Sobhan Haghani, Nida Jamali-Raeufy, Motahareh Zeinivand, Soraya Mehrabi, Leila Aryan, Javad Fahanik-Babaei,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Although pharmacotherapy is the most common treatment for epilepsy, proper seizure control is not achieved with current medications. This study evaluated the protective effects of the Hepatocyte Growth Factor (HGF) in a rat model of Temporal Lobe Epilepsy (TLE) and explored possible molecular mechanisms.
Methods: A TLE rat model was determined using an intra-hippocampal kainic acid injection (4 μg). Intra-cerebrovascular injection of HGF (6 μg) was performed 30 min before kainic acid injection. Learning and memory impairment were investigated by behavioral tests. The Enzyme-Linked Immunosorbent (ELISA) was used to determine astrogliosis and DNA fragmentation. Changes in neuronal density and mossy fiber sprouting were evaluated by Nissl and Timm staining, respectively.
Results: Behavioral assessments indicated that kainate-treated rats presented spontaneous seizures. Moreover, their alternation percentage scores in the Y-Maze test were lower (P<0.001). Likewise, the passive avoidance test confirmed learning disability in Kainate-treated rats (P<0.001). HGF administration reduced the number of spontaneous seizures, alternation percentage score (P<0.001), and cognitive disturbances (P<0.001). The histopathological results also showed that a protected HGF administration contributed to the reduction of neuronal loss in the CA3 subregion of the hippocampus and inhibited the formation of aberrant Mossy Fiber Sprouting (MFS) (P<0.01). Furthermore, the ELISA data indicated a significant decrease in GFAP (P<0.01) and DNA fragmentation (P<0.05) following HGF administration.
Conclusion: Our findings demonstrated the validity of HGF in protection against the progression of the kainate-induced TLE in rats. This measure improved learning, cognitive disturbances and inhibited apoptosis and astrogliosis.
Farshid Saadat, Zohreh Zareighane, Farnaz Safavifar, Seyedeh Zohreh Jalali, Azar Berahmeh, Mohammad Reza Khorramizadeh,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Glioblastoma is an aggressive human brain malignancy with poorly understood pathogenesis. Voltage-gated potassium (Kv) channels and Matrix Metalloproteinases (MMPs) are highly expressed in malignant tumors and involved in the progression and metastasis of glioblastoma. This study aimed to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell involved in the immunopathogenesis of glioblastoma.
Methods: The cytotoxic effect of 4-Aminopyridine (4-AP) at different doses in the cell model of glioblastoma was measured by MTT assay. The ELISA technique and gelatin zymography were used to assess cytokine levels and MMP-9 after 4-AP treatment.
Results: Cytotoxicity analysis data indicated that cell viability reduced by increasing 4-AP level and cell growth decreased gradually by removing 4-AP from the cell medium. 4-AP inhibits the secretion of IL-6 and IL-1 (P<0.05). MMP9 activity significantly inhibits with increased 4-AP dose, compared to non-treated cells.
Conclusion: The reduction of cell viability, IL-6 secretion, and MMP-9 activity in an in vitro model of glioblastoma might be assumed 4-AP as an agent for chemoprevention of cancer.
Grace Akingbade, Omamuyovwi Ijomone, Sunday Adelakun, Bernard Enaibe,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Prenatal exposure to Marijuana (MJN) has been associated with various brain deficits. The main activity in marijuana, Δ9-Tetrahydrocannabinol (THC), crosses the placenta and affects fetal brain development. Despite this, marijuana remains a commonly abused substance among pregnant women. The current study examined the histological and biochemical changes in the Superior Colliculus (SC) and Lateral Geniculate Nucleus (LGN) in rat brains prenatally exposed to marijuana.
Methods: Four groups of pregnant rats (n=5 rats/group) were exposed to the smoke of 10 g/kg marijuana at various days during their gestational period, with a group (control), i.e., not exposed. After parturition, the litters from each group were sacrificed by cervical dislocation on postnatal days 7, 14, and 21; the superior colliculi and lateral geniculate nuclei were excised. Tissue sections were prepared for histological studies using Haematoxylin and Eosin stains. Biochemical studies were performed on alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activity levels. The histological and biochemical analyses of tissues were performed.
Results: Prenatal exposure to marijuana resulted in spontaneous abortion and affected neuronal morphology in the SC and LGN of the progeny. Furthermore, the levels of enzyme activities were altered following maternal exposure to MJN.
Conclusion: These data suggested that histological changes in the SC and LGN were associated with oxidative damage.
Soheila Pourkhodadad, Shahrbanoo Oryan, Mohammad Mehdi Hadipour, Gholamreza Kaka, Seyed Homayoon Sadraie,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Spinal Cord Injury (SCI) is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss, and severe functional deficits. Neurotrophic factors are a potential treatment for reducing secondary damage, promoting axon growth; they are responsible for inducing myelination after injury. Olfactory Ensheathing Cells (OECs) and minocycline have promoted locomotor function after SCI. The present study investigated the neuroprotective effects of combined treatment with minocycline and OECs on spinal cord injury related to Brain-Derived Neurotrophic Factor (BDNF) and Glial Derived Neurotrophic Factor (GDNF) expressions after SCI.
Methods: Adult female rats were used to experimental SCI by weight compression method. Rats received an intraperitoneal minocycline injection (90 mg/kg) immediately after SCI and 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and Electromyography (EMG). After 5 weeks, the spinal cord segment centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF, and Myelin Basic Protein (MBP).
Results: SCI induced the loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline+OECs increased the score of the BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results suggested that NeuN expression significantly increased in the minocycline+OECs group than other groups. Moreover, electromyography amplitude in treated rats was increased compared to the control group. BDNF, GDNF, and MBP expressions and the number of ventral motor neurons increased further by minocycline+OECs in SCI rats.
Conclusion: The present study provides evidence that minocycline may facilitate recovery of locomotor function by OECs by increasing BDNF and GDNF expressions following SCI.
Forogh Zakernezhad, Mahmood Barati, Nima Sanadgol, Monireh Movahhedi, Ahmad Majd, Fereshteh Golab,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Obesity is among the most severe challenges of our era, with significant health consequences and a high economic burden for health systems. Therefore, many countries have developed political agendas to cope with this ever-rising challenge. Along with chemical medications developed to manage obesity, researchers have focused on some natural ingredients and herbal extracts that are effective in reducing weight. The current study investigated the association between Foeniculum vulgar (fennel) extracts and body weight, lipid profile, and leptin.
Methods: In total, 35 adult male BALB/c mice were investigated in sham, fennel 50 mg/kg, fennel 100 mg/kg, and fennel 200 mg/kg (n=7) groups. The mice were administered fennel extracts for fourteen days while weighted at the intervention’s beginning and end. Then, their weight, lipid profile, serum leptin, and expression of leptin protein in the hypothalamus were measured.
Results: After providing the intervention, leptin receptor protein expression was increased in all groups, while serum leptin didn’t change significantly. Moreover, a significant decrease was observed in the cholesterol dose of 100 mg/kg/day, triglycerides in 100 and 200 mg/kg/day, and LDL in 50 and 100 mg/kg/day. Serum HDL was increased significantly in a dose of 100 mg/kg/day.
Conclusion: Fennel extract can decrease the lipid profile by changing the expression of the leptin receptor.
Hossein Soltaninejad, Mehdi Alizadeh Zarei, Malahat Akbarfahimi, Akram Azad, Farzad Rabiei,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Activities of Daily Living (ADL), as an ultimate goal of rehabilitation, rely on cultural and environmental factors. This study aimed to develop a questionnaire based on the occupational therapy practice frame to accurately evaluate Iranian children’s occupational performance.
Methods: This scale was developed in two phases of planning and construction. The planning phase involved a literature review and a collection of the available evaluation tools in the area. The advice of two expert panels was used to develop a preliminary 87-item questionnaire. In the construction phase, 40 parents were surveyed to assess the popularity of the activities in Iran. After a face to content validation, the final version of the questionnaire was prepared with 93 items.
Results: The final 93-item questionnaire was used to assess the ADL of 3-6-year-old children. The 93 items, selected according to criteria found in the literature and the panel of experts, were categorized into six ranges of occupational therapy practice framework (bathing/washing/personal hygiene, toileting, dressing, eating/feeding, functional mobility, and others).
Conclusion: The ADL in Iranian children is a practical and culturally relevant tool for measuring the occupational performance of Iranian children. It can be used in clinical and population-based research.
Seyed Abdollah Samani, Mohammad Raman Moloudi, Rashid Ramezanzadeh, Mohammad Abdi, Bahram Nikkhoo, Esmael Izadpanah, Daem Roshani, Alina Abdolahi, Parisa Esmaili, Kambiz Hassanzadeh,
Volume 13, Issue 1 (1-2022)
Abstract
Introduction: Probiotics, including lactobacilli, have immunomodulatory activities with promising effects on inflammatory diseases. In this study, we evaluate the effect of Enterococcus durans (Edu) and three various strains of lactobacilli (Lacto-mix), including L. rhamnosus, L. casei, and L. plantarum, to prevent Experimental Autoimmune Encephalomyelitis (EAE) features
Methods: C57BL/6 female mice were inoculated with Myelin Oigodendrocyte Glycoprotein (MOG35-55) in CFA (complete Freund’s adjuvant) to induce EAE. Five groups (n=6 in each group) of animals received saline or probiotics by oral gavage with 200 µL of lactobacilli (1.5×108 CFU/mL) for 2 weeks before the immunization and during the test for one month.
Results: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in inflammatory cells in the probiotic-treated animals. Pro-inflammatory cytokines (Interleukin [IL]-17 and Interferon [IFN]-γ) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (P<0.01). While in the spinal cord tissue, there was a decrease in IL-17 in those animals treated with the Lacto-mix and Edu + Lacto-mix (P<0.01) and a significant decrease in IFN-γ in those animals that received Edu (P<0.05). Western blot analysis of matrix metalloproteinase-9 and myelin basic protein showed a decrease and increase in treatment and EAE groups, respectively, compared to the normal control group.
Conclusion: Our data suggest that probiotic Enterococcus durans and Lacto-mix prevents EAE, but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials.
Leila Beigom Hejazian, Zeinab Akbarnejad, Fatemeh Moghani Ghoroghi, Banafshe Esmaeilzade, Samira Chaibakhsh,
Volume 13, Issue 1 (1-2022)
Abstract
Introduction: Cell therapy is the most advanced treatment of peripheral nerve injury. This study aimed to determine the effects of transplantation of hair follicle stem cells on the regeneration of the sciatic nerve injury in rats.
Methods: The bulge region of the rat whisker were isolated and cultured. Morphological and biological features of the cultured bulge cells were observed by light microscopy and immunocytochemistry methods. Percentages of CD34, K15, and nestin cell markers expression were demonstrated by flow cytometry. Rats were randomly divided into 3 groups of injury, epineurium, and epineurium with cells in which rat Hair Follicular Stem Cells (rHFSCs) were injected into the site of the nerve cut. HFSCs were labeled with Bromodeoxyuridine (BrdU), and double-labeling immunofluorescence was performed to study the survival and differentiation of the grafted cells. After 8 weeks, electrophysiological, histological, and immunocytochemical analysis assessments were performed.
Results: Rat hair follicle stem cells are suitable for cell culture, proliferation, and differentiation. The results suggest that transplantation of rat hair follicle stem cells can regenerate sciatic nerve injury; moreover, electrophysiology and histology examinations show that sciatic nerve repair was more effective in the epineurium with cell group than in the other experimental group (P<0.05).
Conclusion: The achieved results propose that hair follicle stem cells improve axonal growth and functional recovery after peripheral nerve injury.
Abolfazl Alipour, Gholamreza Hatam, Hassan Seradj,
Volume 13, Issue 1 (1-2022)
Abstract
Introduction: Information processing in microtubules is an open question that has not been adequately addressed. It was suggested that microtubules could store and process information in the nervous system or even support consciousness. The unicellular organism, Paramecium caudatum, has a microtubular structure but lacks a neuron or neural network. However, it shows intelligent behaviors such as associative learning. This property may suggest that the microtubules are involved in intelligent behavior, information storage, or information processing in this organism.
Methods: To test this hypothesis and study the role of microtubules in P. caudatum learning, we utilized a learning task in which the organism associates brightness in its swimming medium with attractive cathodal shocks. To see if microtubules are an integral part of information storage and processing in P. caudatum, we disrupted the microtubular dynamics in the organism using an antimicrotubular agent (parbendazole).
Results: We observed that while a partial allosteric modulator of GABA (midazolam) could disrupt the learning process in P. caudatum, the antimicrotubular agent could not interfere with the learning.
Conclusion: Microtubules are probably not vital for the learning behavior in P. caudatum. Consequently, our results call for further investigation of the microtubular information processing hypothesis.
Sehar Mobasseri, Arash Javeri, Masoumeh Fakhr Taha,
Volume 13, Issue 2 (3-2022)
Abstract
Introduction: The extract of pluripotent stem cells induces dedifferentiation of somatic cells with restricted plasticity.
Methods: In this study, we used the extract of human embryonic stem cells (hESC) to dedifferentiate adipose tissue-derived stem cells (ADSCs) and examined the impact of this reprogramming event on the dopaminergic differentiation of the cells. For this purpose, cytoplasmic extract of ESCs was prepared by repeated freezing and thawing cycles. The plasma membrane of hADSCs was reversibly permeabilized by streptolysin O (SLO), exposed to hESC extract, and resealed by a CaCl2-containing medium.
Results: As revealed by qPCR analysis, expression of OCT4, SOX2, NANOG, LIN28A, and KLF4 mRNAs were downregulated in the ADSCs one week after extract incubation, while all mRNAs except for KLF4 were upregulated at the end of the second week. For dopaminergic differentiation, control and reprogrammed ADSCs were induced by a serum-free neurobasal medium containing B27 and a cocktail of sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), fibroblastic growth factor 8 (FGF8), and brain-derived neurotrophic factor (BDNF) for 12 days. After differentiation, the expression levels of some neuronal and dopaminergic-related genes, including PAX6, NESTIN, NEFL, GLI1, LMXB1, EN1, NURR1, and TH, significantly increased in the reprogrammed ADSCs compared to the control group. On the whole, two weeks after reprogramming by ESC extract, ADSCs showed an improved dopaminergic differentiation potential.
Conclusion: These findings suggest that the cytoplasmic extract of hESCs contains some regulatory factors which induce the expression of pluripotency-associated markers in somatic cells and that the exposure to ESC extract may serve as a simple and rapid strategy to enhance the plasticity of somatic stem cells for cell replacement therapy purposes.
Zohreh Bagheri, Fatemeh Shamsi, Zahra Zeraatpisheh, Mahin Salmannejad, Ahmad Soltani, Hadi Aligholi,
Volume 13, Issue 2 (3-2022)
Abstract
Introduction: The present study addressed whether methylprednisolone (MP) as an anti-inflammatory drug used in neurodegenerative diseases and neural stem/progenitor cells (NS/PCs) is safe.
Methods: First, embryonic rat NS/PCs were exposed to different concentrations of MP, and then we evaluated their survival by MTT assay, proliferation by analyzing the number and diameter of neurospheres, and the migration of the cells by neurosphere assay.
Results: The viability of NS/PCs was reduced following exposure to 10, 15, and 20 µg/mL of MP. In addition, although the number of neurospheres did not change, exposure to different concentrations of MP resulted in the formation of smaller neurospheres. Despite these undesirable effects, the highest concentration of MP (20 μg/mL) increased the migration capacity of the NS/PCs.
Conclusion: The combination of MP and NS/PCs is not recommended due to the adverse effects of MP on the survival and proliferation of NS/PCs.
Neda Ghadamgahi Sani, Malahat Akbarfahimi, Shadi Akbari, Mehdi Alizadeh Zarei, Ghorban Taghizadeh,
Volume 13, Issue 2 (3-2022)
Abstract
Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders characterized by poor attention and subsequently lower learning abilities than normal children. This study aimed to compare the effectiveness of neurofeedback and perceptual-motor exercises as two common nonpharmacological treatments for visual attention.
Methods: A total of 40 combined medicated ADHD children (aged 5-12 years) were randomly allocated into two groups: neurofeedback training and perceptual-motor exercises. Visual attention and motor proficiency were assessed before and after the treatment by continuous performance test (CPT) and Bruininks-Oseretsky Test (BOT), respectively.
Results: According to repeated measures analysis of variance (ANOVA), both groups showed significant improvement in three attention-related areas of CPT, including reaction time, omission, and commission errors (P<0.001), while the difference between the two groups was not significant (P>0.05). However, in the perceptual-motor exercises group, motor proficiency improved significantly (P<0.01).
Conclusion: Neurofeedback training intervention, as well as perceptual-motor exercises, are effective in improving ADHD symptoms, and given the similar effect of both interventions and their lack of side effects, perceptual-motor exercises appear to be the more appropriate option for reducing symptoms of ADHD, because of its additional effect on motor proficiency, rich content of purposeful activities, and social interactions.
Negar Noorbakhsh, Hamid Galehdari, Mohammad Shafiei,
Volume 13, Issue 3 (5-2022)
Abstract
Introduction: Sialic acid is pivotal in various critical physiological events at molecular and cellular levels and pathological processes. Changes in sialic acid concentration are observed in many pathological processes; for example, some available data exist on the evaluated level of sialic acid and neurodegenerative prevalence. Presumably, sialic acid can play a significant role in regulating a diverse range of uncovered neurodegeneration factors and downstream targets. matrix metalloproteinases 9 (MMP9) is one factor that changes the exposure of different concentrations of sialic acid solution. Hence, we aimed to examine the possible effect of sialic acid solution exposure on the glial cell line in the expression patterns of miR-320a and let-7e as two upstream factors.
Methods: Human glial cell line was prepared from the Pasteur Institute of Iran and cultured in a dulbecco’s modified eagle medium (DMEM) with 10% fetal bovine serum (FBS). The IC50 value of sialic acid was obtained by colorimetric assay for assessing cell metabolic activity 3-(4,5-Dimethylthiazol-2-yl (MTT), and the glial cell line was treated with sialic acid in 300, 500, 1000 µg/mL for 24 h to investigate the effect of the sialic acid ligand on the expression pattern of the miR-320a and let-7e. Total RNA was isolated from approximately 10×106 glial cells and was used from each sample for complementary dna (cDNA) synthesis. For quantitative analysis of miR-320a and let-7e, we used real-time polymerase chain reaction (PCR), and for statistical analysis, the SPSS v. 21 software was applied.
Results: Analyzing the real-time data revealed that the expression of miR-320a and let-7e was significantly increased (P<0.0001) in 300, 500, and 1000 µg/mL treated glial cells by sialic acid compared to the control group.
Conclusion: A possible linkage of sialic acid on miR-320a and let-7e regulation was observed in the glial cell line as proinflammatory factors in the inflammation pathway.
Kiana Karimifar, Hiva Alipanah, Ava Solatani Hekmat, Mohammad Reza Bigdeli,
Volume 13, Issue 3 (5-2022)
Abstract
Introduction: The death of neurons and cerebral edema are the main consequences of stroke. However, inflammatory processes play key roles in aggravating cerebral damage following a stroke. This study aimed to investigate the effects of Viola odorata extract (VOE) on the infarct volume (IV), neurologic deficits (ND), and the expression of NF-κB and VCAM-1 in the Middle Cerebral Artery Occlusion (MCAO) model.
Methods: The animals were randomly separated into 6 groups: (1) control group, (2) vehicle-treated group, (3) MCAO group, (4) VOE25 group, (5) VOE50 group, and (6) VOE75 group (n= 12). VOE (25, 50, and 75 mg/kg) and distilled water were administered daily for 30 days. Two hours after the last gavage, the rats were exposed to MCAO for 60 minutes. Twenty-four hours later, IV, ND, and NF-κB/VCAM-1 expressions were evaluated.
Results: Viola odorata extract exhibited excellent neuroprotective effects by reducing IV (mainly in the core and subcortex areas), and induced downregulation of NF-κB and VCAM-1 expression.
Conclusion: Viola odorata could also activate intracellular pathways, reducing the expression of NF-κB and VCAM-1. It is useful for developing a novel medical herb for treating cerebral ischemia.
Ebrahim Savareh, Nahid Davoodian, Ronak Mousaviyan, Maryam Ghasemi-Kasman, Ali Atashabparvar, Ebrahim Eftekhar,
Volume 13, Issue 3 (5-2022)
Abstract
Introduction: Evidence suggests that gestational exposure to Lipopolysaccharide (LPS) results in fetal zinc deficiency and eventually neurodevelopmental abnormalities. In this study, we utilized a rat model of Maternal Immune Activation (MIA) to investigate the possible neuroprotective effects of zinc supplementation during pregnancy on hippocampal astrocytes activation as well as inflammatory cytokines expression in adult offspring.
Methods: Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline on Gestational Days (GD) 15 and 16, and orally gavaged with zinc sulfate (30 mg/kg) during pregnancy. Astrocyte density and histological assessment were evaluated in the hippocampus of adult offspring on Postnatal Days (PND) 60 to 62. Also, the mRNA levels of IL-6, TNF-α, IL-1β, NF-κB, and GFAP were measured using qPCR analysis.
Results: Prenatal exposure to LPS resulted in upregulated expression levels of IL-6, TNF-α, NF-κB, and GFAP in the hippocampus of adult pups. Moreover, the offspring from the LPS group showed an increased astrocyte density in the CA1 region with no histological alterations in CA1 and CA3 areas. However, maternal zinc supplementation ameliorated the LPS-induced inflammatory alterations.
Conclusion: This study supports the premise that zinc supplementation during pregnancy might be an early treatment option to inhibit hippocampal inflammation induced by the maternal immune response to infectious agents.
Khojasteh Rahimi Jaberi, Manouchehr Safari, Vahid Semnani, Hamid Reza Sameni, Sam Zarbakhsh, Laya Ghahari,
Volume 13, Issue 5 (9-2022)
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.
Ardeshir Moayeri, Rafieh Alizadeh, Hatef Ghasemi Hamidabadi, Maryam Nazm Bojnordi, Ali Niapour, Azim Hedayatpour, Marzieh Darvishi, Fatemeh Heidari, Maryam Soleimani, Leila Elyasi,
Volume 13, Issue 5 (9-2022)
Abstract
Introduction: The induction of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) toward dopaminergic neurons is a major challenge in tissue engineering and experimental and clinical treatments of various neurodegenerative diseases, including Parkinson disease. This study aims to differentiate HUC-MSCs into dopaminergic neuron-like cells.
Methods: Following the isolation and characterization of HUC-MSCs, they were transferred to Matrigel-coated plates and incubated with a cocktail of dopaminergic neuronal differentiation factors. The capacity of differentiation into dopaminergic neuron-like cells in 2-dimensional culture and on Matrigel was assessed by real-time polymerase chain reaction, immunocytochemistry, and high-performance liquid chromatography.
Results: Our results showed that dopaminergic neuronal markers’ transcript and protein levels were significantly increased on the Matrigel differentiated cells compared to 2D culture plates.
Conclusion: Overall, the results of this study suggest that HUC-MSCs can successfully differentiate toward dopaminergic neuron-like cells on Matrigel, having great potential for the treatment of dopaminergic neuron-related diseases.
Marjaneh Motaghed, Davood Sanooghi, Zohreh Bagher, Faezeh Faghihi, Abolfazl Lotfi, Ali Shahbazi, Mohammad Taghi Jogataei,
Volume 13, Issue 5 (9-2022)
Abstract
Introduction: Maintenance of neurogenesis depends on the function of some histone-modifying enzymes; including Enhancer of zeste homolog 2 (EZH2) and histone acetyltransferases (P300). The mechanism of epigenetic regulation and gene expression underlying the transition of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into MNs has not been fully clarified.
Methods: Two morphogens; sonic hedgehog (Shh: 100 ng/mL) and retinoic acid (RA: 0.01 mM) were involved in the specification of hUCB-MSCs into MNs after MSC characterization using Flow cytometry. Real time-quantitative PCR and immunocytochemistry were performed to find the expression of the genes at the level of mRNA and protein.
Results: The expression of MN-related markers was confirmed at the level of mRNA and protein by induction of differentiation. The results were confirmed by immunocytochemistry and showed those mean cell percentages of 55.33%±15.885% and 49.67%±13.796% could express Islet-1 and ChAT, respectively. The gene expression level of Islet-1 and ChAT was significantly increased in the first and second week of exposure, respectively. After two weeks, the expression level of P300 and EZH-2 genes increased remarkably. No significant expression of Mnx-1 was detected when compared to the control sample.
Conclusion: MN-related markers, Islet-1 and ChAT, were detected in differentiated cells of hUCB-MSCs, supporting the potency of cord blood cells in the regeneration of MN-related disorders. Assessing these epigenetic regulatory genes at the protein level can be suggested to confirm their functional epigenetic modifying effects during motor neuron differentiation.
Hamid Mirhosseini, Masoud Kargar, Michael Nitsche, Mohammad Ali Sheikhi Abarghouei, Mohammad Ali Nazari, Ghasem Dastjerdi,
Volume 13, Issue 6 (11-2022)
Abstract
Introduction: The persistence of post-detoxification problems in drug addiction is one of the disadvantages of the ultra-rapid opioid detoxification (UROD) method. Transcranial direct current stimulation (tDCS) has been introduced in experimental addiction treatment for some years. Results of pilot studies suggest that it might be a promising method for addiction treatment. This study explores the adjunctive application of tDCS during treating opiate addiction with the UROD approach.
Methods: This double-blind, sham-controlled clinical trial was carried out on patients with substance abuse admitted to the Bahman Clinic of Yazd City in Iran (from March to September 2014). Forty participants were randomly allocated to treatment and control groups. Two sessions of tDCS (real or sham) over dorsolateral prefrontal cortices (DLPFC) were applied, accompanied by UROD. Withdrawal symptoms and craving were assessed by the drug desire questionnaire and objective opiate withdrawal scale before UROD and for the 24-hour interval after.
Results: Transcranial direct current stimulation optimized the opiate addiction treatment through craving and withdrawal syndrome alleviation.
Conclusion: The study results indicate that prefrontal tDCS may promote the efficacy of the UROD method in opioid addiction.
Gabriel Olaiya Omotoso, Ridwan Adeniyi Olanrewaju, Nathaniel O. Amedu, Rhoda Mama Kolo, Ismail Temitayo Gbadamosi,
Volume 13, Issue 6 (11-2022)
Abstract
Introduction: The neurotoxic effects of aluminum exposure during the critical period of neurodevelopment have been well documented. This study investigated the known protective effects of calcium supplementation on the cerebellum of juvenile Wistar rats following aluminum-induced neurotoxicity during lactation.
Methods: Four groups of juvenile rats were exposed via lactation to distilled water (control group), aluminum (40 mg/kg/d), calcium supplement (50 mg/kg/d), and a combination of both aluminum and calcium from postnatal day 4 to day 28. The cerebella of the animals were excised to access the levels of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]), lipid peroxidation (malondialdehyde), histomorphological alterations (hematoxylin and eosin staining), Nissl profile (cresyl fast violet staining), and glial activation (glial fibrillary acidic protein immunohistochemistry).
Results: Lactational aluminum significantly decreased the activities of superoxide dismutase and glutathione peroxidase while exacerbating lipid peroxidation and reactive astrocyte in cerebellar lysates. Lactational calcium supplementation normalized the activities of SOD and GPx, thereby preventing excessive lipid peroxidation and glial activation. Despite no apparent changes in the general histology of the cerebellum, aluminum-induced chromatolysis changes in the Purkinje cell layer, which was counteracted by the antioxidant propensities of calcium supplementation.
Conclusion: These findings support that calcium supplementation significantly protects the cerebellum against aluminum-induced oxidative stress, chromatolysis, and neuroinflammation.
