Intrauterine growth restriction (IUGR) and preeclampsia (PE) are leading causes of perinatal and maternal morbidity and mortality. Previously we reported the expression of lipid rafts in classical microvillous membrane (MVM) and light microvillous membrane (LMVM), two subdomains in apical membrane from the human placental syncytiotrophoblast (hSTB), which constitute the epithelium responsible for maternal-fetal transport. Here the aim was to study the raft and cytoskeletal proteins from PE and IUGR. Microdomains from MVM and LMVM were tested with raft markers (placental alkaline phosphatase, lipid ganglioside, and annexin 2) and a nonraft marker (hTf-R). No changes were detected with those markers in whole purified apical membranes in normal, PE, and IUGR pregnancies; however, their patterns of distribution in lipid rafts were different in PE and IUGR. Cholesterol depletion modified their segregation, confirming their presence in lipid rafts, although unlike normal placenta, in these pathologies there is only one type of microdomain. Additionally, the cytoskeleton proteins actin, ezrin, and cytokeratin-7 showed clear differences between normal and pathological membranes. Cytokeratin-7 expression decreased to 50% in PE, and the distribution between LMVM and MVM (~43 and 57%, respectively) changed in both PE and IUGR, in contrast with the asymmetrical enrichment obtained in normal LMVM (~62%). In conclusion, lipid rafts from IUGR and PE have different features compared to rafts from normal placentae, and this is associated with alterations in the expression and distribution of cytoskeletal proteins.

Rapid transitions at HA favor arrhythmogenesis, the latter becoming evident particularly in the Y group on descent. Age-dependent changes of autonomic activity appear to be involved in arrhythmogenesis on transitions at HA.

Our findings suggest that the reduction of Ca(2+)- and Na(+), K(+)-ATPase activities during preeclampsia could be at least partially due to an increased level of lipid peroxidation of the syncytiotrophoblast plasma membranes.

Potassium channels play important physiological roles in human syncytiotrophoblasts (hSTBs) from placenta, an epithelium responsible for maternal-fetal exchange. Basal and apical plasma membranes differ in their lipid and protein composition, and the latter contains cholesterol-enriched microdomains. In placental tissue, the specific localization of potassium channels is unknown. Previously, we described two isolated subdomains from the apical membrane (MVM and LMVM) and their respective microdomains (lipid rafts). Here, we report on the distribution of K(ir)2.1, K(v)2.1, TASK-1, and TREK-1 in hSTB membranes and the lipid rafts that segregate them. Immunoblotting experiments showed that these channels are present mainly in the apical membrane from healthy hSTBs. Apical expression versus basal membrane was 84 and 16% for K(ir)2.1 and K(v)2.1, 60 and 30% for TREK-1, and 74 and 26% for TASK-1. Interestingly, K(v)2.1 showed differences between apical membrane subdomains: 26 ± 8% was located in the LMVM and 59 ± 9% in MVM. In pathological placentas, the expression distribution changed in the basal membrane: preeclampsia shifted to 50% and intrauterine growth restriction to 42% for TASK-1 and both pathologies increased to 25% for K(ir)2.1 and K(v)2.1, K(ir)2.1 appeared to be associated with rafts that were sensitive to cholesterol depletion in healthy, but not in pathological, placentas. K(v)2.1 and TREK-1 emerged in the nonraft fractions. The precise membrane localization of ion channels in hSTB membranes is necessary to understand the physiological events.

No abstract

High altitude (HA) exposure may affect human health and performance by involving the body timing system. Daily variations of melatonin may disrupt by HA exposure, thereby possibly affecting its relations with a metabolic parameter like the respiratory quotient (RQ). Sea level (SL) volunteers (7 women and 7 men, 21.0 ± 2.04 y) were examined for daily changes in salivary melatonin concentration (SMC). Sampling was successively done at SL (Antofagasta, Chile) and, on acute HA exposure, at nearby Caspana (3,270 m asl). Saliva was collected in special vials (Salimetrics Oral Swab, United Kingdom) at sunny noon (SMCD) and in the absence of blue light at midnight (SMCN). The samples were obtained after rinsing the mouth with tap water and were analyzed for SMC by immunoassay (ELISA kit; IBL International, Germany). RQ measurements (n = 12) were realized with a portable breath to breath metabolic system (OxiconTM Mobile, Germany), between 8:00 PM and 10:00 PM, once at either location. At SL, SMCD, and SMCN values (mean ± SD) were, respectively, 2.14 ± 1.30 and 11.6 ± 13.9 pg/ml (p < 0.05). Corresponding values at HA were 8.83 ± 12.6 and 13.7 ± 16.7 pg/ml (n.s.). RQ was 0.78 ± 0.07 and 0.89 ± 0.08, respectively, at SL and HA (p < 0.05). Differences between SMCN and SMCD (SMCN–SMCD) strongly correlate with the corresponding RQ values at SL (r = -0.74) and less tight at HA (r = -0.37). Similarly, mean daily SMC values (SMC) tightly correlate with RQ at SL (r = -0.79) and weaker at HA (r = -0.31). SMCN–SMCD, as well as, SMC values at SL, on the other hand, respectively, correlate with the corresponding values at HA (r = 0.71 and r = 0.85). Acute exposure to HA appears to loosen relations of SMC with RQ. A personal profile in daily SMC variation, on the other hand, tends to be conserved at HA.

Progressive accumulation of α-Synuclein (αSyn) in Lewy bodies (LBs) and loss of dopaminergic (DA) neurons are the hallmark pathological features of Parkinson’s disease (PD). Although currently available in vitro and in vivo models have provided crucial information about PD pathogenesis, the mechanistic link between the progressive accumulation of αSyn into LBs and the loss of DA neurons is still unclear. To address this, it is critical to model LB formation and DA neuron loss, the two key neuropathological aspects of PD, in a relevant in vitro system. In this study, we developed a human midbrain-like organoid (hMBO) model of PD. We demonstrated that hMBOs generated from induced pluripotent stem cells (hiPSCs), derived from a familial PD (fPD) patient carrying αSyn gene (SNCA) triplication accumulate pathological αSyn over time. These cytoplasmic inclusions spatially and morphologically resembled diverse stages of LB formation and were composed of key markers of LBs. Importantly, the progressive accumulation of pathological αSyn was paralleled by the loss of DA neurons and elevated apoptosis. The model developed in this study will complement the existing in vitro models of PD and will provide a unique platform to study the spatiotemporal events governing LB formation and their relation with neurodegeneration. Furthermore, this model will also be beneficial for in vitro screening and the development of therapeutic compounds.

Previous results evidenced acute exposure to high altitude (HA) weakening the relation between daily melatonin cycle and the respiratory quotient. This review deals with the threat extreme environments pose on body time order, particularly concerning energy metabolism. Working at HA, at poles, or in space challenge our ancestral inborn body timing system. This conflict may also mark many aspects of our current lifestyle, involving shift work, rapid time zone crossing, and even prolonged office work in closed buildings. Misalignments between external and internal rhythms, in the short term, traduce into risk of mental and physical performance shortfalls, mood changes, quarrels, drug and alcohol abuse, failure to accomplish with the mission and, finally, high rates of fatal accidents. Relations of melatonin with energy metabolism being altered under a condition of hypoxia focused our attention on interactions of the indoleamine with redox state, as well as, with autonomic regulations. Individual tolerance/susceptibility to such interactions may hint at adequately dealing with body timing disorders under extreme conditions.