RESUMEN
This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Insuficiencia Cardíaca/prevención & control , Disfunción Ventricular Derecha/prevención & control , Animales , Antiinflamatorios no Esteroideos/metabolismo , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Electrocardiografía , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/inmunología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/patología , Masculino , Tamaño de los Órganos , Ratas , Ratas Sprague-Dawley , Análisis de Supervivencia , Disfunción Ventricular Derecha/etiologíaRESUMEN
The current coronavirus pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a serious global health crisis. It is a major concern for individuals living with chronic disorders such as Parkinson's disease (PD). Increasing evidence suggests an involvement of oxidative stress and contribution of NFκB in the development of both COVID-19 and PD. Although, it is early to identify if SARS-CoV-2 led infection enhances PD complications, it is likely that oxidative stress may exacerbate PD progression in COVID-19 affected individuals and/or vice versa. In the current study, we sought to investigate whether NFκB-associated inflammatory pathways following oxidative stress in SARS-CoV-2 and PD patients are correlated. Toward this goal, we have integrated bioinformatics analysis obtained from Basic Local Alignment Search Tool of Protein Database (BLASTP) search for similarities of SARS-CoV-2 proteins against human proteome, literature review, and laboratory data obtained in a human cell model of PD. A Parkinson's like state was created in 6-hydroxydopamine (6OHDA)-induced differentiated dopamine-containing neurons (dDCNs) obtained from an immortalized human neural progenitor cell line derived from the ventral mesencephalon region of the brain (ReNVM). The results indicated that SARS-CoV-2 infection and 6OHDA-induced toxicity triggered stimulation of caspases-2, -3 and -8 via the NFκB pathway resulting in the death of dDCNs. Furthermore, specific inhibitors for NFκB and studied caspases reduced the death of stressed dDCNs. The findings suggest that knowledge of the selective inhibition of caspases and NFκB activation may contribute to the development of potential therapeutic approaches for the treatment of COVID-19 and PD.
RESUMEN
Water soluble beta-carotene (WS-BC) is a carotenoid form that has been developed as a food colorant. WS-BC is known to contain 10% of all-trans beta-carotene (AT-BC). The aim of the present study was to investigate in vivo tissue uptake of AT-BC after the administration of WS-BC into rats. Seven-week-old male rats were administered 20 mg of WS-BC dissolved in saline by intravenous injection into the tail vein. At 0, 6, 24, 72, 120 and 168 hours (n = 7/time), blood was drawn and liver, lungs, adrenal glands, kidneys and testes were dissected. The levels of AT-BC in the plasma and dissected tissues were quantified with HPLC. After intravenous administration, AT-BC level in plasma first increased up to 6 h and returned to normal at 72 h. In the testes, the AT-BC level first increased up to 24 h and then did not decrease but was retained up to 168 h. In the other tissues, the level first increased up to 6 h and then decreased from 6 to 120 or 168 h but did not return to normal. The accumulation of WS-BC in testes but not in the other 5 tissues examined may suggest that AT-BC was excreted or metabolized in these tissues but not in testes. Although WS-BC is commonly used as a food colorant, its effects on body tissues are still not clarified. Results of the present study suggest that further investigations are required to elucidate effects of WS-BC on various body tissues.
Asunto(s)
Colorantes de Alimentos/farmacocinética , beta Caroteno/farmacocinética , Animales , Colorantes de Alimentos/análisis , Masculino , Ratas , Ratas Sprague-Dawley , Solubilidad , Testículo/química , Distribución Tisular , beta Caroteno/análisis , beta Caroteno/sangreRESUMEN
Macrophages/microglia are implicated in spinal cord injury but their precise role in the process is not clear. Our previous studies have reported that radial glia (RG) possess properties of neural stem cells and remerged after central nervous system (CNS) injury which may play an important role in neural repair and regeneration. In the present study, we examined the expression of ED1 (a specific marker for activated macrophages/microglia) and RG in a spinal cord injury (SCI) model and detected the activation at 1, 4, 8, and 12 weeks in both dorsal funiculus and ventral white matter after SCI. For both ED1-positive cells and RG cells, there was a gradual increase in density and in number from 1 to 4 weeks followed by down-regulation up to 12 weeks after injury. The morphologies of macrophages and radial glia were different. However, some ED1-positive cells were also stained by RG marker. These results suggest that macrophages may have some lineage to radial glial cells.
Asunto(s)
Macrófagos/metabolismo , Proteínas de la Membrana/metabolismo , Microglía/citología , Microglía/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Células Madre/metabolismo , Animales , Biomarcadores/metabolismo , Recuento de Células , Ectodisplasinas , Inmunohistoquímica , Macrófagos/citología , Masculino , Proteínas del Tejido Nervioso/metabolismo , Ratas , Traumatismos de la Médula Espinal/patología , Células Madre/citologíaRESUMEN
Amygdala kindling is regarded as a model of temporal lobe epilepsy in humans because of many points of similarity. In amygdala kindling, bilateralization of epileptic seizures follows from the accumulation of stimulation and commissural fibers may play a role in this process. However, new progenies of cells following amygdala kindling have not been reported and the precise nature of how bilateralization occurs is not clear. In the present study, we aim to clarify the emergence of radial glia during the progress of amygdala kindling in mouse brain. For this purpose, immunohistochemical staining for 3CB2, which is a specific marker of radial glia, was employed. Immunoreactivity for 3CB2 was observed in the forceps minor, radiation of trunk and forceps major regions at Clonus 3 and more strongly at Clonus 5. In the forceps major, the cingulate gyrus showed immunopositive staining at Clonus 3, but the corpus callosum and alveus hippocampi showed staining only at Clonus 5. In the fimbria hippocampus, the anterior commissure posterior showed staining at Clonus 5. However, the anterior commissure anterior was not stained at the stage progressed to Clonus 5. These findings indicate stage and region dependent expression of progenitor cells in commissural fibers and suggest that these changes may accompany the formation of new circuits in seizure progression during amygdala kindling.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Excitación Neurológica/fisiología , Fibras Nerviosas/fisiología , Neuroglía/fisiología , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Animales , Antígenos/metabolismo , Biomarcadores , Epilepsia del Lóbulo Temporal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Coloración y EtiquetadoRESUMEN
Macrophages and microglia are implicated in spinal cord injury, but their precise role is not clear. In the present study, activation of these cells was examined in a spinal cord injury model using 2 different antibodies against ED1 clone and ionized calcium binding adaptor molecule 1 (Iba1). Activation was observed at 1, 4, 8, and 12 weeks after contusion injury and was compared with sham operated controls. Our results indicate that activation could be observed in both the dorsal funiculus and the ventral white matter area in the spinal cord at 5 mm rostral to the epicenter of injury. For both cells, there was a gradual increase in activation from 1-4 weeks, followed by down-regulation for up to 12 weeks. As a result, we could stain macrophages by ED1 and microglia by Iba1. We concluded that macrophages may play a role in the phagocytosis of denatured dendrites after spinal cord injury, while microglia may have some cooperative functions, as they were found scattered near the macrophages.
Asunto(s)
Macrófagos/metabolismo , Microglía/metabolismo , Traumatismos de la Médula Espinal/patología , Médula Espinal , Animales , Proteínas de Unión al Calcio/metabolismo , Inmunohistoquímica , Macrófagos/citología , Masculino , Proteínas de Microfilamentos , Microglía/citología , Ratas , Ratas Sprague-Dawley , Médula Espinal/anatomía & histología , Médula Espinal/metabolismo , Médula Espinal/patología , Traumatismos de la Médula Espinal/metabolismoRESUMEN
To investigate the changes in the principal subunit of N-methyl-D-aspartate (NMDA) receptor 1 (NR1) following the transient ischemia and postischemic hypothermia, in situ hybridization was used in the gerbil hippocampus. One of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, Glutamate receptor 2 (GluR2) was also investigated to compare with NR1. Even at 1 day, NR1 and GluR2 mRNAs in the CA1 region were reduced following ischemia. Although postischemic hypothermia prevented almost all the neuronal cell death by ischemia and inhibited the reduction of NR1 and GluR2 mRNAs in the CA1 region after 7 days, the downregulation of NR1 mRNA in the CA2 region was observed even at 1 day. This change was specific for NR1 and not for GluR2. These results suggest that the changes in NR1 and GluR2 receptors at the mRNA level would occur in spite of postischemic hypothermia. The phenomenon in the CA2 region may play an important role to rescue neuronal cell death by ischemia.
Asunto(s)
Hipocampo/metabolismo , Hipotermia Inducida , Ataque Isquémico Transitorio/metabolismo , Células Piramidales/metabolismo , Receptores AMPA/genética , Receptores de N-Metil-D-Aspartato/genética , Animales , Muerte Celular/genética , Regulación hacia Abajo/genética , Gerbillinae , Hipocampo/patología , Hipocampo/fisiopatología , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/terapia , Masculino , Células Piramidales/patología , ARN Mensajero/metabolismo , Transmisión Sináptica/genéticaRESUMEN
Repeated focal electrical stimulation of the brain is known to produce epileptogenesis, and this phenomenon is recognized as kindling. It is also considered to be a model of temporal lobe epilepsy. In the present study, morphological changes in areas around third ventricle in rat brain were examined according to the progression of kindling stage. Very few Glial Fibrillary Acidic Protein (GFAP)-positive astrocytes were present in ependymal cell layer at C0 stage. However, there was a specific increase in GFAP-positive cells in ependymal cell layer at stage C3 as compared to stage C0. Furthermore, GFAP-positive cells showed migration to subependymal zone (SEZ). By stage C5, almost all GFAP-positive cells had migrated to SEZ. While the precise mechanism of this cell migration is not clear, the results suggest a relationship between progression of kindling stage and astrogliosis.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Gliosis/patología , Gliosis/fisiopatología , Excitación Neurológica , Tercer Ventrículo/fisiopatología , Amígdala del Cerebelo/efectos de la radiación , Animales , Encéfalo/metabolismo , Encéfalo/fisiopatología , Encéfalo/efectos de la radiación , Recuento de Células , Muerte Celular/fisiología , Modelos Animales de Enfermedad , Estimulación Eléctrica/métodos , Epéndimo/metabolismo , Epéndimo/fisiopatología , Epilepsia del Lóbulo Temporal/metabolismo , Proteína Ácida Fibrilar de la Glía , Gliosis/metabolismo , Inmunohistoquímica/métodos , Etiquetado Corte-Fin in Situ/métodos , Masculino , Neuroglía/metabolismo , Neuroglía/fisiología , Ratas , Ratas Sprague-Dawley , Tercer Ventrículo/citologíaRESUMEN
The classical view of the function of radial glia in brain development is a supporting function guiding radial neural migration. However, recent evidence indicates that they may play key roles in neurogenesis and gliogenesis, as ubiquitous precursors that generate neurons and glia. Although we previously reported the emergence of radial glia after spinal cord injury in adult rats, their precise function in this process is still unknown. In the present study, we examined emergence of radial glia in rat brain during progression of kindling, by performing immunohistochemical staining for vimentin which is a specific marker of radial glia. Vimentin immunoreactivity was found to be highest at clonus 3 and then decreased at clonus 5 in the hippocampal formation, regions around the third ventricle, caudate putamen and lateral habenular nucleus. Contrast, vimentin immunoreactivity consistently increased with progression of kindling in the cingulum and parietal cortex. These findings indicate dynamic changes in vimentin expression dependent on the kindling stage of seizure-prone state, and suggest that these changes play roles in formation of new circuits following kindling.
Asunto(s)
Química Encefálica/fisiología , Excitación Neurológica/fisiología , Neuroglía/metabolismo , Vimentina/biosíntesis , Animales , Biomarcadores , Hipocampo/metabolismo , Hipocampo/patología , Inmunohistoquímica , Masculino , Lóbulo Parietal/metabolismo , Células Piramidales/metabolismo , Ratas , Ratas Sprague-Dawley , Tercer Ventrículo/metabolismoRESUMEN
BACKGROUND: Nestin is a class VI intermediate filament protein, expressed during early embryonic development in mammals. Postnatally, nestin and its mRNA are down-regulated and gradually disappear. Recently, nestin expression has been detected in the adult nervous system, and it has been suggested that this protein may be related to neurogenesis, although, its role in the mechanism of neurogenesis is not known. METHODS: The present study examined the localization of nestin in CNS tissue of the amygdaloid kindled rat by light and electron microscopy. RESULTS: Kindled animals showed nestin expression mainly in the piriform cortex and the perirhinal cortex. By light microscopy, nestin was shown to be expressed in astrocytes, neurons, and endothelial cells. Electron microscopy demonstrated nestin expression in endothelial cells, astrocytic perivascular end feet, the rare pericyte, neurons and oligodendrocytes. CONCLUSION: We conclude that epilepsy causes widespread nestin expression in many cell types in the CNS, including non-neural cells.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Excitación Neurológica/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Giro Parahipocampal/metabolismo , Lóbulo Temporal/metabolismo , Amígdala del Cerebelo/citología , Animales , Astrocitos/metabolismo , Estimulación Eléctrica , Células Endoteliales/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , Masculino , Nestina , Giro Parahipocampal/citología , Ratas , Ratas Sprague-Dawley , Lóbulo Temporal/citología , Distribución TisularRESUMEN
Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities. We examined the effects of oral administration of squalene or squalane on a PD mouse model, which was developed by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA). Squalene administration 7 days before and 7 days after one 6-OHDA injection prevented a reduction in striatal dopamine (DA) levels, while the same administration of squalane enhanced the levels. Neither squalene nor squalane administration for 7 days changed the levels of catalase, glutathione peroxidase, or superoxide dismutase activities in the striatum. Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. These results suggest that the administration of squalene or squalane induces similar changes in the composition of fatty acids and has no effect on the activities of active oxygen scavenging enzymes in the striatum. However, squalane increases oxidative damage in the striatum and exacerbates the toxicity of 6-OHDA, while squalene prevents it. The effects of squalene or squalane treatment in this model suggest their possible uses and risks in the treatment of PD.
Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Ácidos Grasos/metabolismo , Depuradores de Radicales Libres/farmacología , Enfermedad de Parkinson/metabolismo , Escualeno/análogos & derivados , Escualeno/farmacología , Administración Oral , Animales , Catalasa/metabolismo , Modelos Animales de Enfermedad , Depuradores de Radicales Libres/administración & dosificación , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Oxidopamina/toxicidad , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/prevención & control , Escualeno/administración & dosificación , Escualeno/efectos adversos , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
D-Allose, the C-3 epimer of D-glucose, is one of the rare sugars found in nature. In the present study, we have elucidated for the first time that various leukemia cell lines have different susceptibility to anti-proliferative activity of D-allose, and that this difference is related to the difference in induction of thioredoxin interacting protein (TXNIP) expression. We examined 5 leukemia cell lines (MOLT-4F, IM-9, HL-60, BALL-1 and Daudi), and found that MOLT-4F (T-cell lymphoblastic leukemia) had the highest susceptibility to D-allose, and that Daudi (Burkitt's lymphoma) had the lowest. D-Allose significantly slowed the cell cycle progression without causing apoptosis of MOLT-4F cells. Intracellular TXNIP expression was specifically and markedly enhanced in MOLT-4F cells by D-allose treatment, and subsequent increase of p27(kip1), a cell cycle inhibitor, was observed. On the other hand, D-allose did not increase TXNIP and p27(kip1) levels at all in Daudi cells. These results indicate that D-allose suppresses MOLT-4F cell proliferation possibly by the inhibition of cell cycle progression via induction of TXNIP expression.