Intracerebroventricular Administration of Mineralocorticoid Receptor Antisense Oligonucleotides Attenuates Salt Appetite in the Rat

The anterior ventral third ventricle (AV3V) region of the brain contains high concentrations of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) that are important in the maintenance of body fluid and electrolyte balance as well as other physiological processes. Daily intracerebroventricular pulse injections of MR antisense oligonucleotides significantly suppressed deoxycorticosterone acetate (DOCA) induced salt appetite in a dose-related manner. Similar administration of GR antisense or scrambled/sense oligonucleotide into the third ventricle failed to inhibit salt appetite. Salt appetite aroused after adrenalectomy was not suppressed by MR antisense oligonucleotide treatments but was suppressed by an antisense oligonucleotide directed against the angiotensin II AT1 receptor subtype. Receptor binding analysis demonstrated that MR and GR oligonucleotide treatments each reduced their respective receptor subtypes. Finally, although GR antisense oligonucleotide treatment was ineffective in suppressing DOCA-induced salt appetite, this treatment did increase stress induced corticosterone release as well as delayed the recovery of corticosterone to basal levels after stress.     

Energetic Cost and Stability During Human Walking at the Preferred Stride Velocity

The possibility that preferred modes of locomotion emerge from dynamical and optimality constraints and the energetic and dynamical constraints on preferred and predicted walking frequency are explored in this article. Participants were required to walk on a treadmill at their preferred frequency, at a frequency predicted as the resonance of a hybrid pendulum-spring model of the legs, and at frequencies +/-15%, +/-25%, +/-35% of the predicted frequency. Walking at the preferred and predicted frequencies resulted in minimal metabolic costs and maximal stability of the head and joint actions. Mechanical energy conservation was constant across conditions. The head was more stable than the joints. The joints appeared to be in service of the head in maintaining a stable trajectory. The major findings of this study suggest a complementary relationship between energetic (physiological) and stability constraints in the adoption of a preferred frequency of walking. Multiple subsystems may be involved in constraining observed macroscopic behavior in intact biological systems. The approach and results of the study imply that a useful tack in understanding how dynamical control structures arise is to study the potential criteria that serve to act as constraints on skilled movement patterns in unimpaired and impaired populations.     

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs

Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.