IMR Press / JIN / Volume 22 / Issue 2 / DOI: 10.31083/j.jin2202040
Open Access Original Research
Effects of Bone Marrow Mesenchymal Stem Cells on Myelin Repair and Emotional Changes of a Cuprizone-Induced Demyelination Model
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1 Department of Prevention & Healthcare, Southwest Hospital, Third Military Medical University, 400038 Chongqing, China
2 Department of Hepatobiliary & Pancreatic Surgery, The Fifth People's Hospital of Chongqing, 400062 Chongqing, China
3 Department of Neurology, Southwest Hospital, Third Military Medical University, 400038 Chongqing, China
*Correspondence: (Kangning Chen)
J. Integr. Neurosci. 2023, 22(2), 40;
Submitted: 24 August 2022 | Revised: 27 September 2022 | Accepted: 8 October 2022 | Published: 16 February 2023
(This article belongs to the Special Issue Brain Stimulation and Neurodegenerative Diseases)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Multiple sclerosis (MS) is an autoimmune disease for which bone marrow mesenchymal stem cells (BM-MSCs) have become one of the most promising tools for treatment. Cuprizone(CPZ) induces demyelination in the central nervous system and its use has established a demyelination sheath animal model which is particularly suitable for studying the effects of BM-MSCs on the remyelination and mood improvement of a demyelinating model mice. Methods: 70 C57BL/6 male mice were selected and divided into 4 groups: the normal control (n = 20), chronic demyelination (n = 20), myelin repair (n = 15) and cell-treated groups (n = 15). Mice in the normal control group were given a normal diet; the chronic demyelination group mice were given a 0.2% CPZ mixed diet for 14 weeks, mice in the myelin repair and cell-treated groups mice were given a 0.2% CPZ diet for 12 weeks and normal diet for 2 weeks, while the cell-treated group mice were injected with BM-MSCs from the 13th week. The cuprizone-induced demyelination model was successfully established and BM-MSCs extracted, behavioural changes of the mice were detected by open field test, elevated plus maze test and tail suspension test, demyelination and repair of the corpus callosum and astrocyte changes were observed by immunofluorescence and electron microscopy and the concentrations of monoamine neurotransmitters and their metabolites detected by enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemistry (HPLC-ECD). Results: Results suggest BM-MSCs were successfully extracted and cultured, and migrated to the demyelinating area of brain tissue after cell transplantation. Compared with the normal control group, the mice in the chronic demyelination group showed obvious anxiety and depression behaviours (p < 0.05); compared with the chronic demyelination group, the anxiety and depression behaviours of the cell-treated group mice were improved (p < 0.05); compared with the normal control group, the demyelination of the corpus callosum region of the chronic demyelination group mice was significant (p < 0.01), while the myelin sheath of the cell-treated and myelin repair groups was repaired when compared with the chronic demyelination group (p < 0.05), and the cell-treated group had a more significant effect than the myelin repair group (p < 0.05). Compared with the normal control group, the number of astrocytes in the corpus callosum of the chronic demyelination group mice was significantly increased (p < 0.01), and the expression of glial fibrillary acidic protein (GFAP) in the cell-treated group was lower than that in the chronic demyelination and myelin repair groups (p < 0.05); the serum concentrations of norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-Hydroxyindole-3-acetic acid (5-HIAA) between the normal control and the chronic demyelination groups were significantly different (p < 0.05). Conclusions: The CPZ-induced model can be used as an experimental carrier for MS combined with anxiety and depression, and BM-MSC transplantation promotes the repair of myelin sheath and the recovery of emotional disorders in the model.

multiple sclerosis
monoamine neurotransmitters

The demyelination model is successfully induced, and BM-MSCs can promote myelin repair.
The loss of myelin sheath and the repair process may be related to anxiety or depressive behaviour.
The activated astrocytes may promote the loss of myelin sheath and inhibit the regeneration of myelin sheath.
BM-MSCs can partially ameliorate the disorder of monoamine neurotransmitters in demyelination model mice.

SWH2012LC02/Southwest Hospital
Fig. 1.
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