astrogliosis in lesion remodeling and redefine the relation between inflammation and endogenous cellular repair which can aid in designing of newer therapeutic strategies.

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Acknowledgement

Authors are thankful to Dr. G.N Qazi (Vice Chancellor, Jamia Hamdard) for moral support during the study. Authors express sincere thanks to Dr. Mir Sadaqat, Department of Internal Medicine—SKIMS Medical College Hospital, Srinagar-India for his kind help in GFAP immunohistochemistry.

Mir Sajad is recipient of Senior Research Fellowship (SRF) from Ministry of Health and Family Welfare, Govt. of India, New Delhi.

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Authors and Affiliations

  1. Developmental Toxicology Laboratory, Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110062, India

    Mir Sajad, Jamil Zargan, Sadiq Umar & Haider A. Khan

  2. Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences (INMAS) DRDO, New Delhi, 110054, India

    Raman Chawla

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  1. Mir Sajad
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  2. Jamil Zargan
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Correspondence to Haider A. Khan.

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Sajad, M., Zargan, J., Chawla, R. et al. Upregulation of CSPG3 Accompanies Neuronal Progenitor Proliferation and Migration in EAE. J Mol Neurosci 43, 531–540 (2011). https://doi.org/10.1007/s12031-010-9476-0

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  • DOI: https://doi.org/10.1007/s12031-010-9476-0

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