СИНТЕЗ И ИССЛЕДОВАНИЕ ИК–ЛЮМИНЕСЦЕНЦИИ ТВЕРДЫХ РАСТВОРОВ (Y1-xYbx)3Al5O12 ПРИ ЛАЗЕРНОМ ВОЗБУЖДЕНИИ

This research work is dedicated to research and development of luminescent properties of solid solutions (Y1-xYbx)3Al5O12 with laser excitation. The spectra of infrared luminescence excited by a laser beam with a wavelength of 0.94 microns. The analysis of the luminescence spectra obtained for solid solutions with different concentrations of ytterbium ions in the composition, and the dependences of the luminescence intensity of the activator composition. Found that in the concentration range of ytterbium ions in the (0.03 £ x £ 0.09), there is a significant increase in the intensity of the luminescence in the 1036 nm and reaches a maximum. With further increase in the concentration of ytterbium ions in the range (0.09 £ x £ 0.115), a decrease in the intensity of luminescence. Decrease in the intensity of luminescence caused by the action of migration and multipole interactions between the ions of ytterbium. And this is due to the fact that at higher concentrations, the probability of recombination energy between ytterbium ions and various quenching centers. Change in the concentration of ytterbium ions has also a strong influence on the kinetic characteristics of the infrared luminescence of solid solutions (Y1-xYbx)3Al5O12.When the concentration of the activator to 0.03 mole fractions of the afterglow time constant (t) increases monotonically from 1040 μs to 1120 μs. With a further increase in the content of the activator in the solid solution, t decreases monotonically and the activator concentration of 0.15 mole fractions of 744 microseconds. Solid solutions (Y1-xYbx)3Al5O12 with maximum intensity infrared luminescence in the band 1036 mm damping constant of about 794 μs.Исследованы люминесцентные свойства твердых растворов (Y1-xYbx)3Al5O12 при лазерном возбуждении. Получены спектры ИК-люми несценции при возбуждении лазерным излучением с длиной волны 0,94 мкм. Проведен анализ спектров люминесценции для твердых растворов с различной концентрацией ионов иттербия в составе и установлены зависимости интенсивности люминесценции от активаторного состава. Установлено, что в диапазоне концентраций ионов иттербия в составе (0,03 £ x £ 0,09) происходит значительное увеличение интенсивности люминесценции в области 1032 нм и достигает максимума. При дальнейшем увеличении концентрации ионов иттербия в диапазоне (0,09 £ x £ 0,115) наблюдается уменьшение интенсивности люминесценции. Уменьшение интенсивности люминесценции вызвано действием мультипольных и миграционных взаимодействий между ионами иттербия, а также тем, что при повышенных концентрациях возрастает вероятность рекомбинации энергии между ионами иттербия и различными тушащими центрами. Установлено, что изменение концентрации ионов иттербия оказывает также сильное влияние на кинетические характеристики ИК-люминесценции твердых растворов (Y1-xYbx)3Al5O12. При увеличении концентрации активатора до 0,03 мольных долей постоянная времени послесвечения t монотонно увеличивается с 1040 до 1120 мкс. При дальнейшем увеличении содержания активатора в составе твердого раствора t монотонно уменьшается и при концентрации активатора, равной 0,15 мольных долей, составляет 744 мкс. Для твердых растворов (Y1-xYbx)3Al5O12 с максимальной интенсивностью ИК-люминесценции в полосе 1032 мкм постоянная затухания составляет примерно 794 мкс

Preclinical MicroRNA Program for Major Depressive Disorder

Trabajo presentado en el 2nd Annual Oligonucleotides for CNS Summit, celebrado en Boston (Estados Unidos), del 13 al 15 de junio de 202

Oligonucleotides as therapeutic tools for brain disorders: Focus on major depressive disorder and Parkinson's disease

Remarkable advances in understanding the role of RNA in health and disease have expanded considerably in the last decade. RNA is becoming an increasingly important target for therapeutic intervention; therefore, it is critical to develop strategies for therapeutic modulation of RNA function. Oligonucleotides, including antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA mimic (miRNA), and anti-microRNA (antagomir) are perhaps the most direct therapeutic strategies for addressing RNA. Among other mechanisms, most oligonucleotide designs involve the formation of a hybrid with RNA that promotes its degradation by activation of endogenous enzymes such as RNase-H (e.g., ASO) or the RISC complex (e.g. RNA interference - RNAi for siRNA and miRNA). However, the use of oligonucleotides for the treatment of brain disorders is seriously compromised by two main limitations: i) how to deliver oligonucleotides to the brain compartment, avoiding the action of peripheral RNAses? and once there, ii) how to target specific neuronal populations? We review the main molecular pathways in major depressive disorder (MDD) and Parkinson's disease (PD), and discuss the challenges associated with the development of novel oligonucleotide therapeutics. We pay special attention to the use of conjugated ligand-oligonucleotide approach in which the oligonucleotide sequence is covalently bound to monoamine transporter inhibitors (e.g. sertraline, reboxetine, indatraline). This strategy allows their selective accumulation in the monoamine neurons of mice and monkeys after their intranasal or intracerebroventricular administration, evoking preclinical changes predictive of a clinical therapeutic action after knocking-down disease-related genes. In addition, recent advances in oligonucleotide therapeutic clinical trials are also reviewed.This study was supported by grants SAF2016-75797-R and PID2019-105136RB-I00, Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (ERDF), UE (to A.B.); and CB/07/09/0034 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). We thank M. Calvo and E. Coll for outstanding technical support in the confocal microscopy unit (CCiT-UB). We also thank M. Jaramillo for helpful secretarial assistance. Fig. 1, Fig. 3 were generated using online application Motifolio Illustration Toolkits.com and Created with BioRender.com, respectively.Peer reviewe

Dnmt3a in the Medial Prefrontal Cortex Regulates Anxiety-Like Behavior in Adult Mice

Recently, it has been suggested that alterations in DNA methylation mediate the molecular changes and psychopathologies that can occur following trauma. Despite the abundance of DNA methyltransferases (Dnmts) in the brain, which are responsible for catalyzing DNA methylation, their roles in behavioral regulation and in response to stressful challenges remain poorly understood. Here, we demonstrate that adult mice which underwent chronic social defeat stress (CSDS) displayed elevated anxiety-like behavior that was accompanied by a reduction in medial prefrontal cortex (mPFC)-DNA methyltransferase 3a (Dnmt3a) mRNA levels and a subsequent decrease in mPFC-global DNA methylation. To explore the role of mPFC-Dnmt3a in mediating the behavioral responses to stressful challenges we established lentiviral-based mouse models that express lower (knockdown) or higher (overexpression) levels of Dnmt3a specifically within the mPFC. Nonstressed mice injected with knockdown Dnmt3a lentiviruses specifically into the mPFC displayed the same anxiogenic phenotype as the CSDS mice, whereas overexpression of Dnmt3a induced an opposite, anxiolytic, effect in wild-type mice. In addition, overexpression of Dnmt3a in the mPFC of CSDS mice attenuated stress-induced anxiety. Our results indicate a central role for mPFC-Dnmt3a as a mediator of stress-induced anxiety

miR-135 as a New Target for Antidepressant Therapy: Preclinical Study

Trabajo presentado en el FENS Forum 2022, celebrado en París (Francia), del 9 al 13 de julio de 202