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Signaling pathways mediated by corticotropin-releasing factor and its receptor 1 (CRF1) play a central role in stress responses. Dysfunction of the CRF system has been associated with neuropsychiatric disorders. However, dynamic changes in the CRF system during brain development and aging are not well investigated. In this study, we characterized CRF1, CRF, and corticotropin-releasing factor binding protein (CRFBP) expression in different brain regions in both male and female C57BL/6J mice from 1 to 18 months of age under basal conditions as well as after an acute 2-hr-restraint stress. We found that CRF and CRF1 levels tended to increase in the hippocampus and hypothalamus, and to decrease in the prefrontal cortex with aging, especially at 18 months of age, whereas CRFBP expression followed an opposite direction in these brain areas. We also observed area-specific sex differences in the expression of these three proteins. For example, CRF expression was lower in females than in males in all the brain regions examined except the prefrontal cortex. After acute stress, CRF and CRF1 were up-regulated at 1, 6, and 12 months of age, and down-regulated at 18 months of age. Females showed more robust changes compared to males of the same age. CRFBP expression either decreased or remained unchanged in most of the brain areas following acute stress. Our findings suggest that brain CRF1, CRF, and CRFBP expression changes dynamically across the lifespan and under stress condition in a sex- and regional-specific manner. Sex differences in the CRF system in response to stress may contribute to the etiology of stress-related neuropsychiatric disorders.There is growing demand for learning developmental biology in Latin America and a need for advanced students to interact with world leaders of this discipline. This article summarizes some of the efforts that Latin America is doing to satisfy the demand in training the young Latin American minds for the developmental biology of the future. I focus on a particular course that has been linked to the origins of the Latin America Society of Developmental Biology (LASDB). I describe the motivations to start organizing this course twenty years ago, its history and setbacks. We tracked back the current situation of former students to find out that more than 90% are still doing developmental biology all across the globe. I describe the state of affairs of the course on its current location in the CIMARQ campus of the Universidad Andres Bello (UNAB), in a place called Quintay on the Chilean coast and I ask about its future.This article provides a brief account of the career of Eugenia M. del Pino. Casual events and serendipity played important roles in modeling her career as developmental biologist. In collaboration with colleagues and students, she analyzed the biology and development of the marsupial frog Gastrotheca riobambae (family Hemiphractidae) in comparison with Xenopus laevis and tropical frogs. The emphasis was placed on oogenesis and the early stages of development. Topics include the mono- and multi-nucleated modes of oogenesis. She described two modes of gastrulation in frogs, gastrulation modes one and two according to the timing of notochord elongation. She was able to establish a pioneer laboratory for the comparative analysis of frog development in Ibero America at the Pontifical Catholic University of Ecuador, in Quito. Her contributions to society include her influence in the establishment of the National Academy of Sciences of Ecuador, and efforts toward the conservation of the Galápagos Archipelago. She is part of a pioneer group of professors that placed Biology as an academic discipline in Ecuador. The experiences of her career reveal that we all face difficulties in our jobs. However, nothing is impossible when we follow a passion. Her work reveals that the key to success is to turn obstacles into opportunities.In this interview, we talk with developmental biologist Eddy De Robertis about his wider scientific career and the history of developmental biology in South America. We discuss the early days of the homebox, the discovery of the mechanism of Spemann organizer function in Xenopus embryos, and related Evo-Devo. De Robertis reflects on trends of how conducting biological research has changed over the years and he provides advice for young scientists.The Latin American Society for Developmental Biology (LASDB) is one of the newest societies in this field. However, despite being new, this society already had a highly important impact on the advancement of Developmental Biology across Latin America and globally. TP0427736 From its conception, the society began with the establishment of courses and congresses at the frontiers of knowledge and with the participation of researchers from Latin American countries and other regions, creating an academic and fraternal environment. The first LASDB congress was held in 2003, and recently, in 2019, the LASDB celebrated its tenth meeting, besides the Pan-American congress organized in 2007. Since the creation of this society and throughout its consolidation, the LASDB has been fortunate in receiving the support of highly prominent Developmental Biology societies, with which it has established links and collaboration that have clearly promoted Development Biology not only in Latin America but also in other parts of the world. At this moment, the LASDB looks to the future to continue supporting science in Latin America as it has done up to the present.
An innovative intranasal aqua-triggered in-situ (ATIS) gel is a polymer-free in-situ gelling microemulsion which gels instantaneously on contact with minute quantities of water to form a mucoadhesive gel. The objective of the study was to develop ATIS diazepam (ATIS-diazepam) as an alternative to the injection for epileptic emergencies and evaluate its brain uptake and nose-to-brain targeting efficiency in rats.
ATIS-diazepam (1mg/100 µL) was prepared and characterized for in vitro formulation characteristics. An LC-MS/MS method was developed and validated for the bioanalysis of diazepam. In vivo studies for pharmacokinetics, brain uptake and nasal irritation of intranasal ATIS-diazepam were conducted in rats. Brain uptake was investigated with brain microdialysis, a highly sensitive technique enabling quantification of free drug, which correlates to efficacy.
ATIS-diazepam exhibited globule size < 200nm, low viscosity, negative zeta potential and good stability. A significant increase in mucoadhesion was exhibited by ATIS-diazepam following the addition of a small quantity of water.