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

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.

[1]  M. Safari,et al.  G-CSF for mobilizing transplanted bone marrow stem cells in rat model of Parkinson’s disease , 2016, Iranian journal of basic medical sciences.

[2]  M. Safari,et al.  Mesenchymal stem cells that located in the electromagnetic fields improves rat model of Parkinson’s disease , 2016, Iranian journal of basic medical sciences.

[3]  M. Safari,et al.  Protective Effects of Water Extract of Propolis on Dopaminergic Neurons, Brain Derived Neurotrophic Factor and Stress Oxidative Factors in the Rat Model of Parkinson’s Disease , 2015 .

[4]  A. Elbana,et al.  Endogenous bone marrow stem cell mobilization in rats: Its potential role in homing and repair of damaged inner ear , 2015 .

[5]  R. F. Hoyt,et al.  Regulatory T cells enhance mesenchymal stem cell survival and proliferation following autologous cotransplantation in ischemic myocardium. , 2014, The Journal of thoracic and cardiovascular surgery.

[6]  A. Glavaski-Joksimovic,et al.  Mesenchymal stem cells and neuroregeneration in Parkinson's disease , 2013, Experimental Neurology.

[7]  S. Chae,et al.  Effect of caffeic acid phenethyl ester (CAPE) on H₂O₂ induced oxidative and inflammatory responses in human middle ear epithelial cells. , 2012, International journal of pediatric otorhinolaryngology.

[8]  Daniel J. Maltman,et al.  Role of mesenchymal stem cells in neurogenesis and nervous system repair , 2011, Neurochemistry International.

[9]  R. Dodel,et al.  Caffeic acid phenethyl ester prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration , 2011, Neuroscience.

[10]  Rong Zeng,et al.  Differentiation of Human Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells In Vitro , 2011, Spine.

[11]  K. Sugaya,et al.  Stem cells for the treatment of neurodegenerative diseases , 2010, Stem Cell Research & Therapy.

[12]  J. Fischer,et al.  Cell therapy in bone healing disorders , 2010, Orthopedic reviews.

[13]  C. Teng,et al.  Stem Cells for the Treatment of Neurodegenerative Diseases , 2010, Molecules.

[14]  L. Lanfumey,et al.  Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson’s Disease , 2010, Neurotoxicity Research.

[15]  R. Prediger,et al.  The risk is in the air: Intranasal administration of MPTP to rats reproducing clinical features of Parkinson's disease , 2006, Experimental Neurology.

[16]  Hansjürgen Bratzke,et al.  Stages in the development of Parkinson’s disease-related pathology , 2004, Cell and Tissue Research.

[17]  T. Robbins,et al.  l-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease , 2003, Neuropsychologia.

[18]  W. Dauer,et al.  Parkinson's Disease Mechanisms and Models , 2003, Neuron.

[19]  N. Pellegrini,et al.  Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. , 2003, The Journal of nutrition.

[20]  A. Russo,et al.  Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. , 2002, Fitoterapia.

[21]  M. Chopp,et al.  Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease , 2001, Neuroscience Letters.

[22]  Joseph P Huston,et al.  Behavioral phenotyping of the MPTP mouse model of Parkinson's disease , 2001, Behavioural Brain Research.

[23]  O. Mirzoeva,et al.  Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties , 1993, FEBS letters.

[24]  P. Mcgeer,et al.  The Role of Anti-Inflammatory Agents in Parkinson’s Disease , 2007, CNS drugs.

[25]  P. Mcgeer,et al.  Inflammation in Parkinson's disease. , 2001, Advances in neurology.

[26]  W. Hall,et al.  A rat model of Parkinson's disease induced by Japanese encephalitis virus. , 1997, Journal of neurovirology.