Protective Effect of Curcumin on Neural Myelin Sheaths by Attenuating Interactions between the Endoplasmic Reticulum and Mitochondria after Compressed Spinal Cord

Hai Jun Yu,Lan Ma

doi:10.4172/2165-7939.1000322

Abstract

Oligodendrocyte apoptosis is the leading cause of demyelination in the central nervous system after compressed spinal cord injury (CSCI). Curcumin, which belongs to the curcuminoid family, is a phenolic yellow pigment derived from the powdered rhizome of Curcuma longa. It has been proved that curcumin exhibits neuroprotective effects against traumatic spinal cord injury by inhibiting neuronal apoptosis. However, whether curcumin has a protective effect on demyelination after CSCI by inhibiting the apoptosis of oligodendrocytes has not been reported. Therefore this study was designed to investigate whether curcumin has a reparative effect on CSCI-induced demyelination and, if so, how it does so. First, we found that the administration of 100 mg/kg curcumin intraperitoneally (IP) 60 minutes after CSCI at days 1, 3, and 7 could significantly relieve neurological deficits. After staining with osmic acid, we found that the swelling of myelin sheaths in the treated group was milder than that in the vehicle group. The results of luxol fast blue staining also indicated that the number of remaining myelin sheaths was significantly higher in the treated group. Next we detected the expressions of active caspase-3, caspase-12, cytochrome C, and myelin basic protein (MBP) by Western blot. This revealed that the expression of MBP was significantly enhanced in the curcumin-treated group, consistent with the number of remaining myelin sheaths found on luxol fast blue staining. But the expression of caspase-12, cytochrome C, and active caspase-3 was reduced; in addition, double immunofluorescence showed that active caspase-3–positive oligodendrocytes in the treatment group were fewer in number as compared with the vehicle group. These results suggested that curcumin did have a protective effect on demyelination—mainly through its mediating effects on the endoplasmic reticulum–mitochondrial pathway—to significantly reduce the expression of active caspase-3. In this way cucurmin reduced both the apoptosis of oligodendrocytes and demyelination, thus ameliorating the consequences of CSCI.

Highlights

Compressed spinal cord injury (CSCI), which has drawn global attention owing to its increasing incidence, is caused by vertebral fracture, rigidification of the ligamenta flava, bone marrow tumor, ossification of the posterior longitudinal ligament, epidural hematoma, disk protrusion, and so on [1,2]
To determine whether curcumin has a protective effect on axonal myelinated after CSCI, we used osmic acid and luxol fast blue (LFB) staining to Citation: Yu HJ, Ma L, Jiang J, Sun SQ (2016) Protective Effect of Curcumin on Neural Myelin Sheaths by Attenuating Interactions between the Endoplasmic Reticulum and Mitochondria after Compressed Spinal Cord
To investigate the effect of cucumin and its possible mechanism of action on oligodendrocyte apoptosis, we examined endoplasmic reticulum stress by evaluating caspase-12, which responds to such stress and mitochondrial dysfunction by detecting cytochrome C, which indicates enhancement of mitochondrial membrane’s permeability [1]

Summary

Introduction

Compressed spinal cord injury (CSCI), which has drawn global attention owing to its increasing incidence, is caused by vertebral fracture, rigidification of the ligamenta flava, bone marrow tumor, ossification of the posterior longitudinal ligament, epidural hematoma, disk protrusion, and so on [1,2]. Stem cell therapy, which is one method of cellular transplantation, has facilitated recovery in animal models following SCI [6,7] Such treatment poses problems in clinical application owing to its complex technology and high cost; research aimed at improving functional recovery after SCI has focused on searching for new drugs, screening them, and exploiting their potential [8,9]. Oligodendrocytes responses to ischemic and anoxic insults occur earlier than those of nerve cells Both neurons and oligodendrocytes undergo apoptosis at the lesion site 8 hours after SCI; between 24 hours and 14 days, only apoptotic oligodendrocytes are found at the injury site; these spread several millimeters caudally and rostrally away from the lesion’s center [19]. The aim of the current study has been to determine whether curcumin can decrease the apoptosis of oligodendrocytes and protect myelinated nerve fibers from CSCI-triggered demyelination.

Experimental Procedures

Results

Discussion

Conclusion