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. 2022 Sep-Oct;13(5):637-646.
doi: 10.32598/bcn.2021.1398.1. Epub 2022 Sep 1.

Caffeic Acid Phenethyl Ester With Mesenchymal Stem Cells Improves Behavioral and Histopathological Changes in the Rat Model of Parkinson Disease

Khojasteh Rahimi Jaberi  1 , Manouchehr Safari  1 , Vahid Semnani  2 , Hamid Reza Sameni  1 , Sam Zarbakhsh  1 , Laya Ghahari  3
Affiliations

Caffeic Acid Phenethyl Ester With Mesenchymal Stem Cells Improves Behavioral and Histopathological Changes in the Rat Model of Parkinson Disease

Khojasteh Rahimi Jaberi et al. Basic Clin Neurosci. 2022 Sep-Oct.

Abstract

Introduction: Parkinson disease (PD) results from the destruction of dopaminergic neurons in the brain. This study aimed to investigate the protective effects of natural antioxidants such as caffeic acid phenethyl ester (CAPE) to maintain these neurons.

Methods: CAPE is one of the main ingredients of propolis. Intranasal administration of 1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine (MPTP) was used to generate a PD model in rats. A total of 2×bone marrow stem cells (BMSCs) were injected from the tail vein. Behavioral tests, immunohistochemistry, DiI, cresyl fast violet, and TUNEL staining were used to evaluate the rats 2 weeks after treatment.

Results: In all treatment groups with stem cells, the DiI staining method revealed that the cells migrated to the substantia nigra pars compacta after injection. Treatment with CAPE significantly protects dopaminergic neurons from MPTP. The highest number of tyrosine hydroxylase (TH) positive neurons was seen in the pre-CAPE+PD+stem cell (administration of CAPE, then the creation of PD, finally injection of stem cells) group. The number of TH+cells in all groups that received CAPE was significant compared to groups that received the stem cells only (P<0.001). Intranasal administration of MPTP significantly increases the number of apoptotic cells. The lowest number of apoptotic cells was in the CAPE+PD+stem cell group.

Conclusion: The results showed that the use of CAPE and stem cells in Parkinson rats caused a significant reduction in the apoptotic cells.

Keywords: Antioxidant; Caffeic acid phenethyl ester; MPTP; Parkinson disease; TUNNEL staining.

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Conflict of interest statement

Conflict of interest The authors declared no competing interest.

Figures

Figure 1.
Figure 1.
Improving behavioral pole test before and after treatment with Caffeic Acid Phenethyl Ester (CAPE) One-way ANOVA and Tukey post hoc test (n=7) showed that behavioral improvement was significantly higher in pre-treatment with CAPE groups than in other treatment groups. All values are Mean±SEM. *P≤0.001compared with the MPTP (1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine) (PD) group.
Figure 2.
Figure 2.
Migration of injected cells to the damaged area of the Substantia Nigra Pars Compacta (SNpc) Arrows represent Bone Marrow Stem Cells (BMSCs) (2×106) labeled with DiI in the substantia nigra of the mid-brain in rats (×20: Scale bar 400 μm, 40× magnification: scale bar 20 μm). The results show that in the pre-CAPE+PD+stem cells treatment group, the number of stained cells with DiI is higher than in other treatment groups. The images were at 20× and 40× magnifications.
Figure 3.
Figure 3.
Caffeic Acid Phenethyl Ester (CAPE) increasing the number of dopamine-positive cells in the Substantia Nigra Pars Compacta (SNpc) One-way ANOVA and Tukey post hoc test (n=7) showed that the number of tyrosine hydroxylase positive neurons in the pretreatment treatment group increased significantly and decreased significantly in the Parkinson group compared to the other groups. All values are Mean±SEM. * P≤ 0.001 compared with the MPTP (1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine) (PD) group.
Figure 4.
Figure 4.
Caffeic acid phenethyl ester (CAPE) and bone marrow stem cells (BMSCs) increasing the number of dopamine-positive cells in the Substantia Nigra Pars Compacta (SNpc) Immunohistochemical images showed that using CAPE before PD could significantly protect dopamine-secreting neurons. Also, in the groups that received CAPE or stem cells separately after PD, there was no significant difference in the number of positive dopamine-secreting neurons. The squares in all the pictures show the border of the SNpc. Groups in figures included A: PD group, B: PD plus stem cell, C: Pre-CAPE plus PD, D: Pre-CAPE+PD+stem cell, E: PD+Stem cell+CAPE, and F: PD+CAPE. The images were at a 20×magnification. The results were evaluated using the 1-way ANOVA and the Tukey post hoc (n=7).
Figure 5.
Figure 5.
Caffeic acid phenethyl ester (CAPE) reducing the number of apoptotic cells in substantia nigra pars compacta (SNpc) The results of 1-way ANOVA and Tukey post hoc test (n=7). The results showed that in the pretreatment groups with CAPE alone or with stem cells, the number of apoptotic cells will be significantly reduced. In other treatment groups, although there is a decrease in apoptotic cells, there is no significant difference with the Parkinson group. * P≤0.001 compared with the MPTP (1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine) (PD) group.
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