title: Inactive GSK3β is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy.
abstract: Glycogen synthase kinase 3β (GSK3β) is known to control neuroinflammation, however the status of GSK3β in multiple sclerosis, the most common inflammatory demyelinating disease of the CNS, and its animal model EAE, is unknown. In this study, we investigated the expression of phosphorylated GSK3β, the inactive form of GSK3β, in the spinal cords of EAE mice. We demonstrate that while the expression of phosphorylated GSK3β was present in radial astrocytes and neurons of the control mice that received only complete Freund's adjuvant, it was absent in radial astrocytes and significantly lower in neurons of EAE animals. The loss of phosphorylated GSK3β in radial glia and neurons in EAE spinal cords was concurrent with radial glia migration and astrogliosis. This disturbance in the expression of inactive GSK3β was recovered in neurons, but not in the radial glia, after treatment of EAE mice with adipose-derived mesenchymal stem cells capable of inducing a Th2 shift. Collectively, our results suggest a link between inactive GSK3β and modulation of the immune responses during EAE. Thus, we propose that maintenance of GSK3β in its inactive status may play a role in preserving the normal physiology of the spinal cord and amelioration of EAE following stem cell therapy.
authors: Department of Basic Sciences, Faculty of Medical Biotechnology, The National Institute of Genetic Engineering and Biotechnology, Tehran 14965-161, Iran. Electronic address: tafreshi@nigeb.ac.ir.
authors: A Parvaneh
authors: AP
authors: Tafreshi
authors: Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria 3800, Australia.
authors: N
authors: N
authors: Payne
authors: Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria 3800, Australia.
authors: G
authors: G
authors: Sun
authors: Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria 3800, Australia.
authors: A
authors: A
authors: Sylvain
authors: Monash Micro Imaging, Monash University, Melbourne, Victoria, Australia.
authors: K
authors: K
authors: Schulze
authors: Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria 3800, Australia.
authors: C
authors: C
authors: Bernard
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D005620:Freund's Adjuvant; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010766:Phosphorylation; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*
chemical_list: D005620:Freund's Adjuvant; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: EAE; astrogliosis; glycogen synthase kinase β; mesenchymal stem cell therapy; radial glia; spinal cord