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Huntington's disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cells in the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities including pharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeutic potential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group, a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuously over a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection within an experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and open field assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level in the treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatory and fibrotic factors in the HD model.
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Epilepsy is a common neurological disorder that significantly affects the quality of life of patients. In this study, we aim to evaluate the effectiveness of dental pulp stem cell (DPSC) transplantation in decreasing inflammation and cell death in brain cells, thus reducing seizure damage. We induced seizures in rats using intraperitoneal injections of pentylenetetrazole (PTZ). In the PTZ + DPSC group, we conducted bilateral hippocampal transplantation of DPSCs in PTZ-lesioned rat models. After 1 month, we performed post-graft analysis and measured some behavioral factors, such as working memory and long-term memory, using a T-maze test and passive avoidance test, respectively. We investigated the immunohistopathology and distribution of astrocyte cells through light microscopy and Sholl analysis. Additionally, we employed the Voronoi tessellation method to estimate the spatial distribution of the cells in the hippocampus. Compared to the control group, we observed a reduction in astrogliosis, astrocyte process length, the number of branches, and intersections distal to the soma in the hippocampus of the PTZ + DPSC group. Further analysis indicated that the grafted DPSCs decreased the expression of caspase-3 in the hippocampus of rats with induced seizures. Moreover, the DPSCs transplant protected hippocampal pyramidal neurons against PTZ toxicity and improved the spatial distribution of the hippocampal neurons. Our findings suggest that DPSCs transplant can be an effective modifier of astrocyte reactivation and inflammatory responses.
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Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.
Asunto(s)
Modelos Animales de Enfermedad , Vesículas Extracelulares , Sangre Fetal , Gliosis , Enfermedad de Huntington , Fármacos Neuroprotectores , Animales , Vesículas Extracelulares/metabolismo , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Ratas , Humanos , Gliosis/patología , Fármacos Neuroprotectores/farmacología , Masculino , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Ratas Wistar , Nitrocompuestos , PropionatosRESUMEN
Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Ratas , Animales , Dimesilato de Lisdexanfetamina/uso terapéutico , Dextroanfetamina , Resultado del Tratamiento , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Amnesia/inducido químicamente , Estimulantes del Sistema Nervioso Central/farmacología , Método Doble CiegoRESUMEN
Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.
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Apoptosis , Dimesilato de Lisdexanfetamina , Motilidad Espermática , Espermatozoides , Testículo , Animales , Masculino , Apoptosis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/patología , Dimesilato de Lisdexanfetamina/toxicidad , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Motilidad Espermática/efectos de los fármacos , Ratas Sprague-Dawley , Inflamación/inducido químicamente , Inflamación/patología , Ratas , Testosterona , Fragmentación del ADN/efectos de los fármacos , Caspasa 3/metabolismoRESUMEN
3-acetylpyridine (3-AP) is a neurotoxin that is known to mainly affect the inferior olivary nucleus (ION) in the brain stem. Although several studies have explored the effect of this neurotoxin, still further investigation is required to understand the impact of this toxin on different parts of the brain. In this research, two groups of rats were studied, the 3-AP-treated and the control groups. Behavioral, stereological, and immunohistochemical analyses were performed. The locomotor activity of the 3-AP-treated rats decreased whereas their anxiety levels were higher than in normal controls. Also, memory performance was impaired in animals in the 3-AP group. Microscopic observations showed a decline in the numerical density of neurons in the hippocampus and striatum along with gliosis. Although this toxin is used to affect the ION, it exerts a neurotoxic effect on different brain regions.
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Encéfalo , Neurotoxinas , Ratas , Masculino , Animales , Neurotoxinas/toxicidad , Hipocampo , Piridinas/toxicidadRESUMEN
This study evaluates whether elderberry (EB) effectively decreases the inflammation and oxidative stress in the brain cells to reduce Aß toxicity. In the Aß + EB group, EB powder was added to rats' routine diet for eight consecutive weeks. Then, spatial memory, working memory, and long-term memory, were measured using the Morris water maze, T-maze, and passive avoidance test. Also, in this investigation immunohistopathology, distribution of hippocampal cells, and gene expression was carried out. Voronoi tessellation method was used to estimate the spatial distribution of the cells in the hippocampus. In addition to improving the memory functions of rats with Aß toxicity, a reduction in astrogliosis and astrocytes process length and the number of branches and intersections distal to the soma was observed in their hippocampus compared to the control group. Further analysis indicated that the EB diet decreased the caspase-3 expression in the hippocampus of rats with Aß toxicity. Also, EB protected hippocampal pyramidal neurons against Aß toxicity and improved the spatial distribution of the hippocampal neurons. Moreover, EB decreased the expression of inflammatory and apoptotic genes. Overall, our study suggest that EB can be considered a potent modifier of astrocytes' reactivation and inflammatory responses.
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The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future.
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Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.
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Epilepsia , Células de Sertoli , Masculino , Ratas , Humanos , Animales , Células de Sertoli/patología , Calidad de Vida , Convulsiones/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Hipocampo/metabolismo , Muerte Celular , Amnesia/metabolismoRESUMEN
BACKGROUND: The choroid plexus (CP) is the principal source of cerebrospinal fluid (CSF). It can produce and release a wide range of materials, including growth and neurotrophic factors which have a crucial role in the maintenance and proper functioning of the brain. Tramadol is a synthetic analog of codeine, mainly prescribed to alleviate mild to moderate pains. Nevertheless, it causes several side effects, such as emotional instability and anxiety. METHODS: In this study, we focused on alterations in the expression of inflammatory and apoptotic genes in the CP under chronic tramadol exposure. Herein, rats were treated daily with tramadol at 50 mg/kg doses for three weeks. CSF samples were collected, with superoxide dismutase (SOD) and glutathione (GSH) measured in the CSF. RESULTS: We found that tramadol reduced the SOD and GSH levels in the CSF. Furthermore, the stereological analysis revealed a significant increase in the CP volume, epithelial cells, and capillary number upon tramadol administration. Tramadol elevated the number of blob mitochondria in CP. Also, we observed the upregulation of inflammatory and apoptosis genes following tramadol administration in the CP. CONCLUSIONS: Our findings indicate that tramadol induces neurotoxicity in the CP via apoptosis, inflammation, and oxidative stress.
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Tramadol , Ratas , Animales , Tramadol/farmacología , Plexo Coroideo/metabolismo , Estrés Oxidativo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Glutatión/metabolismo , Apoptosis , Superóxido Dismutasa/metabolismoRESUMEN
Irritable bowel syndrome (IBS) is related to a problem in the gut-brain axis. This experimental research aimed to shed light on the potential therapeutic application of elderberry (EB), which can work on the axis and get better the IBS symptoms. There were three groups (36 Sprague-Dawley rats) in this experiment, including control, IBS, and IBS with EB diet (IBS + EB). Making use of intracolonic instillation of 1 ml of 4% acetic acid for 30 s, IBS was induced. 7 days later, the EB extract (2%) was added to the diets of all animals for 8 weeks. Some histological, behavioral, and stereological techniques were used to detect the effects of EB on the gut and brain tissues. The findings showed that the EB diet improved locomotion and decreased anxiety-like behavior in the rat models of IBS. Moreover, the diet dropped the expression of TNF-α and increased mucosal layer thickness and the number of goblet and mast cells in colon tissue samples. In the hippocampal samples, administration of EB prevented astrogliosis and astrocyte reactivity. Although hippocampal and cortical neurons decreased markedly in the IBS group, EB prevented the drop in the number of neurons. Although lots of research is needed to elucidate the effectiveness of EB in IBS and its exact molecular mechanism, the result of this study showed that EB as an antioxidant and immune-modulatory agent could be a promising research target to prevent the impairment in the gut-brain axis, and could ameliorative classic IBS symptoms.
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Disfunción Cognitiva , Síndrome del Colon Irritable , Sambucus , Ratas , Animales , Síndrome del Colon Irritable/tratamiento farmacológico , Síndrome del Colon Irritable/psicología , Eje Cerebro-Intestino , Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Disfunción Cognitiva/tratamiento farmacológico , DietaRESUMEN
Reports have emerged on the sudden opioid-induced auditory hearing loss, and the underlying pathology is not fully understood. The present study aimed to determine the mechanism of action of these drugs in the inner ear. For this purpose, 20 rats were treated with 50 mg/kg tramadol daily for three weeks. Next, the stereological and immunohistochemical alteration of the inner hair cells under chronic exposure to tramadol was evaluated. The results revealed that tramadol induced hair cell degeneration and decreased bipolar neurons of the spiral ganglion and the thickness of stria vascularis. Moreover, immunohistochemistry showed that tramadol caused apoptosis in inner hair cells and bipolar neurons. These findings indicate that tramadol induces apoptosis in auditory hair cells, suggesting that tramadol may cause hearing loss and ototoxicity.
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Pérdida Auditiva , Tramadol , Ratas , Masculino , Animales , Tramadol/toxicidad , Células Ciliadas Auditivas , Estría Vascular/patología , Apoptosis , Pérdida Auditiva/patologíaRESUMEN
BACKGROUND: Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. This study aims to investigate the therapeutic effects of melittin (MEL) on a 3-acetylpyridine-induced (3-AP) cerebellar ataxia (CA) rat model. METHODS: Initially, CA rat models were generated by 3-AP administration followed by the subcutaneous injection of MEL. The open-field test was used for the evaluation of locomotion and anxiety. Immunohistochemistry was also conducted for the autophagy markers of LC3 and Beclin1. In the next step, the morphology of the astrocyte, the cell responsible for maintaining homeostasis in the CNS, was evaluated by the Sholl analysis. RESULTS: The findings suggested that the administration of MEL in a 3-AP model of ataxia improved locomotion and anxiety (P < 0.001), decreased the expression of LC3 (P < 0.01) and Beclin1 (P < 0.05), increased astrocyte complexity (P < 0.05) and reduced astrocyte cell soma size (P < 0.001). CONCLUSIONS: Overall, the findings imply that the MEL attenuates the 3-AP-induced autophagy, causes cell death and improves motor function. As such, it could be used as a therapeutic procedure for CA due to its neuroprotective effects.
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Ataxia Cerebelosa , Meliteno , Animales , Ratas , Ataxia/metabolismo , Autofagia , Beclina-1/metabolismo , Muerte Celular , Ataxia Cerebelosa/inducido químicamente , Ataxia Cerebelosa/tratamiento farmacológico , Ataxia Cerebelosa/metabolismo , Gliosis/metabolismo , Meliteno/farmacología , Células de Purkinje , Ratas Sprague-DawleyRESUMEN
Methadone is a centrally-acting synthetic opioid analgesic widely used in methadone maintenance therapy (MMT) programs throughout the world. Given its neurotoxic effects, particularly on the hippocampus, this study aims to address the behavioral and histological alterations in the hippocampus associated with methadone administration. To do so, twenty-four adult male albino rats were randomized into two groups, methadone treatment and control. Methadone was administered subcutaneously (2.5-10 mg/kg) once a day for two consecutive weeks. A comparison was drawn with behavioral and structural changes recorded in the control group. The results showed that methadone administration interrupted spatial learning and memory function. Accordingly, treating rats with methadone not only induced cell death but also prompted the actuation of microgliosis, astrogliosis, and apoptotic biomarkers. Furthermore, the results demonstrated that treating rats with methadone decreased the complexity of astrocyte processes and the complexity of microglia processes. These findings suggest that methadone altered the special distribution of neurons. Also, a substantial increase was observed in the expression of TNF-α due to methadone. According to the findings, methadone administration exerts a neurodegenerative effect on the hippocampus via dysregulation of microgliosis, astrogliosis, apoptosis, and neuro-inflammation.
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Gliosis , Metadona , Masculino , Analgésicos Opioides/toxicidad , Gliosis/patología , Hipocampo/metabolismo , Metadona/toxicidad , Metadona/metabolismo , Microglía , Enfermedades Neuroinflamatorias , Animales , RatasRESUMEN
Cell replacement therapy (CRT) is one of the most effective approaches used to alleviate symptoms of neurodegenerative syndromes such as cerebellar ataxia (CA). Human olfactory epithelium mesenchymal stem cells (OE-MSCs) have been recognized as a promising candidate for CRT, due to their distinctive features including immunomodulatory properties and ease of accessible compared to other types of MSCs. Hence, the main goal of our study was to explore the impacts of OE-MSCs transplantation on behavioral, structural, and histological deficiencies in a rat model of CA. After obtained an informed consent from volunteers, OE-MSCs were obtained from their nasal cavity. Then, OE-MSCs were characterized by the positive expression of CD73, CD90, and CD105 as MSCs as well as nestin and vimentin as primitive neuroectodermal stem cells markers. Then, the animals were randomized into three control, 3-acetylpyridine (3-AP) treated, and 3-AP + cell groups. In both experimental groups, the rats received intraperitoneal injection of 3-AP (75 mg/kg), followed by the implantation of OE-MSCs into the cerebellum of 3-AP + cell group. The impact of engrafted OE-MSCs on motor coordination and performance along with biochemical, immunohistochemical, and stereological changes in the cerebellum of the rat models of CA were investigated. According to our findings, the administration of 3-AP decreased the cerebellar GSH concentration. The injection of 3-AP also altered the morphological characteristics of the cerebellar Golgi cells. On the other hand, OE-MSCs transplantation improved motor coordination in CA. Besides, the implantation of OE-MSCs reduced caspase-3 expression and microglia proliferation in the cerebellum upon 3-AP administration. Finally, the transplant of OE-MSCs protected Purkinje cells against 3-AP toxicity. In sum, the present study revealed considerable advantages of OE-MSCs in managing CA animal model.
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Ataxia Cerebelosa , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Humanos , Ratas , Ataxia Cerebelosa/terapia , Células Madre Mesenquimatosas/metabolismo , Mucosa OlfatoriaRESUMEN
Over the past years, several studies have also reported the adverse effects of hyperthermia on normal testicular tissues in several species including mice, rats, and humans. These deleterious impacts include temporarily drop in relative weight of testis along with a temporary partial or complete infertility. Sambucus nigra, also known as elderberry or sweet elder, is a source of bioactive compounds that has drawn growing attention for its potential beneficial effects in preventing and treating several diseases. This experimental research divided 30 mice into the following three groups: (1) control, (2) hyperthermia, and (3) hyperthermia receiving elderberry diet for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, immunohistochemistry against TNF-α and caspase-3 and serum testosterone, FSH and LH levels. Our outputs indicated that elderberry diet could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid, and Leydig cells together with an increasing level of the serum testosterone compared to the scrotal hyperthermia induced mice. In addition, it was found that the expression of TNF-α and caspase-3 significantly decreased in the treatment groups by elderberry diet compared to the scrotal hyperthermia-induced mice. In conclusion, it could be concluded that elderberry diet may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice.
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Sambucus , Animales , Masculino , Ratones , Caspasa 3/metabolismo , Dieta , Sambucus/metabolismo , Semillas/metabolismo , Espermatogénesis , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cerebellar ataxia (CA) is a condition in which cerebellar dysfunction leads to movement disorders such as dysmetria, asynergy and dysdiadochokinesia. This study investigates the therapeutic effects of Melittin (MEL) on 3-acetylpyridine-induced (3-AP) cerebellar ataxia (CA) rat model. Initially, CA rat models were generated by 3-AP administration followed by the intraperitoneal injection of MEL. Then, motor performance and electromyography (EMG) activity were assessed. Afterwards, the pro-inflammatory cytokines were analyzed in the cerebellar tissue. Moreover, the anti-apoptotic role of MEL in CA and its relationship with the protection of Purkinje cells were explored. The findings showed that the administration of MEL in a 3-AP model of ataxia improved motor coordination (P < 0.001) and neuro-muscular activity (p < 0.05), prevented the cerebellar volume loss (P < 0.01), reduced the level of inflammatory cytokines (p < 0.05) and thwarted the degeneration of Purkinje cells against 3-AP toxicity (P < 0.001). Overall, the findings imply that the MEL attenuates the 3-AP-induced inflammatory response. As such, it could be used as a treatment option for CA due to its anti-inflammatory effects.
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Ataxia Cerebelosa , Células de Purkinje , Animales , Apoptosis , Ataxia Cerebelosa/inducido químicamente , Ataxia Cerebelosa/tratamiento farmacológico , Meliteno , Piridinas , RatasRESUMEN
This study aimed to examine the expression of the genes associated with different development stages of primordial germ cells (PGCs) in differentiating mouse embryonic stem cells (mESCs). The cells were cultured in three groups of control, 10-8 M of all-trans retinoic acid and the combination of 10-7 M of Progesterone and retinoic acid for 7, 12, 17, and 22 days. Immunofluorescent and Quantitative RT-PCR were used to evaluate the effect of progesterone on the differentiation of mESCs into primordial germ cells. RA-treated cells exhibited increased expression of Fragilis, Stella, Dazl, Stra8, Sycp3, and Gdf9 genes and decreased expression of Oct4, Mvh genes compared to the non-treated controls. Furthermore, RA in combination with progesterone (RA?P) led to increased expression of Oct4, Fragilis, Stella, Dazl, Sycp3, Gdf9 and decreased expression of Mvh, and Stra8 genes compared to the RA-treated scenario. Immunofluorescence detection of Stella and Mvh showed that the expression levels of the cells treated with RA+P are much higher than those of the other groups. Our project showed that under the influence of the induced factors, mESCs can spontaneously differentiate into germ cells. Also, the combination of RA+P can enhance and accelerate the differentiation of mESCs into germ cells.
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Células Madre Embrionarias de Ratones/efectos de los fármacos , Progesterona/farmacología , Tretinoina/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Células Germinativas , Ratones , Células Madre Embrionarias de Ratones/fisiologíaRESUMEN
Huntington's disease (HD) is an inherited neurodegenerative disorder which begins in the striatum and then spreads to other neural areas. Known as a progressive movement cognitive disorder, HD has no efficient therapy. Although the exact mechanism of HD is still unknown, several different etiological processes such as oxidative stress have been shown to play critical roles. Also, the current evidence indicates a strong correlation between immune activation and neural damage induced by neuroinflammatory and apoptotic agents in neurodegenerative disorders. Thus, natural products like Elderberry (EB) could be considered as a novel and potential therapeutic candidate for the treatment of this disease. In this study EB was added to the daily ration of ordinary rats for two months in order to ameliorate inflammatory and oxidative responses in rats injected with 3-nitropropionic acid (3-NP) in an experimental model of HD. Using Rotarod and electromyography setups, we showed that EB diet significantly recovered motor failure and muscle incoordination in 3-NP injected rats compared to the control group. Also, the molecular findings implied that EB diet led to a significant drop in 3-NP induced growth in caspase-3 and TNF-α concentration. The treatment also improved striatal antioxidative capacity by a significant reduction in ROS and a remarkable rise in GSH, which might be correlated with motor recovery in the tests. In sum, the findings demonstrate the advantages of EB treatment in the HD rat model with a score of beneficial anti-oxidative and anti-inflammatory effects.
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Enfermedad de Huntington/inducido químicamente , Enfermedad de Huntington/dietoterapia , Actividad Motora/fisiología , Nitrocompuestos/toxicidad , Estrés Oxidativo/fisiología , Propionatos/toxicidad , Sambucus , Animales , Muerte Celular/fisiología , Modelos Animales de Enfermedad , Estimulación Eléctrica/métodos , Electromiografía/métodos , Enfermedad de Huntington/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Stem cell-based therapy has recently offered a promising alternative for the remedy of neurodegenerative disorders like Huntington's disease (HD). Herein, we investigated the potential ameliorative effects of implantation of dental pulp stem cells (DPSCs) in 3-nitropropionic acid (3-NP) rat models of HD. In this regard, human DPSCs were isolated, culture-expanded and implanted in rats lesioned with 3-NP. Post-transplantation examinations revealed that DPSCs were able to survive and augment motor skills and muscle activity. Histological analysis showed DPSCs treatment hampered the shrinkage of the striatum along with the inhibition of gliosis and microgliosis in the striatum of 3-NP rat models. We also detected the downregulation of Caspase-3 and pro-inflammatory cytokines such as TNF and IL-1ß upon DPSCs grafting. Overall, these findings imply that the grafting of DPSCs could repair motor-skill impairment and induce neurogenesis, probably through the secretion of neurotrophic factors and the modulation of neuroinflammatory response in HD animal models.