Basic and Clinical Neuroscience最新文献

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.

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.

Introduction: The functions of the endoplasmic reticulum (ER) are important, particularly in the proteins' synthesis, folding, modification, and transport. Based on traditional medicine and our previous studies on Zanthoxylum alatum in lipopolysaccharide-induced depressive behavior and scopolamine-induced impaired memory, the present study explored the role of hydroalcoholic extract of Z. alatum (ZAHA) seeds in reducing the ER stress in mice.

Methods: The mice were restrained for 28 days in polystyrene tubes. ZAHA (100 and 200 mg/kg, PO) and imipramine (10 mg/kg, IP) were administered daily, 45 min before restraint from day 22 to 28. The mice were assessed by the forced swim test. Also, the antioxidant enzyme levels of Superoxide Dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation (LPO) were measured in the hippocampus of mice. The expression of 78 kDa glucose-regulated protein (GRP78), 94 kDa Glucose-Regulated Protein (GRP94), and C/EBPhomologous protein (CHOP) genes was assessed by real-time PCR to explore the molecular mechanism.

Results: ZAHA (100 and 200 mg/kg, PO, and imipramine, IP) counteracted the stress by significantly reducing the immobility time in the force swimming test, receding oxidative stress and lipid peroxidation. The antioxidant enzyme (SOD and GSH) levels were elevated in the restraint stress group. Down-regulation of genes (GRP78, GRP94, and CHOP) compared to the chronic restraint stress group indicated stress modulating properties of the seeds in ER stress. Hesperidin, magnoflorine, melicopine, and sesamin, isolated from the active extract, were hypothesized to exert the activity.

Conclusion: It can be concluded that Z. alatum reverted chronic restraint stress through its antioxidant properties and down-regulation of genes involved in ER stress.

Introduction: The present systematic review and meta-analysis aims to conduct a comprehensive and complete search of electronic resources to investigate the role of administrating Chondroitinase ABC (ChABC) in improving complications following Spinal Cord Injuries (SCI).

Methods: MEDLINE, Embase, Scopus, and Web of Sciences databases were searched until the end of 2019. Two independent reviewers assessed the studies conducted on rats and mice and summarized the data. Using the STATA 14.0 software, the findings were reported as pooled standardized mean differences (SMD) with 95% confidence intervals (CI).

Results: A total of 34 preclinical studies were included. ChABC administration improves locomotion recovery after SCI (SMD=0.90; 95% CI: 0.61 to 1.20; P<0.001). The subgroup analysis showed that the differences in the SCI model (P=0.732), the severity of the injury (P=0.821), the number of ChABC administrations (P=0.092), the blinding status (P=0.294), the use of different locomotor score (P=0.567), and the follow-up duration (P=0.750) have no effect on the efficacy of ChABC treatment.

Conclusion: The findings of the present study showed that prescribing ChABC has a moderate effect in improving locomotion after SCI in mice and rats. However, this moderate effect introduces ChABC as adjuvant therapy and not as primary therapy.

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.

Introduction: Alzheimer disease (AD) is the most common form of dementia worldwide. The modalities to diagnose AD are generally expensive and limited. Both the central nervous system (CNS) and the retina are derived from the cranial neural crest; therefore, changes in retinal layers may reflect changes in the CNS tissue. Optical coherence tomography (OCT) machine can show delicate retinal layers and is widely used for retinal disorders. This study aims to find a new biomarker to help clinicians diagnose AD via retinal OCT examination.

Methods: After considering the inclusion and exclusion criteria, 25 patients with mild and moderate AD and 25 healthy subjects were enrolled in the study. OCT was done for all eyes. The central macular thickness (CMT) and the ganglion cell complex (GCC) thickness were calculated. The groups were compared using the SPSS software, v. 22.

Results: Both GCC thickness and CMT were significantly decreased in patients with AD when compared to healthy age- and sex-matched individuals.

Conclusion: Retinal changes, specifically CMT and GCC thickness, may reflect the AD process in the brain. OCT can be considered a non-invasive and inexpensive method to help diagnose AD.

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that is associated with an increased risk of infertility. This study aims to evaluate the neurobehavioral and neurochemical changes along with the associated changes in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) of the dehydroepiandrosterone (DHEA)-induced PCOS model rats.

Methods: A total of 12 female juvenile Wistar rats (30 to 50 g) about 22 to 44 days old were divided into 2 groups. The control group received sesame oil while the PCOS group received sesame oil plus DHEA. All treatment was done via daily subcutaneous injection for 21 days.

Results: Subcutaneous DHEA-induced PCOS significantly depleted the line crossing and rearing frequency in the open field, along with the percentage of the time in the white box, line crossing, rearing, and peeping frequency in the black and white box, and the percentage of alternation in the Y-maze. PCOS significantly increased the immobility time, freezing period, and the percentage of time in the dark area in the forced swim test, open field test, and black and white box, respectively. The level of luteinizing hormone, follicle-stimulating hormone, malondialdehyde (MDA), reactive oxygen species (ROS), and interleukin-6 (IL-6) increased significantly, while norepinephrine depleted significantly with an obvious decrease in the brain-derived neurotrophic factor level in the PCOS model rats. PCOS rats exhibited cystic follicles in the ovaries and necrotic or degenerative like features in the hippocampal pyramidal cells.

Conclusion: DHEA-induced PCOS results in anxiety and depressive behavior with structural alteration in rats, possibly through the elevation of MDA, ROS, and IL-6 levels, which also attributes to impaired emotional and executive functions in the mPFC and ACC.

Introduction: The human brain is a complex system consisting of connected nerve cells that adapt to and learn from the environment by changing its regional activities. The synchrony between these regional activities is called functional network changes during life and results in the learning of new skills. Time perception and interval discrimination are among the most necessary skills for the human being to perceive motions, coordinate motor functions, speak, and perform many cognitive functions. Despite its importance, the underlying mechanism of changes in brain functional connectivity patterns during learning time intervals still need to be well understood.

Methods: This study aimed to show how electroencephalography (EEG) functional connectivity changes are associated with learning temporal intervals. In this regard, 12 healthy volunteers were trained with an auditory time-interval discrimination task over six days while their brain activities were recorded via EEG signals during the first and the last sessions. Then, changes in regional phase synchronization were calculated using the weighted/phase lag index (WPLI) approach, the most effective EEG functional connections at the temporal and prefrontal regions, and in the theta and beta bands frequency. In addition, the WPLI reported more accurate values.

Results: The results showed that learning interval discrimination significantly changed functional connectivity in the prefrontal and temporal regions.

Conclusion: These findings could shed light on a better understanding of the brain mechanism involved in time perception.

Highlights: Accuracy of auditory interval discrimination improved by a six-day learning process.Most established connections were formed in the temporal, occipital and middle regions of brain.Creation of new significant connection was observed at the theta and gamma frequency bands.New neural networks are constructed between regions of the brain during interval learning.

Plain language summary: The time perception is a vital challenge that human beings face in various aspects of their lives. Researchers have always been challenged in how to calculate it and understand its mechanism for each individual. In the present study, which is based on the temporal perception, by comparing the timing of auditory stimuli, we seek to show the functional relationships of neural network formation related to learning temporal perception. Our aim was to understand how the hidden information of auditory stimuli (time intervals) is encoded in the content of the brain signals.

Introduction: Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system. The current research aimed to evaluate the impact of berberine hydrochloride on improving cognitive function and neuroprotective effects in rats addicted to MA.

Methods: In this study, 27 male Wistar rats were randomly assigned to three groups, including control, MA addiction, and MA addiction with berberine hydrochloride (100 mg/kg/d) orally during the three weeks of withdrawal. Two groups received self-administered inhaled MA for two weeks (up to 10 mg/kg). Following the experimental procedures, a Morris water maze (MWM) and shuttle box were used to assess memory, and hippocampal sections from the animals were examined for caspase-3, Ki-67, and glial fibrillary acidic protein (GFAP) expression.

Results: The obtained results from the Morris water maze (MWM) showed that berberine hydrochloride decreases (P<0.01) the distance moved and the time spent to reach the hidden platform in the four-day learning trails phase and significant differences were observed in the distance moved, spent time, and frequency of motion in target quadrant on probe test day between groups. Berberine hydrochloride also reduced the latency of animals entering the dark chamber in the treated group compared to the control group (P<0.05). A significant decrease in activation of caspases-3, higher percentages of Ki-67 expression, and an increase in glial fibrillary acidic protein (GFAP) expression of cells was observed in the addicted group compared to the berberine-treated and control groups (P<0.05).

Conclusion: Administration of berberine hydrochloride for 3 weeks improves cognitive function in MA addiction and it has potential neuroprotective efficacy.

Highlights: Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system.The berberine hydrochloride effects on improving cognitive function and neuroprotective.No approved pharmacotherapy, as well as confirmed medication, is available to treat MA abuse.

Plain language summary: Methamphetamine (MA) is known as a strong addictive stimulant with high addiction and no approved pharmaco-therapy, as well as confirmed medication, is available to treat MA abuse. The study on the long-term effect of MA exposure on cognitive function during an object recognition memory test showed cognitive dysfunction after MA exposure. Berberine can reduce induced amnesia, which can be due to the increased peripheral and central cholinergic neuronal system functions, in addition, the most important mechanism in the protective effect of berberine against amnesia is the inhabitation of inflammation; however, the berberine impact on cells should be more investigated.