Effect of cannabidiol as a neuroprotective agent on neurodevelopmental impairment in rats with neonatal hypoxia.

OBJECTIVE: This study aims to investigate the neuroprotective effects of cannabidiol (CBD) on neurodevelopmental impairments in rats subjected to neonatal hypoxia, specifically examining its potential to mitigate motor and sensory deficits without the confounding effects of ischemia. METHODS: Neonatal Sprague-Dawley rats were allocated to one of four groups: Control, Control-CBD, Hypoxia, and Hypoxia-CBD. Hypoxia was induced on postnatal days 0 and 1. CBD (50 mg/kg) was administered orally for 14 days starting at postnatal day 0. Neurodevelopmental outcomes were assessed using the Neurodevelopmental Reflex Testing in Neonatal Rat Pups scale and the Revised Neurobehavioral Severity Scale for rodents. Statistical analyses were conducted using two-way and one-way ANOVA, with Tukey's post-hoc tests for group comparisons. RESULTS: Pup weights were recorded on specified postnatal days, with no significant differences observed across the groups (p = 0.1834). Significant neurological impairments due to hypoxia were noted in the Control group compared to the Hypoxia group, particularly in hindlimb grasping on postnatal day 3 (p = 0.0025), posture on postnatal day 12 (p = 0.0073), and in general balance and sound reflex on postnatal day 20 (p = 0.0016 and p = 0.0068, respectively). Additionally, a statistically significant improvement in posture was observed in the Hypoxia-CBD group compared to the Hypoxia group alone (p = 0.0024). CONCLUSION: Our findings indicate that CBD possesses neuroprotective properties that significantly counteract the neurodevelopmental impairments induced by neonatal hypoxia in rats. This study not only supports the therapeutic potential of CBD in managing conditions characterized by neurodevelopmental challenges due to hypoxia but also underscores the necessity for further investigation into the specific molecular mechanisms driving CBD's neuroprotective effects. Further research is essential to explore CBD's clinical applications and its potential role in treating human neurodevelopmental disorders.

Psychological impact of sociodemographic factors and medical conditions in older adults during the COVID-19 pandemic in Mexico / Impacto psicológico de factores sociodemográficos y condiciones médicas en adultos mayores durante la pandemia de COVID-19 en México

Abstract Introduction Older adults are not only at a higher medical risk during the COVID-19 pandemic, but they may also be a group particularly vulnerable to mental health diminishing. Objective To analyze the effect of some sociodemographic factors (sex and age) and medical conditions (diabetes and hypertension) on mental health and concerns about COVID-19 in a sample of older adults. Method A non-probabilistic sample of 2,992 older adults (37.7% men and 62.3% women) was selected, with an average age of 70.45 years (SD = 7.31). Participants were given the Impact of Event Scale-6 (IES-6), the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), a questionnaire of concerns about COVID-19, and a sociodemographic questionnaire. Participants' answers were captured via Google Forms. Results The results showed that women had greater concerns about COVID-19 than men. The findings in general showed significant effects, with women showing higher scores in depressive symptoms, anxiety, and greater stress generated in addition by the impact of the event. Differences concerning event-related stress and depression were found in relation to subgroups by age. Discussion and conclusion These finding could serve for the planning and development of strategies that provide attention to the mental health of this population group.

Resumen Introducción Los adultos mayores no sólo presentan un mayor riesgo médico durante la pandemia de COVID-19, sino que también pueden ser particularmente vulnerables a la disminución de la salud mental. Objetivo Analizar el efecto de algunos factores sociodemográficos (sexo y edad) y condiciones médicas (diabetes e hipertensión) sobre la salud mental y las preocupaciones sobre COVID-19 en una muestra de adultos mayores. Método Se seleccionó una muestra no probabilística de 2,992 adultos mayores (37.7% hombres y 62.3% mujeres), con una edad promedio de 70.45 años (DE = 7.31). Los participantes recibieron la Estala de Impacto de Evento-6, el Cuestionario de Salud del Paciente-9, el Trastorno de Ansiedad Generalizada-7, un cuestionario de preocupaciones sobre COVID-19 y un cuestionario sociodemográfico. Resultados Las mujeres presentaron mayores preocupaciones por COVID-19 que los hombres. Las respuestas de los participantes se capturaron en Google Forms. Resultados En general, los hallazgos mostraron efectos significativos, siendo las mujeres quienes presentaron puntuaciones más altas en síntomas depresivos y ansiedad, así como mayor estrés asociado a evento. Además, se encontraron efectos diferenciados por subgrupos de edad en relación con estrés asociado a evento y síntomas depresivos. Discusión y conclusión Estos hallazgos pudieran ser útiles para planificar y desarrollar estrategias que brinden atención a la salud mental de este grupo de población.

Desarrollo Positivo en Jóvenes Involucrados en Voluntariado y su Relación con las Neuronas Espejo / Positive Development in Young People Involved in Volunteering and Its Relation to Mirror Neurons / Desenvolvimento Positivo em Jovens Envolvidos em Voluntariado e sua Relação com os Neurônios Espelho

Resumen En este estudio se analizó el efecto del desarrollo positivo sobre la contribución en jóvenes, y se identificaron las diferencias entre los jóvenes que han realizado actividades de voluntariado y los que no las han realizado; además se analizó la activación de las neuronas espejo. Participaron 121 universitarios, 28.9% hombres y 71.1% mujeres, con una media de edad de 21.51 años. Se utilizó la escala de Desarrollo Positivo en Adolescentes y de Contribución, además de un instrumento conformado por dos conjuntos de estímulos visuales. Los resultados corroboraron el efecto de las 5 c's sobre la contribución y se encontraron diferencias significativas en la escala de carácter y en dos dimensiones de contribución, donde los jóvenes que realizan actividades de voluntariado puntuaron más alto que aquellos que no las realizan. Se comprobó que existe activación en la zona correspondiente a las neuronas espejo, lo cual se relaciona con procesos empáticos. Se concluye que existe una relación entre las actividades de voluntariado y el desarrollo positivo en jóvenes universitarios.

Abstract The study analyzed the effect of positive development on contribution in young people and identified the differences between those who have done volunteer work and those who have not. It also studied the activation of the mirror neurons system. Participants were 121 university students, 28.9% male and 71.1% female, with an average age of 21.51. The Positive Youth Development Scale and the Contribution Scale were used, in addition to an instrument made up of two sets of visual stimuli. The results confirmed the effect of the 5 Cs on the contribution dimension and significant differences were found in the character scale and in two dimensions of contribution, in which young people who do volunteer work got higher scores than those who do not. The study confirmed that there was activation in the zone corresponding to the mirror neurons system, which is related to empathetic processes, and concluded that there was a relation between volunteering activities and the positive development of university students.

Resumo Neste estudo, foi analisado o efeito do desenvolvimento positivo sobre a contribuição em jovens e foram identificadas as diferenças entre os jovens que realizaram atividades de voluntariado e os que não as realizaram; além disso, foi analisada a ativação dos neurônios espelho. Participaram 121 universitários, 28.9 % homens e 71.1% mulheres, com uma média de idade de 21.51 anos. Foi utilizada a Escala de Desenvolvimento Positivo em Adolescentes e de Contribuição, ainda de um instrumento conformado por dois conjuntos de estímulos visuais. Os resultados corroboraram o efeito das 5 c's sobre a contribuição e foram verificadas diferenças significativas na escala de caráter e em duas dimensões de contribuição, em que os jovens que realizam atividades de voluntariado pontuaram mais alto que aqueles que não as realizam. Foi comprovado que existe ativação na zona correspondente aos neurônios espelho, o que está relacionado com processos empáticos. Conclui-se que existe uma relação entre as atividades de voluntariado e o desenvolvimento positivo em jovens universitários.

Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats.

Aging is associated with morphological, physiological and metabolic changes, leading to multiorgan degenerative pathologies, such as cognitive function decline. It has been suggested that memory loss also involves a decrease in neurotrophic factors, including brain-derived neurotrophic factor (BDNF). In recent years, microbiota has been proposed as an essential player in brain development, as it is believed to activate BDNF secretion through butyrate production. Thus, microbiota modulation by supplementation with probiotics and prebiotics may impact cognitive decline. This study aimed to evaluate the effects of probiotics and prebiotics supplementation on the memory of middle-aged rats. Sprague-Dawley male rats were randomized in four groups (n = 13 per group): control (water), probiotic (E. faecium), prebiotic (agave inulin), symbiotic (E. faecium + inulin), which were administered for 5 weeks by oral gavage. Spatial and associative memory was analyzed using the Morris Water Maze (MWM) and Pavlovian autoshaping tests, respectively. Hippocampus was obtained to analyze cytokines [interleukin (IL-1ß) and tumor necrosis factor (TNF-α)], BDNF and γ-aminobutyric acid (GABA) by enzyme-linked immunosorbent assay (ELISA). Butyrate concentrations were also evaluated in feces. The symbiotic group showed a significantly better performance in MWM (p < 0.01), but not in Pavlovian autoshaping test. It also showed significantly lower concentrations of pro-inflammatory cytokines (p < 0.01) and the reduction in IL-1ß correlated with a better performance of the symbiotic group in MWM (p < 0.05). Symbiotic group also showed the highest BDNF and butyrate levels (p < 0.0001). Finally, we compared the electrophysiological responses of control (n = 8) and symbiotic (n = 8) groups. Passive properties of CA1 pyramidal cells (PCs) exhibited changes in response to the symbiotic treatment. Likewise, this group showed an increase in the N-methyl-D-aspartate receptor (NMDA)/AMPA ratio and exhibited robust long-term potentiation (LTP; p < 0.01). Integrated results suggest that symbiotics could improve age-related impaired memory.

pVHL suppresses Akt/ß-catenin-mediated cell proliferation by inhibiting 14-3-3ζ expression.

The mechanisms controlling degradation of cytosolic ß-catenin are important for regulating ß-catenin co-transcriptional activity. Loss of von Hippel-Lindau protein (pVHL) has been shown to stabilize ß-catenin, increasing ß-catenin transactivation and ß-catenin-mediated cell proliferation. However, the role of phosphoinositide 3-kinase (PI3K)/Akt in the regulation of ß-catenin signaling downstream from pVHL has never been addressed. Here, we report that hyperactivation of PI3K/Akt in cells lacking pVHL contributes to the stabilization and nuclear accumulation of active ß-catenin. PI3K/Akt hyperactivation is facilitated by the up-regulation of 14-3-3ζ and the down-regulation of 14-3-3ε, 14-3-3η and 14-3-3θ. Up-regulation of 14-3-3ζ in response to pVHL is important for the recruitment of PI3K to the cell membrane and for stabilization of soluble ß-catenin. In contrast, 14-3-3ε and 14-3-3η enhanced PI3K/Akt signaling by inhibiting PI3K and PDK1, respectively. Thus, our results demonstrated that 14-3-3 family members enhance PI3K/Akt/ß-catenin signaling in order to increase proliferation. Inhibition of Akt activation and/or 14-3-3 function strongly reduces ß-catenin signaling and decreases cell proliferation. Thus, inhibition of Akt and 14-3-3 function efficiently reduces cell proliferation in 786-0 cells characterized by hyperactivation of ß-catenin signaling due to pVHL loss.

Programmed and induced phenotype of the hippocampal granule cells.

Certain neurons choose the neurotransmitter they use in an activity-dependent manner, and trophic factors are involved in this phenotypic differentiation during development. Developing hippocampal granule cells (GCs) constitutively express the markers of the glutamatergic and GABAergic phenotypes, but when development is completed, the GABAergic phenotype shuts off. With electrophysiological, single-cell reverse transcription-PCR and immunohistological techniques, we show here that short-term (24 h) cultures of fully differentiated adult glutamatergic GCs, which express glutamate, VGlut-1 (vesicular glutamate transporter) mRNA, calbindin, and dynorphin mRNA, can be induced to reexpress the GABAergic markers GABA, GAD67 (glutamate decarboxylase 67 kDa isoform), and VGAT (vesicular GABA transporter) mRNA, by sustained synaptic or direct activation of glutamate receptors and by activation of TrkB (tyrosine receptor kinase B) receptors, with brain-derived neurotrophic factor (BDNF) (30 min). The expression of the GABAergic markers was prevented by the blockade of glutamate receptors and sodium or calcium channels, and by inhibitors of protein kinases and protein synthesis. In hippocampal slices of epileptic rats and in BDNF-treated slices from naive rats, we confirmed the appearance of monosynaptic GABAA receptor-mediated responses to GC stimulation, in the presence of glutamate receptors blockers. Accordingly, GC cultures prepared from these slices showed the coexpression of the glutamatergic and GABAergic markers. Our results demonstrate that the neurotransmitter choice of the GCs, which are unique in terms of their continuing birth and death throughout life, depends on programmed and environmental factors, and this process is neither limited by a critical developmental period nor restricted by their insertion in their natural network.

Synaptic plasticity: understanding the neurobiological mechanisms of learning and memory: part II

Uno de los fenómenos más nteresantes dentro del campo de la neurobiología, es el fenómeno de la plasticidad cerebral relacionada con los eventos de aprendizaje y el procesamiento del fenómeno de memoria. De hecho, estos fenómenos neurobiológicos empezaron a ser estudiados desde principios de siglo. Remotamente, el fenómeno de plasticidad cerebral en relación con el desarrollo y aprendizaje de las conductas fue ya concebido y cuestionado desde hace más de dos centurias. Sin embargo, desde hace cuatro décadas, múltiples evidencias experimentales han demostrado que tanto la experiencia o el entrenamiento en la ejecución de tareas operantes aprendidas, inducen cambios plásticos en la fisiología neuronal, incluyendo los cambios neuroquímicos y moleculares que se requieren para consolidar una memoria a largo plazo. Asimismo, diversos procedimientos experimentales han demostrado que la experiencia diferencial, el entrenamiento y el aprendizaje de conductas o la experiencia informal, producen cambios mensurables en el cerebro de los mamíferos. Más aún, la neuropsicología ha considerado desde hace varias décadas que diferentes tipos de memoria pueden ser localizados en diferentes circuitos neuronales en distintas áreas de la corteza cerebral. Sin embargo, los estudios recientes han demostrado que los sistemas de memoria están distribuidos en circuitos neuronales corticales específicos. Por ejemplo, los mismos sistemas corticales que procesan la percepción sensorial y las función motora, son los mismos sustratos neurales que se emplean para procesar los fenómenos de memorización. El fenómeno de la memoria y el aprendizaje es resultado de la actividad fisiológica repetitiva de millones de neuronas que, ensambladas en circuitos neuronales específicos, conllevan al reforzamiento de las conexiones sinápticas involucradas y a los cambios de plasticidad sináptica que se requieren para establecer estos fenómenos neurobiológicos. El fenómeno de potenciación a largo plazo, o LTP, es un evento neurofisiológico que resulta del incremento en el reforzamiento de la transmisión sináptica, que puede perdurar en las regiones cerebrales estudiadas desde horas a días. El modelo de LTP quizá representa el modelo funcional experimental más viable para entender las bases celulares del aprendizaje y la memoria en el SNC de los mamíferos, incluyendo el cerebro de los humanos.

Synaptic plasticity: Understanding the neurobiological mechanims of learning and memory: part I

Uno de los fenómenos más interesantes dentro del campo de la neurobiología, es el fenómeno de la plasticidad cerebral relacionada con los eventos de aprendizaje y el procesamiento del fenómeno de memoria. De hecho, estos fenómenos neurobiológicos empezaron a ser estudiados desde principios de siglo. Remotamente, el fenómeno de plasticidad cerebral en relación con el desarrollo y aprendizaje de las conductas fue ya concebido y cuestionado desde hace más de dos centurias. Sin embargo, desde hace cuatro décadas, múltiples evidencias experimentales han demostrado que tanto la experiencia o el entrenamiento en la ejecución de tareas operantes aprendidas, inducen cambios plásticos en la fisiología neuronal, incluyendo los cambios neuroquímicos y moleculares que se requieren para consolidar una memoria a largo plazo. Asimismo, diversos procedimientos experimentales han demostrado que la experiencia diferencial, el entrenamiento y el aprendizaje de conductas o la experiencia informal, producen cambios mensurables en el cerebro de los mamíferos. Más aún, la neuropsicología ha considerado desde hace varias décadas que diferentes tipos de memoria pueden ser localizados en diferentes circuitos neuronales en distintas áreas de la corteza cerebral. Sin embargo, los estudios recientes han demostrado que los sistemas de memoria están distribuidos en circuitos neuronales corticales específicos. Por ejemplo, los mismos sistemas corticales que procesan la percepción sensorial y la función motora, son los mismos sustratos neurales que se emplean para procesar los fenómenos de memorización. El fenómeno de la memoria y el aprendizaje es resultado de la actividad fisiológica repetitiva de millones de neuronas que, ensambladas en circuitos neuronales específicos, conllevan al reforzamiento de las conexiones sinápticas involucradas y a los cambios de plasticidad sináptica que se requieren para establecer estos fenómenos neurobiológicos. El fenómeno de potenciación a largo plazo, o LTP, es un evento neurofisiológico que resulta del incremento en el reforzamiento de la transmisión sináptica, que puede perdurar en las regiones cerebrales estudiadas desde horas a días. El modelo de LTP quizá representa el modelo funcional experimental más viable para entender las bases celulares del aprendizaje y la memoria en el SNC de los mamíferos, incluyendo el cerebro de los humanos.