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3.
Mol Neurobiol ; 59(12): 7278-7292, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36175823

RESUMO

Astrocytes display an active, dual, and controversial role in multiple sclerosis (MS), a chronic inflammatory demyelination disorder. However, mesenchymal stem cells (MSCs) can affect myelination in demyelinating disorders. This study aimed to investigate the effect of single and combination therapies of astrocyte ablation and MSC transplantation on remyelination in the cuprizone (CPZ) model of MS. C57BL/6 mice were fed 0.2% CPZ diet for 12 weeks. Astrocytes were ablated twice by L-a-aminoadipate (L-AAA) at the beginning of weeks 13 and 14 whereas MSCs were injected in the corpus callosum at the beginning of week 13. Motor coordination and balance were assessed through rotarod test whereas myelin content was evaluated by Luxol-fast blue (LFB) staining and transmission electron microscopy (TEM). Glial cells were assessed by immunofluorescence staining while mRNA expression was evaluated by quantitative real-time PCR. Combination treatment of ablation of astrocytes and MSC transplantation (CPZ + MSC + L-AAA) significantly decreased motor coordination deficits better than single treatments (CPZ + MSCs or CPZ + L-AAA), in comparison to CPZ mice. In addition, L-AAA and MSCs treatment significantly enhanced remyelination compared to CPZ group. Moreover, combination therapy caused a significant decrease in the number of GFAP+ and Iba-1+ cells, whereas oligodendrocytes were significantly increased in comparison to CPZ mice. Finally, MSC administration resulted in a significant upregulation of BDNF and NGF mRNA expression levels. Our data indicate that transient ablation of astrocytes along with MSCs treatment improve remyelination through enhancing oligodendrocytes and attenuating gliosis in a chronic demyelinating mouse model of MS.


Assuntos
Doenças Desmielinizantes , Transplante de Células-Tronco Mesenquimais , Esclerose Múltipla , Remielinização , Animais , Camundongos , Cuprizona/toxicidade , Astrócitos/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/terapia , Doenças Desmielinizantes/metabolismo , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Modelos Animais de Doenças , Esclerose Múltipla/terapia , Esclerose Múltipla/metabolismo , RNA Mensageiro/metabolismo
4.
J Assist Reprod Genet ; 39(8): 1815-1824, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35713751

RESUMO

Despite the beneficial effects of sperm cryopreservation, increased reactive oxygen species (ROS) production during this process can affect spermatozoon structure and function. Moreover, ROS production is associated with elevated DNA damage and alterations in DNA methylation. There is little information about the effects of cryopreservation on epigenetic modulation in sperm and the health of children born with frozen spermatozoa. Considering the potential consequences of cryopreservation in ART-conceived children, it is necessary to assure that cryopreservation does not modify sperm DNA methylation status. This review summarizes reports on epigenetic modifications of spermatozoa during cryopreservation and the probable effects of this process on offspring health. Contradictory results have reported the influence of sperm cryopreservation on DNA methylation in imprinted genes. Multiclinical studies with larger sample sizes under the same conditions of cryopreservation and DNA methylation analysis are needed to make any definitive conclusion about the effect of the cryopreservation process on sperm DNA methylation.


Assuntos
Preservação do Sêmen , Criança , Criopreservação/métodos , Metilação de DNA/genética , Humanos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Sêmen , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides , Espermatozoides/metabolismo
5.
Reprod Biol Endocrinol ; 19(1): 85, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108007

RESUMO

BACKGROUND: The importance of spermatogonial stem cells (SSCs) in spermatogenesis is crucial and intrinsic factors and extrinsic signals mediate fate decisions of SSCs. Among endogenous regulators, microRNAs (miRNAs) play critical role in spermatogenesis. However, the mechanisms which individual miRNAs regulate self- renewal and differentiation of SSCs are unknown. The aim of this study was to investigate effects of miRNA-30a-5p inhibitor on fate determinations of SSCs. METHODS: SSCs were isolated from testes of neonate mice (3-6 days old) and their purities were performed by flow cytometry with ID4 and Thy1 markers. Cultured cells were transfected with miRNA- 30a-5p inhibitor. Evaluation of the proliferation (GFRA1, PLZF and ID4) and differentiation (C-Kit & STRA8) markers of SSCs were accomplished by immunocytochemistry and western blot 48 h after transfection. RESULTS: Based on the results of flow cytometry with ID4 and Thy1 markers, percentage of purity of SSCs was about 84.3 and 97.4 % respectively. It was found that expression of differentiation markers after transfection was significantly higher in miRNA-30a- 5p inhibitor group compared to other groups. The results of proliferation markers evaluation also showed decrease of GFRA1, PLZF and ID4 protein in SSCs transfected with miRNA-30a-5p inhibitor compared to the other groups. CONCLUSIONS: It can be concluded that inhibition of miRNA-30a-5p by overexpression of differentiation markers promotes differentiation of Spermatogonial Stem Cells.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , MicroRNAs/fisiologia , Espermatogênese/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células-Tronco Germinativas Adultas/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Autorrenovação Celular , Citometria de Fluxo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Imuno-Histoquímica , Proteínas Inibidoras de Diferenciação/metabolismo , Masculino , Camundongos , MicroRNAs/antagonistas & inibidores , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Antígenos Thy-1/metabolismo
6.
Cell Mol Neurobiol ; 41(7): 1467-1481, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594382

RESUMO

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. The main causes of MS disease progression, demyelination, and tissue damage are oxidative stress and mitochondrial dysfunction. Hence, the latter are considered as important therapeutic targets. Recent studies have demonstrated that mesenchymal stem cells (MSCs) possess antioxidative properties and are able to target mitochondrial dysfunction. Therefore, we investigated the effect of transplanting Wharton's jelly-derived MSCs in a demyelination mouse model of MS in which mice were fed cuprizone (CPZ) for 12 weeks. CPZ is a copper chelator that impairs the activity of cytochrome oxidase, decreases oxidative phosphorylation, and produces degenerative changes in oligodendrocytes, leading to toxic demyelination similar to those found in MS patients. Results showed that MSCs caused a significant increase in the percentage of myelinated areas and in the number of myelinated fibers in the corpus callosum of the CPZ + MSC group, compared to the CPZ group, as assessed by Luxol fast blue staining and transmission electron microscopy. In addition, transplantation of MSCs significantly increased the number of oligodendrocytes while decreasing astrogliosis and microgliosis in the corpus callosum of the CPZ + MSC group, evaluated by immunofluorescence. Moreover, the mechanism by which MSCs exert these physiological effects was found to be through abolishing the effect of CPZ on oxidative stress markers and mitochondrial dysfunction. Indeed, malondialdehyde significantly decreased while glutathione and superoxide dismutase significantly increased in CPZ + MSC mice group, in comparison witth the CPZ group alone. Furthermore, cell therapy with MSC transplantation increased the expression levels of mitochondrial biogenesis transcripts PGC1α, NRF1, MFN2, and TFAM. In summary, these results demonstrate that MSCs may attenuate MS by promoting an antioxidant response, reducing oxidative stress, and improving mitochondrial homeostasis.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Animais , Cuprizona/farmacologia , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Esclerose Múltipla/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo
7.
J Med Case Rep ; 14(1): 232, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33250043

RESUMO

BACKGROUND: The azygos venous system in the posterior mediastinum has a complex developmental pattern. CASE PRESENTATION: During the dissection of this region, we encountered a variation in this system. In this case, we observed that the accessory hemiazygos and hemiazygos veins in the left side passed anterior to the aorta and drained to the azygos vein located on the left side of the vertebral column. Other structures were normal in this area. CONCLUSIONS: This variation is important in mediastinal surgery and radiographic interpretation.


Assuntos
Veia Ázigos , Veias , Veia Ázigos/diagnóstico por imagem , Cadáver , Dissecação , Humanos , Mediastino/diagnóstico por imagem , Mediastino/cirurgia
8.
Metab Brain Dis ; 35(7): 1211-1224, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32638202

RESUMO

Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary manipulation to reduce calorie intake which has been shown to improve neuroprotection and attenuate neurodegenerative disorders. Here, we evaluated the effect of 33% CR regimen for 4 weeks on the remyelination capacity of Cuprizone (CPZ) induced demyelination in a mouse model of MS. Results showed that CR induced a significant increase in motor coordination and balance performance in CPZ mice. Also, luxol fast blue (LFB) staining showed that CR regimen significantly improved the remyelination in the corpus callosum of CPZ + CR mice compared to the CPZ group. In addition, CR regimen significantly increased the transcript expression levels of BDNF, Sox2, and Sirt1 in the corpus callosum of CPZ mice, while decreasing the p53 levels. Moreover, CR regimen significantly decreased the apoptosis rate. Furthermore, astrogliosis (GFAP + astrocytes) and microgliosis (Iba-1 + microglia) were significantly decreased by CR regimen while oligodendrogenesis (Olig2+) and Sirt1 + cell expression were significantly increased in the corpus callosum of CPZ + CR mice compared to the CPZ group. In conclusion, CR regimen can promote remyelination potential in a CPZ-demyelinating mouse model of MS by increasing oligodendrocyte generation while decreasing their apoptosis.


Assuntos
Encéfalo/fisiopatologia , Restrição Calórica , Doenças Desmielinizantes/induzido quimicamente , Esclerose Múltipla/induzido quimicamente , Remielinização/fisiologia , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Cuprizona , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/fisiopatologia , Modelos Animais de Doenças , Camundongos , Microglia/metabolismo , Destreza Motora/fisiologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/fisiopatologia , Bainha de Mielina/metabolismo
9.
Biopreserv Biobank ; 18(4): 329-336, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32716639

RESUMO

Excessive production of reactive oxygen species (ROS) during semen cryopreservation can induce structural and functional changes in spermatozoa. It is well known that antioxidants can mitigate the effect of ROS. Moreover, the application of antioxidants in freezing media is an appropriate strategy for protecting spermatozoa against deleterious effects of ROS during the cryopreservation process. As an example, oregano is a medicinal plant with important activities, with antiseptic, antibacterial, antithrombotic, and antioxidant properties. This study aimed at evaluating the antioxidant effects of oregano extract on cryopreserved human spermatozoa. In the first phase, 13 semen samples with different concentrations of oregano extract (0.0, 50, 100, 150, 300, and 500 µg/mL) were cryopreserved to achieve an optimal dose of oregano extract. Then, motility, viability, and plasma membrane integrity were evaluated. In the second phase, 20 samples were cryopreserved in freezing media supplemented with or without the optimal concentration of oregano (100 µg/mL). After thawing, motility, the levels of ROS, lipid peroxidation, and translocation of phosphatidylserine (PS) were evaluated. The results showed that 100 µg/mL oregano extract significantly increased the total motility in frozen-thawed spermatozoa in comparison with the control group (28.2 ± 4.3 vs. 42.4 ± 1.6, p < 0.05). This concentration significantly decreased the percentage of 2',7'-dichlorofluorescein-positive cells (25.53 ± 1.2 vs. 21.48 ± 1.2) and the malondialdehyde level (4.25 ± 0.7 vs. 0.82 ± 0.4 µM) (p < 0.05). In the oregano group, the percentage of vital spermatozoa without PS externalization was significantly higher than that in the control group (25.88 ± 1.6 vs. 16.8 ± 1.9, p < 0.001), while the percentage of dead spermatozoa with PS externalization spermatozoa was significantly lower than that in the control group (51.65 ± 1.4 vs. 60.36 ± 1.9, p < 0.05). In general, the addition of oregano extract to sperm freezing extender has protective effects against oxidative stress and apoptosis.


Assuntos
Antioxidantes/farmacologia , Criopreservação/métodos , Origanum/química , Extratos Vegetais/farmacologia , Espermatozoides/fisiologia , Adulto , Antioxidantes/química , Relação Dose-Resposta a Droga , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Preservação do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Adulto Jovem
10.
J Mol Histol ; 50(3): 263-271, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31016544

RESUMO

Oxidative stress with mitochondrial defects has a central role in the development and deterioration of Multiple sclerosis (MS). According to new findings of the effects of metformin on mitochondrial function, has attracted a lot of attention. Furthermore, it is suggested that metformin exerts its beneficial influence through AMP-activated protein kinase (AMPK) pathway. In the current study, we investigated the possible protective effects of metformin on oxidative stress and mitochondrial function by activating the AMPK pathway in the cuprizone-induced demyelination. Mice were fed with cuprizone for 6 weeks. Animals simultaneously received metformin. After sacrificing animals, myelinations, and gliosis, changes in transcription factor and biochemical analysis were assessed. Transmission electron microscopy and luxol fast blue staining revealed that the myelinated axons within corpus callosum of cuprizone-induced demyelination animals increased after administration of metformin. Metformin also upregulated the expression of mitochondrial biogenesis genes. Furthermore, the biochemical analysis demonstrated that metformin ameliorated the oxidative stress induced by cuprizone. Immunohistochemistry analysis showed that astrogliosis and microgliosis were decreased after metformin administration while it enhanced the number of oligodendrocytes. Our data implicated that metformin exerts its therapeutic effects on MS by AMPK signaling improved mitochondrial homeostasis and protected oligodendrocytes.


Assuntos
Metformina/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Proteínas Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Cuprizona/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Hemostasia/efeitos dos fármacos , Hemostasia/genética , Humanos , Camundongos , Mitocôndrias/genética , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/patologia , Oligodendroglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
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