RESUMEN
This study investigated the effect of long-term high-fat diet (HFD) on plasma lipid profile and probability of inflammation in adult rats. After weaning, male offspring were divided into six groups based on diet type and medication. After 20 weeks of dietary intake, 4-PBA (endoplasmic reticulum (ER) stress inhibitor) was injected for three days. Then, blood samples were taken to measure plasma concentrations of low-density lipoprotein (LDL), triglyceride (TG), high-density lipoprotein (HDL), cholesterol, leptin and interleukin 1-ß (IL 1-ß). The HFD increased body weight and food intake and intra-abdominal fat and thymus weights, which were associated with elevated plasma leptin level. Moreover, HFD increased plasma concentrations of TG, LDL, cholesterol and IL 1-ß and decreased HDL level. Injection of 4-PBA reversed the plasma parameters changes caused by HFD. It seems that long-term HFD feeding through inducing the ER stress, disrupted the lipid metabolism and resulted in inflammation.
Asunto(s)
Dieta Alta en Grasa , Leptina , Ratas , Masculino , Animales , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Colesterol , Inflamación/etiología , Triglicéridos , Estrés del Retículo Endoplásmico , Interleucina-1RESUMEN
Huntington disease (HD) is a progressive neurological disorder with dominant motor symptoms. It also has psychiatric manifestations, like anxiety and depression, that can emerge themselves before motor symptoms and impose a major burden on patients. Oxytocin (OXT) is a newly emerged treatment for disorders like autism and schizophrenia and recently is using to alleviate depression and anxiety. In the current study, we investigated the behavioral and molecular effects of OXT on the development of anxiety and depression in 3-nitropropionic acid (3-NP)-induced model of HD. Anxiety- and depression-like behaviors as well as the levels of oxytocin receptor (OXTR), metabotropic glutamate receptor (mGluR) 2, mGluR5, and glutathione (GSH) were measured in striatum, hippocampus, prefrontal cortex, and amygdala. Also, we questioned if sex had any modulatory effect. We found that 3-NP increased anxiety and depression compared to controls. It also reduced the levels of OXTR and mGluR2, increased mGluR5, and reduced GSH in studied brain regions. Pretreatment with OXT before the injection of 3-NP ameliorated anxiety and depression. Additionally, it protected the brain from developing low levels of OXTR, mGluR2, and GSH and high levels of mGluR5 in studied regions. The protective effects of OXT were similar between male and female animals. These data suggest that OXTR, mGluR2, mGluR5, and GSH may contribute to psychiatric manifestations of HD. In addition, pretreatment with OXT could prevent the mood changes in male and female rats.
Asunto(s)
Receptores de Glutamato Metabotrópico , Receptores de Oxitocina , Animales , Ansiedad/complicaciones , Ansiedad/tratamiento farmacológico , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Femenino , Masculino , Oxitocina/farmacología , RatasRESUMEN
Impairment in the energetic function of mitochondria is seen in many neurologic disorders like neurodegeneration. It disrupts ATP production, gives rise to oxidative stress, and ultimately challenges the viability of neurons. In this situation, neural cells use complex crosstalk between various subcellular elements to make live-or-die decisions about their fate. This study aimed to describe a part of the molecular changes and the outcome of the cellular decision during an energy crisis in neural cells in a time-dependent manner in the striatum. Adult male rats were treated with single or multiple 3-nitropropionic acid (3-NP) doses, a mitochondrial toxin, for 1 to 5 days. We found that protein disulfide isomerase (PDI) activity was decreased on the third day and remained lower than the control group up to the fifth day. However, on the day 1 and day 2 of 3-NP treatment, the stromal interaction molecule (STIM) 1 and STIM2 significantly decreased. On the third day, STIM1 and STIM2 were increased and reached the level of controls and remained the same up to the fifth day. In this condition, cell death was significantly higher than the controls from the third day up to the fifth day. We also showed that even a single dose of 3-NP reduced the brain volume. These data suggest that the STIM1, STIM2, and PDI activity changes may be involved in the outcome of cellular fate decisions. It also suggests that cells may reduce STIM1 and STIM2 as a defense mechanism against low energy availability.
Asunto(s)
Metabolismo Energético/efectos de los fármacos , Nitrocompuestos/toxicidad , Propionatos/toxicidad , Proteína Disulfuro Isomerasas/metabolismo , Transducción de Señal/efectos de los fármacos , Molécula de Interacción Estromal 1/metabolismo , Molécula de Interacción Estromal 2/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Convulsivantes/toxicidad , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Metabolismo Energético/fisiología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/fisiología , Ratas , Ratas Wistar , Transducción de Señal/fisiologíaRESUMEN
Evidence has validated the prophylactic effects of exercising on different aspects of health. On the opposite side, immobilization may lead to various destructive effects causing neurodegeneration. Here, we investigated the association between exercising and mitochondrial quality for preventing the destructive effects of restraint stress in different rat brain regions. Twenty-four male Wistar rats, were randomized into four groups (n = 6), exercise, stress, exercise + stress, and control. The exercise procedure consisted of running on a rodent treadmill for 8 weeks, and rats in the stress group were immobilized for 6 h. Rats were then euthanized by decapitation and tricarboxylic acid (TCA) cycle enzyme activity, antioxidant levels, and mitochondrial biogenesis factors were assessed in the frontal, hippocampus, parietal and temporal regions using spectrophotometer and western blot technique. Based on our results, increased activity of TCA cycle enzymes in the exercised and exercise-stressed groups was detected, except for malate dehydrogenase which was decreased in exercise-stressed group, and fumarase that did not change. Furthermore, the level of antioxidant agents (superoxide dismutase and reduced glutathione), mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial transcription factor A), and dynamics markers (Mitofusin 2, dynamic related protein 1, PTEN induced putative kinase-1, and parkin) increased in both mentioned groups. Interestingly our results also revealed that the majority of the mitochondrial factors increased in the frontal and parietal lobes, which may be in relation with the location of motor and sensory areas. Exercise can be used as a prophylactic approach against bioenergetics and mitochondrial dysfunction.
Asunto(s)
Encéfalo/metabolismo , Metabolismo Energético , Dinámicas Mitocondriales , Condicionamiento Físico Animal , Restricción Física , Estrés Psicológico/metabolismo , Animales , Antioxidantes/metabolismo , Encéfalo/enzimología , Encéfalo/patología , Ciclo del Ácido Cítrico , Masculino , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Complejo Piruvato Deshidrogenasa/metabolismo , Ratas WistarRESUMEN
Learning and memory impairment manifests years before the onset of motor impairments in Huntington's disease (HD). Oxytocin (OXT), as a neurohypophyseal neuropeptide has a key role in both learning and memory. Hence, we investigated possible protective effect of OXT on instrumental fear conditioning memory impairment by 3-Nitropropionic acid (3-NP) induced HD, considering sex and prenatal stress effects. Pregnant Wistar rats were exposed to restraint stress for 45 min three times a day, from the gestational day 8 to parturition. 3-NP was injected intraperitoneally (20 mg/kg) for 5-7 days after OXT (10 µg/µl. icv) injection in the male and female offspring rats respectively. One day after the last 3-NP injection, the rotarod and passive avoidance task were conducted. As the key molecular determinants in metabolism and memory processes, we measured the activity of acetylcholinesterase (AChE) and the amount of receptor interacting protein3 (RIP3) in the hippocampus, prefrontal cortex, striatum and amygdala using spectrophotometry and western blotting respectively. Besides, the activity of glutamate dehydrogenase was measured (GDH) as a chain between metabolism and memory formation. The results indicated that OXT improved learning and memory impairment caused by 3-NP or prenatal stress in both sexes. It was along with a significant decrease in the level of RIP3, AChE and GDH activities. However, in the presence of prenatal stress, the OXT could improve 3-NP induced learning and memory impairments just in female rats. So it could be suggested as an effective neurotherapeutic agent in diseases such as HD, but its sex and context dependency should be considered carefully.
Asunto(s)
Encéfalo/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Enfermedad de Huntington/complicaciones , Oxitocina/farmacología , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Caracteres Sexuales , Estrés Psicológico/complicaciones , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Encéfalo/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Condicionamiento Operante/efectos de los fármacos , Condicionamiento Operante/fisiología , Modelos Animales de Enfermedad , Miedo/fisiología , Femenino , Enfermedad de Huntington/inducido químicamente , Enfermedad de Huntington/etiología , Masculino , Neurotoxinas/administración & dosificación , Nitrocompuestos/administración & dosificación , Oxitocina/administración & dosificación , Embarazo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Propionatos/administración & dosificación , Ratas , Ratas Wistar , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Peroxisomes are single membrane cell organelles with a diversity of metabolic functions. Here we studied the peroxisomal dysfunction and oxidative stress after 3-nitropropionic acid (3-NP) induced neurotoxicity and the possible protective effects of oxytocin. Adult male and female rats were subjected to OXT and/or 3-NP treatment. The antioxidant enzymes, Superoxide dismutase (SOD) and Catalase (CAT) activities as well as expression level of Peroxin 14 (Pex14), a marker for peroxisomal number and Peroxisomal membrane protein of 70 kDa (PMP70), a metabolic transporter in peroxisome in different brain regions of both sexes were studied. The results indicated that 3-NP significantly decreased the expression level of Pex14 and PMP70 in various studied areas in male and female rats. In addition, 3-NP reduced the SOD and CAT activity in different brain regions in both sexes. OXT treatment increased the expression level of peroxisomal proteins Pex14 and PMP70 which are representative of peroxisome performance improvement. Besides, it ameliorated the antioxidant system capability through increasing the activity of the SOD and CAT in all studied brain regions including Striatum, Hippocampus, Prefrontal Cortex and Amygdala with no differences in male and female rats. This study demonstrated that toxin 3-NP, could ultimately cause peroxisomal malfunction and so determines the contribution of peroxisomal dysfunction in the etiology of HD pathology. OXT significantly increased peroxisomal function and antioxidant system defense capability, therefore illustrates that OXT might be an alternate treatment approach for the neurodegenerative diseases like HD.
RESUMEN
Primary squamous cell carcinoma of the endometrium (PSCCE) is a rare entity, with fewer than 100 cases reported in the literature. We report two cases of PSCCE and review the literature regarding associated markers and treatment outcomes. Many different markers have been tested for association with PSCCE, with mixed results. Thus, it is likely that several etiologic factors are responsible for the development of PSCCE. Further, due to the rarity of the condition, the optimal postoperative management of patients with PSCCE remains to be defined.