Neurological functional recovery after thymosin beta4 treatment in mice with experimental auto encephalomyelitis

Abstract

In the present study, we hypothesized that thymosin beta 4 (Tbeta4) is a potential therapy of multiple sclerosis (MS). To test this hypothesis, SJL/J mice (n=21) were subjected to experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE mice were treated with saline or Tbeta4 (6 mg/kg, n=10) every 3 days starting on the day of myelin proteolipid protein immunization for total 5 doses. Neurological function, inflammatory infiltration, oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes were measured in the brain of EAE mice. Double immunohistochemical staining was used to detect proliferation and differentiation of OPCs. Tbeta4 was used to treat N20.1 cells (premature oligodendrocyte cell line) in vitro, and proliferation of N20.1 cells was measured by bromodeoxyuridine (BrdU) immunostaining. Tbeta4 treatment improved functional recovery after EAE. Inflammatory infiltrates were significantly reduced in the Tbeta4 treatment group compared to the saline groups (3.6±0.3/slide vs 5±0.5/slide, p<0.05). NG2 + OPCs (447.7±41.9/mm 2 vs 195.2±31/mm 2 in subventricular zone, 75.1±4.7/mm 2 vs 41.7±3.2/ mm 2 in white matter), CNPase + mature oligodendrocytes (267.5±10.3/mm 2 vs 141.4±22.9/ mm 2 ), BrdU + with NG2 + OPCs (32.9±3.7/mm 2 vs 17.9±3.6/mm 2 ), BrdU + with CNPase + mature oligodendrocytes (18.2±1.7/mm 2 vs 10.7±2.2/mm 2 ) were significantly increased in the Tbeta4 treated mice compared to those of saline controls (p<0.05). These data indicate that Tbeta4 treatment improved functional recovery after EAE, possibly, via reducing inflammatory infiltrates, and stimulating oligodendrogenesis.

Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

“…We previously demonstrated a strong association of T␤4 treatment with OL differentiation in in vivo and in in vitro models (5)(6)(7)23). The results of this study further support our central hypothesis of T␤4-mediated oligodendrogenesis.…”

“…In addition, T␤4 promotes cardiomyocyte and keratinocyte migration in these models. T␤4 improves functional outcome after experimental induction of multiple sclerosis, embolic stroke, and traumatic brain injury (5)(6)(7). In all three models, improvement in neurological outcome is associated with oligodendrogenesis (i.e.…”

Expression of thymosin β4 in odontoblasts during mouse tooth development

“…Tβ4 mRNA and BrdU are strongly expressed in the same cells of the oral epithelium and tooth bud on E10.5 during the initial stage and on E13 and E14 during the bud stage (16,19). Treatment of Tβ4 increases the proliferation of embryonic endothelial cells in mouse and oligodendrocytes in encephalomyelitis compared to a control group (20,21). In this study, Tβ4 protein was strongly expressed in the oral epithelium and tooth bud during the bud stage.…”

Roles of NG2 glial cells in diseases of the central nervous system

“…On the one hand, lovastatin (HMG-CoA reductase inhibitor) [40] , glamorgan acetate [41] , guanosine or guanine [42] , ciliary neurotrophic factor [43] , thymosin β4 [44] , and endogenous leukemia inhibitory factor [45] , through different cascades of signal transduction, increase the numbers of NG2 cells and oligodendrocytes, and put an end to the demyelination process. The expression of platelet-derived growth factor α receptors (PDGFαRs) increases during the proliferation of NG2 cells, and NG2 proteoglycan expression disappears as NG2 cells differentiate into mature oligodendrocytes [46] .…”