A service-learning educational approach developed the transversal competencies of undergraduate students in an outreach workshop aimed to high school students

In the last decade, research institutes and universities have strengthened the development of outreach activities in the biomedical field, involving researchers and professors as well as graduate students, but with little or no implication of undergraduate students. The development of this type of activities, using the Service-Learning educational approach, could be a valuable tool that would manage the acquisition of learning competencies by undergraduate students of Health Science Degrees and would put science at the service of society.In this project, we present the development of the workshop entitled “Exploring the human body”, in which 205 students in their first and second year of a Degree in Nursing or Medicine (University of Málaga, Spain) acted as mentors of 753 high school students (15 to 16 years old) in several school years (since 2016-2017, excluding 2019-2020 and 2020-2021 due to the COVID-19 pandemic). The workshop consisted of five work stations. Each station featured a set of different experiments and activities that were designed to teach the multiple levels by which the human body, and particularly the nervous system, can be studied: biomolecules, cells, tissues, organs and systems. Both high school and undergraduate students gave an evaluation of the workshop via questionnaires (Likert scale-based and short-answer questions) and a debriefing with the university professors. Data showed an overall score of 4.6 Out of 5 points for the workshop by both high school and undergraduate students. In addition, undergraduate students pointed out that their participation had a positive impact on their academic background (4.8 Out of 5 points), mainly due to the improvement of their oral communication skills (78 students) and self-confidence (58 students). Therefore, these results suggest that this methodology would be valid and applicable to develop the transversal competences of the students in Bachelor's degrees of Health Sciences.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Impact of the glutamatergic neurotransmission within the A5 region on the cardiorespiratory response evoked from the midbrain dlPAG

Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20–50 μA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5–10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (p < 0,001) and tachycardia (p < 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (p < 0,01, p < 0,001, p < 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (p < 0,01; p < 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.Funding for open access publishing: Universidad Málaga/CBUA // The study was supported by a program grant Junta de Andalucía, Group nº CTS-156, Spain

Pharmacological activation of dopamine D4 receptor prevents morphine-induced impairment of the subventricular adult neurogenesis: functional implications in odor discrimination learning.

Morphine reduces adult neurogenesis in the subventricular zone (SVZ) and therefore the integration of newly generated neurons in the local olfactory bulb (OB) circuit. However, the effects of opioids drugs on the olfactory perception have been scarce studied, although some data suggests that they interfere with olfactory function. We have previously shown that the activation of the dopamine D4 receptor (D4R) prevents both morphine addiction -by modulating dopamine signaling from nigral dopamine cells- and the development of morphine-induced analgesic tolerance -by regulating the primary circuit of pain and GABA/glutamate balance within the dorsal horn. Here, we hypothesize that the D4R could also counteract the impairment of olfaction associated with morphine. We investigated the effect of chronic paradigm of combined treatment of morphine with the D4R agonist PD168,077 on SVZ neurogenesis in adult rats using immunohistochemistry and its functional implications by an olfactory discrimination test. Results showed that, in the SVZ, D4R activation counteracted morphine-induced depletion of newly generated glial cells (astrocytes and oligodendrocytes) and neuroblasts as well as the increase of tyrosine hydroxylase expression. Besides, three weeks of chronic administration of morphine impaired olfactory discrimination between a pair of odorants, which was completely prevented by the co-administration with PD168,077. The present results give support for the existence of antagonistic functional D4R-MOR interaction in olfactory bulb and SVZ that could help to the development of new pharmacology strategies for the treatment of pain reducing side-effects of morphine.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. CTS161, Junta de Andalucía UMA20-FEDERJA-122, Junta de Andalucí

Laryngeal effects of stimulation of the dorsolateral Periaqueductal Grey Matter in spontaneously breathing anaesthetized rats

The stimulation of the Periaqueductal Gray matter (PAG) and nucleus retroambiguus (nRA) produces vocalization. A high expression of FOXP2 protein at mesencephalic (PAG) and pontine regions involved in cardiorespiratory control has been described. The aim of this study was to characterize the possible role of the dlPAG in modulating laryngeal activity and their effects on vocalization. Experimental studies were carried out with non-inbred male rats (n=27), Sprague-Dawley (250-300 g). Animals were anesthetized with sodium pentobarbitone (60 mg/kg i.p., initial dose, supplemented 2mg/ kg, i.v., as necessary). Neuromorphological study (n=6) The pattern of staining for c-Fos and FOXP2 protein immunoreactivity (c-Fos-ir) were examinated throughout the rostrocaudal extent of the nRa/nA region during electrical stimulation of the dlPAG. Neuropharmacological study (n=21) A double tracheal cannulation was used to obtain an “isolated glottis in situ” and to record respiratory airflow. Bilateral parietostomy allowed access to the dlPAG. Electrical stimulations (n=7) of this region using concentric bipolar electrodes (1ms pulses, 20-40µA, 100Hz for 5s) were performed. Microinjections of PBS-Evans Blue (250nl, pH 7.4±0.1, 5-s duration) (n=7) or glutamate (0,25M, 250nl) (n=7) were performed. Respiratory flow, pleural pressure, blood pressure and heart rate were also recorded. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in nRA/nA somatas (p<0.01) and confirm the expression of FOXP2 bilaterally in both nuclei. dlPAG PBS-Evans Blue microinjections did not produce any significant changes in any of the cardiorespiratory variables recorded. dlPAG stimulations evoked a decrease of laryngeal resistance (subglottal pressure) (p<0,001) accompanied with an inspiratory facilitatory response consisted of an increase in respiratory rate (p<0,001), together with a pressor (p<0,001) and tachycardic response (p<0,001).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Dorsolateral Periaqueductal Grey Matter in the control of laryngeal activity and subglottic pressure in spontaneously breathing anaesthetized rats.

The stimulation of the dlPAG produces vocalization. The nRA turn passive into active expiration modifying the activity of laryngeal motoneurons located in the nA. We have shown that cPB and A5 Region are involved in changes of laryngeal caliber. A high expression of FOXP2 protein at mesencephalic and pontine regions involved in cardiorespiratory control has been described. The aim is to characterize the role of the dlPAG in modulating laryngeal activity and their effects on vocalization. Experimental studies were carried out with male Sprague-Dawley rats (n=25) (250-300g). Animals were anesthetized with sodium pentobarbitone (60 mg/kg i.p., initial dose, supplemented 2 mg/kg, i.v.). The pattern of staining for c-Fos and FOXP2 protein immunoreactivity were examinated throughout the rostrocaudal extent of the nRa/nA region during electrical stimulation of the dlPAG. Electrical stimulations (n=7) (1ms pulses, 20-40μA, 100Hz for 5s), microinjections of PBS-Evans Blue (250nl, pH 7.4±0.1, 5-s duration) (n=7) or glutamate (0,25M, 250nl) (n=7) were performed. Respiratory flow, pleural pressure, subglottic pressure, blood pressure and heart rate were recorded. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in nRA/nA somatas (p<0.01) and confirm the expression of FOXP2 bilaterally in both nuclei. dlPAG PBS-Evans Blue microinjections did not produce any significant changes in any of the cardiorespiratory variables recorded. dlPAG electrical and chemical (glutamate) stimulations evoked a decrease of laryngeal resistance (subglottal pressure) (p<0,001) accompanied with an inspiratory facilitatory response consisted of an increase in respiratory rate (p<0,001), together with a pressor (p<0,001) and tachycardic response (p<0,001). Our study contributes with new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Service-learning educational approach for undergraduate students: development of an outreach workshop for high school students

In the last decade, research institutes and universities have strengthened the development of outreach activities in the biomedical field, involving researchers and professors as well as graduate students, but with little or no implication of undergraduate students. However, the development of this type of activities, using the Service-Learning educational approach, could be a valuable tool that would manage the acquisition of learning competencies by undergraduate students of Health Science Degrees and would put science at the service of society. In this project, we present the development of the workshop entitled “Exploring the human body”, in which 205 students in their first and second year of a Degree in Nursing or Medicine (University of Málaga, Spain) acted as mentors of 753 high school students (15 to 16 years old) in several school years (since 2016-2017, excluding 2019-2020 and 2020-2021 due to the COVID-19 pandemic). The workshop consisted of five work stations. Each station featured a set of different experiments and activities that were designed to teach the multiple levels by which the human body, and particularly the nervous system, can be studied: biomolecules, cells, tissues, organs and systems. Both high school and undergraduate students gave an evaluation of the workshop via questionnaires (Likert scale-based and short-answer questions) and a debriefing with the university professors. Data showed an overall score of 4.6 out of 5 points for the workshop by both high school and undergraduate students. In addition, undergraduate students pointed out that their participation had a positive impact on their academic background (4.8 out of 5 points), mainly due to the improvement of their oral communication skills (78 students) and self-confidence (58 students).Universidad de Málaga. Servicio de Publicaciones y Divulgación Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Antioxidant and neuroprotective actions of IGF-II against glucocorticoid-induced toxicity in dopaminergic neurons.

The neurodegenerative Parkinson’s disease (PD) affects 1–3% of the population aged over 65. A wide range of pathways and mechanisms are involved in its pathogenesis, such as oxidative stress, mitochondrial dysfunction, inflammation and neuronal glucocorticoid-induced toxicity, which ultimately produce a progressive loss of nigral dopamine neurons. Insulin-like growth factor II (IGF-II) has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Therefore, our aim was to study IGF-II protective effects against oxidative damage on a cellular combined model of PD and mild to moderate stress, based on corticosterone (CORT), an endocrine response marker to stress, and the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). The dopaminergic neuronal cell line SN4741 (RRID:CVCL_S466) derived from mouse substantia nigra were exposed to 200 μM MPP+, 0.5 μM CORT or both, with or without 25 ng/mL IGF-II, for 2.5 or 6 h. Cell viability, oxidative stress parameters, mitochondrial and dopamine markers and intracellular signaling pathways were evaluated. The administration of MPP+ or CORT individually led to cell damage compared to control situations, whereas the combination of both drugs produced very considerable toxic synergistic effect. IGF-II counteracts the mitochondrial-oxidative damage, protecting dopaminergic neurons from death and neurodegeneration. IGF-II maintained the tyrosine hydroxylase expression and promotes nuclear factor (erythroid-derived 2)-like 2 antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damage and maintaining mitochondrial function. This work revealed the potential neuroprotective role of IGF-II to protect nigral dopamine neurons against mitochondrial-oxidative damage induced by CORT and MPP+ was demonstrated. Thus, IGF-II is a potential therapeutic tool for prevention and treatment of PD patients suffering mild to moderate emotional stress.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

IGF-II treatment prevents the oxidative damage derived by MPP+/MPTP administration in a cellular and animal model of Parkinson’s disease.

El factor de crecimiento de la insulina-II (IGF-II) ha mostrado efectos antioxidantes y neuroprotectores en algunos trastornos neurodegenerativos, como es la Enfermedad de Parkinson (EP). Analizamos el efecto de IGF-II y la implicación de la esfingosina kinasa (SPHK), en la citoarquitectura/función mitocondrial tras provocar daño oxidativo con la administración de la neurotoxina MPTP y su metabolito activo. La línea celular SN4741 se trató con MPP+ solo/en presencia de IGF-II (2 h). Los tratamientos fueron reemplazados por medio/IGF-II (2h), respectivamente. Se estudió: morfología (microscopía electrónica, EM), tasa de consumo de oxígeno (OCR) y muerte celular (LDH). MPTP/probenecid(p) por vía parenteral (35d) indujo un daño progresivo en la vía nigroestriatal dopaminérgica (DA-NSP) de los animales. En los días 36-44, se inyectó vehículo. El grupo control recibió vehículo siguiendo el mismo régimen de administración (1-44d). Otro grupo se trató con IGF-II una vez inducido el daño por MPTP (22-44 días). Para investigar el papel de IGF-II en la alteración conductual inducida por MPTP/p, se evaluó el rendimiento motor. Se realizó inmunotinción para marcadores dopaminérgicos y astrogliosis. Las células tratadas con MPP+ mostraron menos mitocondrias (EM) y con pérdida parcial/total de crestas, alteraciones de membrana y forma hinchada. IGF-II mantuvo el número de mitocondrias con morfología similar al control. La disminución de OCR tras la administración de MPP+ (30%) se recuperó con IGF-II. SPHK está implicada en este mecanismo, como indica su inhibición (MPP++IGF-II+MPA-08 6 veces > LDH vs MPP++IGF-II). En animales, IGF-II recuperó el efecto de MPTP sobre los marcadores DA-NSP y sobre el rendimiento motor. IGF-II contrarresta el aumento del estrés oxidativo y la disfunción mitocondrial inducida por la neurotoxina, el deterioro conductual y la degeneración de DA-NSP. SPHK estaría involucrada en este mecanismo.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

RawData Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Collection of data published in the article: https://hdl.handle.net/10630/23528Spanish Ministry of Economy SAF2016-79008-P, PSI2017-82604-R, PID2020- 114392RB-I00, PDC2021-121566-I0. Junta de Andalucia UMA18-FEDERJA-008, P20_00026, PI-0083-201