| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pediatrics, Children Research Institute, Medical University of South Carolina, and
* Department of Pathology and Laboratory Medicine, Medical University of South Carolina and Ralph H. Johnson V. A. Medical Center, Charleston, SC 29425, and
Barrow Neurological Institute, Phoenix, Arizona, USA
2Correspondence: Pediatrics Development Neurogenetics, 173 Ashley Avenue, 509 CRI, MUSC, Pediatrics, P.O. Box 250515, Charleston, SC 29425, USA. E-mail: singhi{at}musc.edu
Impaired remyelination due to degeneration of both postmitotic oligodendrocytes and oligodendrocyte progenitors (OPs) is the major hallmark of inflammatory demyelination in multiple sclerosis (MS) lesions and experimental autoimmune encephalomyelitis (EAE). Here, we have demonstrated the potential of lovastatin, a HMG-CoA reductase inhibitor, for the restoration of impaired remyelination mediated through enhanced survival and differentiation of OPs in the spinal cord of treated EAE animals. Lovastatin treatment significantly increased the level of myelin lipids in the spinal cord of treated EAE animals, coinciding with the attenuation of disease severity and inflammatory demyelination as compared with untreated EAE animals. The increased expression of myelin proteins and transcription factors associated with differentiating oligodendrocytes along with the increase in number of NG2+/BrdU– and NG2+/BrdU+ cells, and the expression of proliferating OP-specific proteins, demonstrated the restoration of remyelination in the spinal cord of lovastatin-treated EAE animals. Corresponding to this, in vitro studies further corroborated the increased survival and differentiation of OPs in lovastatin-treated activated mixed glial cells suggesting that lovastatin protects against the degeneration of OPs and enhances their differentiation through induction of a pro-remyelinating environment in the spinal cord of treated EAE animals. Together, these data demonstrate that lovastatin has the potential to augment remyelination in MS lesions and other neuroinflammatory diseases.— Paintlia, A. S., Paintlia, M. K., Khan, M., Vollmer, T., Singh, A. K., Singh, I. HMG-CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis.
Key Words: lovastatin • oligodendrocyte progenitors • spinal cord • encephalomyelitis • multiple sclerosis • remyelination
This article has been cited by other articles:
|
|
 |
|
  A. S. Paintlia, M. K. Paintlia, A. K. Singh, and I. Singh Inhibition of Rho Family Functions by Lovastatin Promotes Myelin Repair in Ameliorating Experimental Autoimmune Encephalomyelitis Mol. Pharmacol., May 1, 2008; 73(5): 1381 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Paintlia, M. K. Paintlia, I. Singh, and A. K. Singh Immunomodulatory Effect of Combination Therapy with Lovastatin and 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside Alleviates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Am. J. Pathol., September 1, 2006; 169(3): 1012 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Paintlia, M. K. Paintlia, I. Singh, and A. K. Singh IL-4-Induced Peroxisome Proliferator-Activated Receptor {gamma} Activation Inhibits NF-{kappa}B Trans Activation in Central Nervous System (CNS) Glial Cells and Protects Oligodendrocyte Progenitors under Neuroinflammatory Disease Conditions: Implication for CNS-Demyelinating Diseases J. Immunol., April 1, 2006; 176(7): 4385 - 4398. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
