Effects of enriched-potassium diet on cardiorespiratory outcomes in experimental non-ischemic chronic heart failure

BACKGROUND: Chronic heart failure (CHF) is a global health problem. Increased sympathetic outflow, cardiac arrhythmogenesis and irregular breathing patterns have all been associated with poor outcomes in CHF. Several studies showed that activation of the renin-angiotensin system (RAS) play a key role in CHF pathophysiology. Interestingly, potassium (K+) supplemented diets showed promising results in normalizing RAS axis and autonomic dysfunction in vascular diseases, lowering cardiovascular risk. Whether subtle increases in dietary K+ consumption may exert similar effects in CHF has not been previously tested. Accordingly, we aimed to evaluate the effects of dietary K+ supplementation on cardiorespiratory alterations in rats with CHF. METHODS: Adult male Sprague-Dawley rats underwent volume overload to induce non-ischemic CHF. Animals were randomly allocated to normal chow diet (CHF group) or supplemented K+ diet (CHF+K+ group) for 6 weeks. Cardiac arrhythmogenesis, sympathetic outflow, baroreflex sensitivity, breathing disorders, chemoreflex function, respiratory- cardiovascular coupling and cardiac function were evaluated. RESULTS: Compared to normal chow diet, K+ supplemented diet in CHF significantly reduced arrhythmia incidence (67.8 ± 15.1 vs. 31.0 ± 3.7 events/hour, CHF vs. CHF+K+), decreased cardiac sympathetic tone (ΔHR to propranolol: - 97.4 ± 9.4 vs. - 60.8 ± 8.3 bpm, CHF vs. CHF+K+), restored baroreflex function and attenuated irregular breathing patterns. Additionally, supplementation of the diet with K+ restores normal central respiratory chemoreflex drive and abrogates pathological cardio-respiratory coupling in CHF rats being the outcome an improved cardiac function. CONCLUSION: Our findings support that dietary K+ supplementation in non-ischemic CHF alleviate cardiorespiratory dysfunction.

On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae)

Cognitive ecologist posits that the more efficiently an animal uses information from the biotic and abiotic environment, the more adaptive are its cognitive abilities. Nevertheless, this approach does not test for natural neurodegenerative processes under field or experimental conditions, which may recover animals information processing and decision making and may explain, mechanistically, maladaptive behaviors. Here, we call for integrative approaches to explain the relationship between ultimate and proximate mechanisms behind social behavior. We highlight the importance of using the endemic caviomorph rodent Octodon degus as a valuable natural model for mechanistic studies of social behavior and to explain how physical environments can shape social experiences that might influence impaired cognitive abilities and the onset and progression of neurodegenerative disorders such as Alzheimer disease. We consequently suggest neuroecological approaches to examine how key elements of the environment may affect neural and cognitive mechanisms associated with learning, memory processes and brain structures involved in social behavior. We propose the following three core objectives of a program comprising interdisciplinary research in O. degus, namely: (1) to determine whether diet types provided after weaning can lead to cognitive impairment associated with spatial memory, learning and predisposing to develop Alzheimer disease in younger ages; (2) to examine if early life social experience has long term effects on behavior and cognitive responses and risk for development Alzheimer disease in later life and (3) To determine if an increase of social interactions in adult degu reared in different degree of social stressful conditions alter their behavior and cognitive responses.

Wnt-5a-regulated miR-101b controls COX2 expression in hippocampal neurons

BACKGROUND: Wnt-5a is a member of the WNT family of secreted lipoglycoproteins, whose expression increases during development; moreover, Wnt-5a plays a key role in synaptic structure and function in the adult nervous system. However, the mechanism underlying these effects is still elusive. MicroRNAs (miRNAs) are a family of small non-coding RNAs that control the gene expression of their targets through hybridization with complementary sequences in the 3' UTR, thereby inhibiting the translation of the target proteins. Several evidences indicate that the miRNAs are actively involved in the regulation of neuronal function. RESULTS: In the present study, we examined whether Wnt-5a modulates the levels of miRNAs in hippocampal neurons. Using PCR arrays, we identified a set of miRNAs that respond to Wnt-5a treatment. One of the most affected miRNAs was miR-101b, which targets cyclooxygenase-2 (COX2), an inducible enzyme that converts arachidonic acid to prostanoids, and has been involved in the injury/inflammatory response, and more recently in neuronal plasticity. Consistent with the Wnt-5a regulation of miR-101b, this Wnt ligand regulates COX2 expression in a time-dependent manner in cultured hippocampal neurons. CONCLUSION: The biological processes induced by Wnt-5a in hippocampal neurons, involve the regulation of several miRNAs including miR-101b, which has the capacity to regulate several targets, including COX-2 in the central nervous system

The functional links between prion protein and copper

Prion diseases are fatal neurodegenerative disorders associated with the conversion of the cellular prion protein (PrPC) into a pathologic isoform. Although the physiological function of PrPC remains unknown, evidence relates PrPC to copper metabolism and oxidative stress as suggested by its copper-binding properties in the N-terminal octapeptide repeat region. This region also reduces copper ions in vitro, and this reduction ability is associated with the neuroprotection exerted by the octarepeat region against copper in vivo. In addition, the promoter region of the PrPC gene contains putative metal response elements suggesting it may be regulated by heavy metals. Here we address some of the evidence that support a physiological link between PrPC and copper. Also, in vivo experiments suggesting the physiological relevance of PrPC interaction with heparan sulfate proteoglycans are discussed.

Molecular biology of the amyloid of Alzheimer's disease. An overview

Alzheimer's disease is a progressive neurodegenerative disorder that affects a significant percentage of elderly individuals. Degenerative nerve cells express atypical proteins, and amyloid is deposited. The hallmark event of Alzheimer's disease is the deposition of amyloid as insoluble fibrous masses in extracellular neuritic plaques and around the walls of cerebral blood vessels. This review will focus on the advances on the knowledge of Alzheimer's amyloid, because it is becoming increasingly clear that the deposition of amyloid on neuritic plaques in the brain represents the earliest and most characteristic pathological feature of Alzheimer's disease. The main component of amyloid is a 4.2-4.5 KDa hydrophobic peptide, named amyloid beta-peptide, that is codified in chromosome 21 as part of a much larger precursor protein. The study of the mechanism by which the amyloid beta-peptide arises from the amyloid precursor protein is very important in order to understand the biological basis of amyloid deposition and its role in Alzheimer's disease

Aspectos biotecnológicos en larvas de "loco" / Biotechnological aspects in \"locus\" larvae

The biology of planktotrophic larvae of Concholepas concholepas is the main bottleneck towards developing biotechnologies to rear this muricid. Data concerning planktonic larvae development, diets and environmental signals triggering larval settlement and recuitment is scarce. We have begun the study of the molecular and cell biology of embryos, larvae and recruits having as a final goal, the development of appropriate biotechnologies to rear this gastropod. First, an inverse ratio between BuChE and AChE enzyme activities was established. This ratio may be a precise development marker for this species. Second, for the first time a phosphoinositide rlated regulatory pathway is reported in a muricid, opening a new approach to the biotechnological management of larvae. Third, the relation between sulfate in sea water and larval motility was studied. Concentration below 125 µM sulfate decreases larval motility. The sulfate is incorporated in proteoglycans which participate in different developmental phenomena. Lastly, a genomic Concholepas concholepas DNA sequence, similar to that of a human growth hormone probe was detected. This is very interesting since growth factors are key molecules during development, growth and are involved in food conversion rares in fishes and also, a in variety of marine invertebrates

The biology of neurofilaments and the degenerative disorders of the central nervous system

Los neurofilamentos son uno de los más importantes componentes de las redes estructurales del citoplasma neuronal. Ellos contienen tres polipeptidos con pesos moleculares de 68.000, 160.000 y 200.000. En esta revisión nosotros discutimos su purificación, propiedades químicas, interacciones moleculares, distribución celular y transporte axonal, como también la posible relación de esta estructura con ciertas enfermedades del sistema nervioso central. En este contexto es interesante mencionar que pacientes con encefalopatías espongiformes y Enfermedad de Alzheimer familiar, presentan títulos altos de autoanticuerpos dirigidos a la subunidad de 200.000 del neurofilamento