In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation.

High fat diets have been used as complementary treatments for seizure disorders for more than a century. Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.

Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation.

The hormone ghrelin displays several well-characterized functions, including some with pharmaceutical interest. The receptor for ghrelin, the growth hormone secretagogue receptor (GHSR), is expressed in the hypothalamic paraventricular nucleus (PVH), a critical hub for the integration of metabolic, neuroendocrine, autonomic, and behavioral functions. Here, we performed a neuroanatomical and functional characterization of the neuronal types mediating ghrelin actions in the PVH of male mice.

Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels.

Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson's disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expression in the plasma membrane. Here, we show that similar to SCAMP2, the co-expression of SCAMP5 in tsA-201 cells expressing recombinant Ca3.

Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (Ca) Subtypes in mPFC Neurons.

The dopamine receptor type 1 (D1R) and the dopamine receptor type 5 (D5R), which are often grouped as D1R-like due to their sequence and signaling similarities, exhibit high levels of constitutive activity. The molecular basis for this agonist-independent activation has been well characterized through biochemical and mutagenesis in vitro studies. In this regard, it was reported that many antipsychotic drugs act as inverse agonists of D1R-like constitutive activity.

Constitutive activity of the dopamine (D ) receptor, highly expressed in CA1 hippocampal neurons, selectively reduces Ca 3.2 and Ca 3.3 currents.

Background And Purpose: Ca 3.1-3 currents differentially contribute to neuronal firing patterns. Ca 3 are regulated by G protein-coupled receptors (GPCRs) activity, but information about Ca 3 as targets of the constitutive activity of GPCRs is scarce.

Ghrelin treatment induces rapid and delayed increments of food intake: a heuristic model to explain ghrelin's orexigenic effects.

Ghrelin is a stomach-derived peptide hormone with salient roles in the regulation of energy balance and metabolism. Notably, ghrelin is recognized as the most powerful known circulating orexigenic hormone. Here, we systematically investigated the effects of ghrelin on energy homeostasis and found that ghrelin primarily induces a biphasic effect on food intake that has indirect consequences on energy expenditure and nutrient partitioning.

Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms.

Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via the growth hormone secretagogue receptor (GHSR), which is highly expressed in the brain. Strikingly, the accessibility of ghrelin to the brain seems to be limited and restricted to few brain areas. Previous studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier, an interface constituted by the choroid plexus and the hypothalamic tanycytes.

Ghrelin Selectively Inhibits Ca3.3 Subtype of Low-Voltage-Gated Calcium Channels.

The mechanisms by which ghrelin controls electrical activity in the hypothalamus are not fully understood. One unexplored target of ghrelin is Ca3, responsible for transient calcium currents (T-currents) that control neuronal firing. We investigated the effect of ghrelin on Ca3 subtypes and how this modulation impacts on neuronal activity.

Inter-individual Variability for High Fat Diet Consumption in Inbred C57BL/6 Mice.

Since inbred C57BL/6 mice are known to show inter-individual phenotypic variability for some traits, we tested the hypothesis that inbred C57BL/6 mice display a different tendency to consume a high fat (HF) diet. For this purpose, we used a compilation of HF intake data from an experimental protocol in which satiated mice were exposed to a HF pellet every morning for 2-h over 4 consecutive days. We found that mice displayed a large degree of variability in HF intake.

Evidence Supporting a Role for the Blood-Cerebrospinal Fluid Barrier Transporting Circulating Ghrelin into the Brain.

The stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice have shown that the accessibility of ghrelin into the brain is limited and that it mainly takes place in some circumventricular organs, such as the median eminence. Notably, some known brain targets of ghrelin are distantly located from the circumventricular organs.

Ghrelin receptor signaling targets segregated clusters of neurons within the nucleus of the solitary tract.

Ghrelin is a stomach-derived hormone that regulates a variety of biological functions such as food intake, gastrointestinal function and blood glucose metabolism, among others. Ghrelin acts via the growth hormone secretagogue receptor (GHSR), a G-protein-coupled receptor located in key brain areas that mediate specific actions of the hormone. GHSR is highly expressed in the nucleus of the solitary tract (NTS), which is located in the medulla oblongata and controls essential functions, including orofacial, autonomic, neuroendocrine and behavioral responses.

Mechanisms associated with the effects of urea on the micellar structure of sodium dodecyl sulphate in aqueous solutions.

We used simulations by Molecular Dynamics to characterize the mechanism whereby the variations in the urea concentration modifies the micellar structure of sodium dodecyl sulfate monomers in water. From a self-assembled micellar system, we observed that increasing urea concentration leads to a decrease in aggregation number. Likewise, when increasing urea concentration, the micelles increase their nonpolar surface exposed to solvent, while the polar surface exposed to solvent decreases.

Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice.

Ghrelin is a potent orexigenic peptide hormone that acts through the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor highly expressed in the hypothalamus. In vitro studies have shown that GHSR displays a high constitutive activity, whose physiological relevance is uncertain. As GHSR gene expression in the hypothalamus is known to increase in fasting conditions, we tested the hypothesis that constitutive GHSR activity at the hypothalamic level drives the fasting-induced hyperphagia.

Neuroendocrine Regulation of Metabolism.

Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism.

A further contribution to the knowledge of two inadequately known species of geophilid centipedes from the Andes of South-Central Chile, currently assigned to the genus Plateurytion Attems, 1909 (Chilopoda: Geophilomorpha).

Two poorly known species of geophilid centipedes from the Andes of South-Central Chile, i.e., Plateurytion mundus (Chamberlin, 1955) and Plateurytion zapallar (Chamberlin, 1955) (Myriapoda: Chilopoda: Geophilomorpha), are herein redescribed and illustrated after type specimens of both taxa and new material of the latter, rectifying the condition of the coxosternites of the second maxillae, which are medially joined through a narrow, hyaline and non-areolate membranous isthmus only (instead of "broadly fused as in Pachymerium", as stated by Chamberlin), this being consistent with the current generic assignment of these species under Plateurytion Attems, 1909.

Mathematical modelling of fluid transport and its regulation at multiple scales.

Living matter equals water, to a first approximation, and water transport across barriers such as membranes and epithelia is vital. Water serves two competing functions. On the one hand, it is the fundamental solvent enabling random mobility of solutes and therefore biochemical reactions and intracellular signal propagation.

A new schendylid centipede (Myriapoda: Chilopoda: Geophilomorpha) from the Bolivian Amazon Forest.

Schendylops grismadoi sp. nov., a new schendylid centipede (Chilopoda: Geophilomorpha) from the Amazon forest of east-central Bolivia (Santa Cruz Department, Guarayos Province) is described and illustrated based on the holotype female.

First report of geophilid centipedes of the genus Ribautia (Myriapoda: Chilopoda: Geophilomorpha) from the Atlantic Forest biome, with description of a new miniature species from Misiones Province, Northeastern Argentina.

Ribautia paranaensis sp. nov. a new miniature species of geophilid centipede from the Upper Paraná Atlantic Forest (the westernmost of the fifteen ecoregions comprising the Atlantic Forest biome sensu Di Bitetti et al.

Further contribution to the knowledge of Ityphilus calinus Chamberlin, 1957, a poorly known ballophilid centipede from Colombia, with description of Ityphilus bonatoi, a new diminutive geophilomorph species from Brazil (Myriapoda: Chilopoda, Geophilomorpha).

Ityphilus calinus Chamberlin, 1957 (Chilopoda: Geophilomorpha, Ballophilidae), a poorly known centipede from Cauca Valley, Colombia, is herein redescribed and illustrated after the male holotype, revealing the condition of the forcipular tarsungulum (which is completely smooth), also giving new data on many other morphological features of specific value until now unknown. A new diminutive species named Ityphilus bonatoi sp. nov.