OXTR-mediated signaling in astrocytes contributes to anxiolysis.

Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo.

Dopamine D2 receptor activation counteracts olfactory dysfunction and related cellular abnormalities in experimental parkinsonism.

Olfactory dysfunction is a common non-motor symptom associated with Parkinson's disease (PD). This condition usually appears before the onset of the cardinal motor symptoms and is still poorly understood. Here, we generated a mouse model of early-stage PD based on partial 6-hydroxydopamine (6-OHDA) lesion of the dorsal striatum to reproduce the olfactory deficit and associated cellular and electrophysiological anomalies observed in patients.

Serotonergic and dopaminergic neurons in the dorsal raphe are differentially altered in a mouse model for parkinsonism.

Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input.

Investigating affective neuropsychiatric symptoms in rodent models of Parkinson's disease.

Affective neuropsychiatric disorders such as depression, anxiety and apathy are among the most frequent non-motor symptoms observed in people with Parkinson's disease (PD). These conditions often emerge during the prodromal phase of the disease and are generally considered to result from neurodegenerative processes in meso-corticolimbic structures, occurring in parallel to the loss of nigrostriatal dopaminergic neurons. Depression, anxiety, and apathy are often treated with conventional medications, including selective serotonin reuptake inhibitors, tricyclic antidepressants, and dopaminergic agonists.

A mouse model of sleep disorders in Parkinson's disease showing distinct effects of dopamine D2-like receptor activation.

Excessive daytime sleepiness (EDS) and sleep fragmentation are often observed in Parkinson's disease (PD) patients and are poorly understood despite their considerable impact on quality of life. We examined the ability of a neurotoxin-based mouse model of PD to reproduce these disorders and tested the potential counteracting effects of dopamine replacement therapy. Experiments were conducted in female mice with a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, leading to the loss of dopamine neurons projecting to the dorsal and ventral striatum.

Lipoproteins as Drug Carriers for Cyclosporine A: Optimization of the Entrapment.

Lipoproteins are natural nanostructures responsible for the transport of cholesterol and other lipids in the blood. They are characterized by having a lipophilic core surrounded by an amphiphilic shell composed of phospholipids, cholesterol and one or more apolipoproteins. Being endogenous carriers makes them suitable for drug delivery purposes.

A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice.

The lateral septum (LS) has been implicated in the regulation of locomotion. Nevertheless, the neurons synchronizing LS activity with the brain's clock in the suprachiasmatic nucleus (SCN) remain unknown. By interrogating the molecular, anatomical and physiological heterogeneity of dopamine neurons of the periventricular nucleus (PeVN; A14 catecholaminergic group), we find that Th/Dat1 cells from its anterior subdivision innervate the LS in mice.

Chronic treatment with hormonal contraceptives alters hippocampal BDNF and histone H3 post-translational modifications but not learning and memory in female rats.

Hormonal contraceptives prevent ovulation with subsequent reduction in endogenous levels of estradiol, progesterone and its neuroactive metabolite allopregnanolone. These neurosteroids modulate several brain functions, including neuronal plasticity, cognition and memory. We hypothesized that hormonal contraceptives might affect synaptic plasticity, learning and memory, as a consequence of suppressed endogenous hormones levels.

A reappraisal of the form - function problem. Theory and phenomenology.

This paper is aimed at demonstrating that some geometrical and topological transformations and operations serve not only as promoters of many specific genetic and cellular events in multicellular living organisms, but also as initiators of the organization and regulation of their functions. Thus, changes in the form and structure of macromolecular and cellular systems must be directly associated to their functions. There are specific classes of enzymes that manipulate the geometry and topology of complex DNA-protein structures, and thereby they perform many important cellular processes, including segregation of daughter chromosomes, gene regulation, and DNA repair.

Geometry and phenomenology of the living: Limits and possibilities of mathematization, complexity and individuation in biological sciences.

The central aim of this Special Issue, devoted to a multifocal study of the geometry and phenomenology of the living, is to show the need of working with models that integrate geometrical and topological objects and operations, dynamical variables and specific biological mechanisms and their relationships with one another. A multilevel and integrative approach has essentially to consider the fact that simply knowing the parts list of genes and proteins does not tell us much about how life's many biological processes works. The cellular organization is a complex dynamical system with hundreds of thousands of bio-molecules interacting with one another to execute organism's many related functions.

Modeling Parkinson's Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers.

The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson's disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes.

Implementation and Evaluation of a Novel High-Value Care Curriculum in a Single Academic Surgery Department.

Background: High value care (HVC), maximizing quality while minimizing cost, has become a major focus of surgical practice. Effective education in healthcare value concepts is critical during residency to ensure graduates are able to deliver high value surgical care and participate in interprofessional teams to improve the system.

Study Design: An HVC curriculum was implemented at a single academic medical center.

Metabolomics Fingerprint Induced by the Intranigral Inoculation of Exogenous Human Alpha-Synuclein Oligomers in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is considered a synucleinopathy because of the intraneuronal accumulation of aggregated α-synuclein (αSyn). Recent evidence points to soluble αSyn-oligomers (αSynO) as the main cytotoxic species responsible for cell death. Given the pivotal role of αSyn in PD, αSyn-based models are crucial for the investigation of toxic mechanisms and the identification of new therapeutic targets in PD.

Advances in modelling alpha-synuclein-induced Parkinson's diseases in rodents: Virus-based models versus inoculation of exogenous preformed toxic species.

Aggregates of alpha-synuclein (αSyn) have been described in Parkinson's disease (PD) patients, and recent evidence has suggested that the most toxic αSyn species in PD are small soluble aggregates including oligomers, prefibrils, protofibrils. The physiological function of αSyn is still highly debated, with a possible role in synaptic vesicle trafficking and release at the presynaptic compartment, and in the regulation of gene expression in the nucleus. Emerging evidence indicate that most of αSyn functions are related with the crucial ability to bind biological membranes, which is associated with structural conversion from a disordered monomer to an α-helical enriched structure.

Neuroprotection by the Immunomodulatory Drug Pomalidomide in the LRRK2 Genetic Model of Parkinson's Disease.

The search for new disease-modifying drugs for Parkinson's disease (PD) is a slow and highly expensive process, and the repurposing of drugs already approved for different medical indications is becoming a compelling alternative option for researchers. Genetic variables represent a predisposing factor to the disease and mutations in leucine-rich repeat kinase 2 (LRRK2) locus have been correlated to late-onset autosomal-dominant PD. The common fruit fly melanogaster carrying the mutation LRRK2 loss-of-function in the WD40 domain (LRRK2), is a simple model of PD and is a valid tool to first evaluate novel therapeutic approaches to the disease.

Treatment with gut bifidobacteria improves hippocampal plasticity and cognitive behavior in adult healthy rats.

At the present time, gut microbiota inspires great interest in the field of neuroscience as a function of its role in normal physiology and involvement in brain function. This aspect suggests a specific gut-brain pathway, mainly modulated by gut microbiota activity. Among the multiple actions controlled by microbiota at the brain level, neuronal plasticity and cognitive function represent two of the most interesting aspects of this cross-talk communication.

Trimethyl Chitosan Hydrogel Nanoparticles for Progesterone Delivery in Neurodegenerative Disorders.

Progesterone is a sex hormone which shows neuroprotective effects in different neurodegenerative disorders, including Parkinson's disease, stroke, and Alzheimer's disease. However, the pharmacokinetic limitations associated with the peripheral administration of this molecule highlight the need for more efficient delivery approaches to increase brain progesterone levels. Since the nose-to-brain administration of mucoadhesive hydrogel nanoparticles is a non-invasive and convenient strategy for the delivery of therapeutics to the central nervous system, in this work, progesterone-loaded hydrogel nanoparticle formulations have been prepared, characterized, and tested in vivo.

Assessing the Training Costs and Work of Diagnostic Radiology Residents Using Key Performance Indicators - An Observational Study.

Rationale And Objectives: To quantify the costs and work of diagnostic radiology (DR) residents using the radiology key performance indicator turn-around time (TAT) as the outcome measure.

Materials And Methods: In an Institutional Review Board-approved study, the annual cost of a DR resident was determined using salary, benefits, and a cost allocation of faculty effort. The volume of cases reported in the 2015-16 academic year and median and interquartile range (IQR) TAT for a trainee preliminary (Complete to Prelim, C-P) or an attending final (Complete to Final, C-F) radiology report were measured and stratified by time of day and patient location.

Immunomodulatory drugs alleviate l-dopa-induced dyskinesia in a rat model of Parkinson's disease.

Background: Thalidomide and closely related analogues are used clinically for their immunomodulatory and antiangiogenic properties mediated by the inhibition of the proinflammatory cytokine tumor necrosis factor α. Neuroinflammation and angiogenesis contribute to classical neuronal mechanisms underpinning the pathophysiology of l-dopa-induced dyskinesia, a motor complication associated with l-dopa therapy in Parkinson's disease. The efficacy of thalidomide and the more potent derivative 3,6'-dithiothalidomide on dyskinesia was tested in the 6-hydroxydopamine Parkinson's disease model.

Financial Analysis of Pediatric Resident Physician Primary Care Longitudinal Outpatient Experience.

Objective: To determine whether residency training represents a net positive or negative cost to academic medical centers, we analyzed the cost of a residency program and clinical productivity of residents and faculty in an outpatient primary care practice with or without residents.

Methods: Patient volume and revenue data (Current Procedural Terminology codes) from an academic primary care general pediatric clinic were evaluated for faculty clinics (faculty only) and resident teaching clinics (longitudinal outpatient experience [LOE]) with 1 to 4 residents per faculty. A detailed cost per resident was determined using a departmental financial model that included salary, benefits, faculty and administrative staff effort, nonpersonnel costs, and institutional graduate medical education support.

Microglial Phagocytosis and Its Regulation: A Therapeutic Target in Parkinson's Disease?

The role of phagocytosis in the neuroprotective function of microglia has been appreciated for a long time, but only more recently a dysregulation of this process has been recognized in Parkinson's disease (PD). Indeed, microglia play several critical roles in central nervous system (CNS), such as clearance of dying neurons and pathogens as well as immunomodulation, and to fulfill these complex tasks they engage distinct phenotypes. Regulation of phenotypic plasticity and phagocytosis in microglia can be impaired by defects in molecular machinery regulating critical homeostatic mechanisms, including autophagy.

Boosting phagocytosis and anti-inflammatory phenotype in microglia mediates neuroprotection by PPARγ agonist MDG548 in Parkinson's disease models.

Background And Purpose: Microglial phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). PPARγ agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548.

Neuroinflammation in L-DOPA-induced dyskinesia: beyond the immune function.

Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration.

Binary Solvent Extraction of Tocols, γ-Oryzanol, and Ferulic Acid from Rice Bran Using Alkaline Treatment Combined with Ultrasonication.

Alkaline treatment (Alk) combined with ultrasound-assisted extraction (UAE) (Alk+UAE) was examined as a means of extracting tocols and γ-oryzanol from rice bran into an organic phase while simultaneously recovering ferulic acid into an aqueous phase. The tocols and γ-oryzanol/ferulic acid yields were determined using high-performance liquid chromatography with fluorescence and UV detection. The effects of extraction conditions were evaluated by varying the Alk treatment temperature and extraction duration.