RESUMEN
The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well-established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within the BLA governs these modulatory effects. However, most current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a low-arousing, hippocampal-dependent task. Our experiments combined a weak object location task (OLT) version with subsequent mild predator odor exposure (POE). To investigate the role of endogenous NA in the BLA in memory modulation, a subset of the animals (Wistar rats) was treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected 90 min after drug infusion or after the OLT test, which was performed 24 h later. We used the obtained samples to estimate the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc)-two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE has the potential to become a valuable behavioral paradigm for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.
Asunto(s)
Complejo Nuclear Basolateral , Emociones , Hipocampo , Consolidación de la Memoria , Norepinefrina , Odorantes , Ratas Wistar , Animales , Consolidación de la Memoria/fisiología , Consolidación de la Memoria/efectos de los fármacos , Complejo Nuclear Basolateral/metabolismo , Complejo Nuclear Basolateral/fisiología , Complejo Nuclear Basolateral/efectos de los fármacos , Masculino , Ratas , Norepinefrina/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiología , Hipocampo/efectos de los fármacos , Emociones/fisiología , Emociones/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Propranolol/farmacologíaRESUMEN
INTRODUCTION: Spermatozoa are rapidly changing cellular structures that are highly dependent on their interaction with the environment. These interactions cause fundamental changes in the spermatozoa's cells and membrane.
Asunto(s)
Peptidil-Dipeptidasa A , Semen , Humanos , Masculino , Análisis de Semen , Espermatozoides , TestículoRESUMEN
Testicular angiotensin converting enzyme (ACE) is known to play an essential role in the male reproduction and fertility. Data about tACE in cases of male infertility are quite scarce, and in this respect we aimed to study localization and distribution of tACE protein in the neck and mid-piece of spermatozoa from pathological samples in relation to sperm motility. The enzyme expression during capacitation and acrosome reaction was quantitatively assessed. In human ejaculated spermatozoa tACE is localized on sperm plasma membrane of the head, the neck and mid-piece of the tail. The immunoreactivity becomes stronger in capacitated spermatozoa followed by a decrease in acrosome reacted sperm. In different cases of semen pathology (oligozoospermia, asthenozoospermia and teratozoospermia) fluorescent signals in the neck and mid-piece are in punctate manner whereas in normozoospermia they were uniformly distributed. The expression area of tACE the neck and mid-piece was decreased in ejaculated and capacitated sperm from pathological semen samples compared to normospermia. Significant positive correlation was established between tACE area and progressive sperm motility, whereas with immotile sperm the correlation was negative. Our data suggest that proper distribution of tACE in the neck and mid-piece is required for normal sperm motility that could be used as a novel biomarker for male infertility.
Asunto(s)
Infertilidad Masculina/enzimología , Peptidil-Dipeptidasa A/metabolismo , Pieza Intermedia del Espermatozoide/enzimología , Motilidad Espermática/fisiología , Testículo/enzimología , Acrosoma/enzimología , Adulto , Eyaculación , Humanos , Masculino , Persona de Mediana Edad , Semen/metabolismo , Capacitación Espermática , Adulto JovenRESUMEN
Evidence has accumulated that the pathology of CoViD-19 is strongly related to the renin-angiotensin system (RAS). The blockage of the angiotensin converting enzyme 2 (ACE2) by the SARS-CoV-2 virus leads to downstream consequences such as increased vascular tone, extensive fibrosis and pronounced immune reactions. Different approaches to tackle the adverse viral effects by compensating the lost ACE2 function have been suggested. Here, we use an unequal-arm lever model to describe a simplified version of the biased regulation exercised by the angiotensin II and angiotensin-(1-7) hormones, which are the substrate and the product of ACE2, respectively. We reason upon the lever dynamics and its disruptions caused by the virus, and propose that a combination of RAS modulators will most efficiently compensate the imbalance due to the excess of angiotensin II and the scarcity of angiotensin-(1-7). Specifically, we focus on the possible benefits of the simultaneous application of two agents, a MAS-receptor agonist and an angiotensin-II-type-2-receptor agonist. We conjecture that this combination has the potential to introduce a beneficial synergistic action that promotes anti-hypoxic, anti-fibrotic and anti-proliferative effects, thereby improving the clinical management of acute and chronic CoViD-19 pathologies.
Asunto(s)
Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Tratamiento Farmacológico de COVID-19 , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Sistema Renina-Angiotensina/efectos de los fármacos , Angiotensina I , Angiotensina II , Humanos , Fragmentos de Péptidos , Proto-Oncogenes MasRESUMEN
The objective of the present study was to assess the impact of cobalt (Co) exposure on tissue distribution of iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn), as well as serum hepcidin levels in immature mice (18, 25, 30 days). Pregnant mice were exposed to 75 mg/kg b.w. cobalt chloride (CoCl2 × 6H2O) with drinking water starting from 3 days before delivery and during lactation. At weaning (day 25) the offspring were separated and housed in individual cages with subsequent exposure to 75 mg/kg b.w. CoCl2 until 30 days postnatally. Evaluation of tissue metal levels was performed by an inductively coupled plasma-mass spectrometry (ICP-MS). Serum hepcidin level was assayed by enzyme linked immunosorbent assay (ELISA). Cobalt exposure resulted in a time- and tissue-dependent increase in Co levels in kidney, spleen, liver, muscle, erythrocytes, and serum on days 18, 25, and 30. In parallel with increasing Co levels, CoCl2 exposure resulted in a significant accumulation of Cu, Fe, Mn, and Zn in the studied tissues, with the effect being most pronounced in 25-day-old mice. Cobalt exposure significantly increased serum hepcidin levels only in day18 mice. The obtained data demonstrate that Co exposure may alter essential metal metabolism in vivo.
Asunto(s)
Cobalto/toxicidad , Metales/metabolismo , Efectos Tardíos de la Exposición Prenatal , Envejecimiento , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Cobalto/farmacocinética , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Metales/toxicidad , Ratones , Ratones Endogámicos ICR , Músculo Esquelético/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Bazo/efectos de los fármacos , Bazo/patologíaRESUMEN
Developing brain is very sensitive to the influence of environmental factors during gestation and the neonatal period. The aim of the study is to assess cobalt and iron accumulation in the brain as well as changes in the expression of iron-regulatory proteins transferrin receptor 1, hepcidin, and ferroportin in suckling mice. Perinatal exposure to cobalt chloride increased significantly cobalt content in brain tissue homogenates of 18-day-old (d18) and 25-day-old (d25) mice inducing alterations in brain iron homeostasis. Higher degree of transferrin receptor 1 expression was demonstrated in cobalt chloride-exposed mice with no substantial changes between d18 and d25 mice. A weak ferroportin expression was found in 18-day-old control and cobalt-treated mouse brain. Cobalt exposure of d25 mice resulted in increased ferroportin expression in brain compared to the untreated age-matched control group. Hepcidin level in cobalt-exposed groups was decreased in d18 mice and slightly increased in d25 mice. The obtained data contribute for the better understanding of metal toxicity impact on iron homeostasis in the developing brain with further possible implications in neurodegeneration.
Asunto(s)
Encéfalo/metabolismo , Cobalto/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Proteínas Reguladoras del Hierro/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Cobalto/metabolismo , Femenino , Hepcidinas/genética , Hepcidinas/metabolismo , Hierro/metabolismo , Proteínas Reguladoras del Hierro/genética , Ratones , Ratones Endogámicos ICR , Embarazo , Efectos Tardíos de la Exposición Prenatal , Receptores de Transferrina/genética , Receptores de Transferrina/metabolismoRESUMEN
The mammalian zona pellucida (ZP) is an extracellular glycoprotein structure formed around growing oocytes, ovulated eggs and preimplantation embryos. The specific functions of ZP are highly determined by its morphological structure. Studies on cat oocytes during maturation and after fertilization were undertaken, using routine transmission (TEM) and scanning electron microscopy (SEM). Two basic ZP layers - outer with rough spongy appearance and inner with smaller fenestrations and smooth fibrous network - were visible. Deposits, secreted by oviductal cells formed new layer, the so called oviductal ZP. After fertilization outer ZP showed rougher meshed network due to fusion between filaments as a consequence from sperm penetration while the inner was smoother with melted appearance. The presented data on the SEM and TEM characteristics of cat oocytes, together with our previous studies on carbohydrate distribution suggest that during oocyte maturation and fertilization ZP undergoes structural and functional rearrangements related to sperm binding and penetration.