Neurobiology of Posttraumatic Stress Disorder (PTSD) and its Frontostriatal Implications: a short review

Throughout its evolutionary course, stress has remained as an adaptive response to stimuli that may jeopardize the integrity of an organism. Within this perspective, we can classify the stressors as psychological,physical or harmful to cardiovascular stability. However, when intense stressful events occur, there is a possibility of developing PTSD. This disorder makes use of the hypothalamic-pituitary-adrenal axis, which is commonly activated during stress and is kept activated even when the stressful stimulus has ended months ago. The consequences of this condition are observed at the neuroendocrine, neurochemical and anatomical level. This review aims to give a brief report of the neurobiology of stress, PTSD, and its implications in various structures,such as the amygdala, hippocampus and prefrontal cortex

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

Evaluación de la nicotina como estímulo aversivo

La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales

Subjective and Real Time: Coding Under Different Drug States

Organisms are constantly extracting information from the temporal structure of the environment, which allows them to select appropriate actions and predict impending changes.  Several lines of research have suggested that interval timing is modulated by the dopaminergic system.  It has been proposed that higher levels of dopamine cause an internal clock to speed up, whereas less dopamine causes a deceleration of the clock.  In most experiments the subjects are first trained to perform a timing task while drug free.  Consequently, most of what is known about the influence of dopaminergic modulation of timing is on well-established timing performance.  In the current study the impact of altered DA on the acquisition of temporal control was the focal question.  Thirty male Sprague-Dawley rats were distributed randomly into three different groups (haloperidol, d-amphetamine or vehicle).  Each animal received an injection 15 min prior to the start of every session from the beginning of interval training.  The subjects were trained in a Fixed Interval (FI) 16s schedule followed by training on a peak procedure in which 64s non-reinforced peak trials were intermixed with FI trials.  In a final test session all subjects were given vehicle injections and 10 consecutive non-reinforced peak trials to see if training under drug conditions altered the encoding of time.  The current study suggests that administration of drugs that modulate dopamine do not alter the encoding temporal durations but do acutely affect the initiation of responding

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understand- ing of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary mela- noma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity

Reproducibility of fluorescent expression from engineered biological constructs in E. coli

We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices.Peer reviewe