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1.
Rev. Fund. Educ. Méd. (Ed. impr.) ; 26(2): 67-73, Abr. 2023. tab
Article in Spanish | IBECS | ID: ibc-220555

ABSTRACT

Introducción: Desde la década de los noventa, muchos docentes han mostrado un creciente interés por las neurociencias y por la pronta aplicación de los hallazgos neurocientíficos a la educación en al aula, lo cual ha acarreado la proliferación de numerosos neuromitos. Objetivo: Evaluar la prevalencia de neuromitos y el conocimiento sobre el funcionamiento del cerebro entre participantes en un programa de perfeccionamiento en educación en ciencias de la salud, todos ellos profesionales de la salud y profesores universitarios. Sujetos y métodos: El 88% de un total de 197 participantes de cuatro cohortes respondió un cuestionario en línea con 21 afirmaciones acerca del funcionamiento del cerebro, entre las cuales había algunos neuromitos. Se realizó un análisis de frecuencias para cada respuesta obtenida en las diferentes cohortes involucradas en el estudio y una comparación en la muestra general utilizando la prueba de chi cuadrado. Resultados: El 76,6% de los participantes respondió correctamente la mayoría de las afirmaciones sobre el conocimiento de la función cerebral y fue capaz de reconocer algunos de los neuromitos planteados. Cuatro aseveraciones (tres neuromitos y una acerca del funcionamiento cerebral) tuvieron un rendimiento por debajo del 50% (29,2%). Éstas fueron respondidas de forma incorrecta por el 56,3%, y alrededor del 15% de los participantes declaró no saber la respuesta correcta; incluso en dos de ellas el desconocimiento superó el 20%. Conclusiones: Un adecuado conocimiento sobre el funcionamiento del cerebro por parte de los profesores puede permitirles reconocer algunos neuromitos que podrían afectar de manera negativa a su práctica pedagógica, influenciando su desempeño y resultados académicos.(AU)


Introduction: Since the 1990s, many teachers have had a growing interest in neuroscience and in the early application of neuroscientific findings to education in the classroom, which has led to the proliferation of numerous neuromyths. Objective: To assess the prevalence of neuromyths and knowledge about the functioning of the brain among participants in an improvement program in Health Sciences Education, all of them health professionals and university professors. Subjects and methods: 88% of a total of 197 participants from four cohorts answered an online questionnaire with 21 sentences about the functioning of the brain, including some neuromyths. A frequency analysis was performed for each response obtained in the different cohorts involved in the study and a comparison in the general sample using the chi-square test. Results: 76.6% of the participants answered most of the statements about knowledge of brain function correctly and were able to recognize some of the neuromyths posed. Four statements (three neuromyths and one about brain function) had a performance below 50% (29.2%). These were answered incorrectly by 56.3%, and around 15% of the participants stated that they did not know the correct answer, even in two of them the ignorance exceeded 20%. Conclusions: An adequate knowledge of the functioning of the brain by teachers can allow them to recognize some neuromyths that could negatively affect their pedagogical practice, influencing their performance and academic results.(AU)


Subject(s)
Humans , Neurosciences , Faculty , Education , Learning , Health Personnel , Cerebrum , Surveys and Questionnaires
2.
Neurobiol Stress ; 13: 100234, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33344690

ABSTRACT

Several lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions. 89 adult male Sprague-Dawley rats received intraperitoneal fasudil injections (10 mg/kg/day) or saline vehicle for 18 days. Some of these animals were daily restraint-stressed from day 5-18 (2.5 h/day). 24 hr after treatments, rats were either evaluated for behavioral tests (active avoidance, anxiety-like behavior and object location) or euthanized for western blot analyses of hippocampal whole extract and synaptoneurosome-enriched fractions. We report that fasudil prevents stress-induced impairments in active avoidance, anxiety-like behavior and novel location preference, with no effect in unstressed rats. Chronic stress reduced phosphorylations of ERK-2 and CREB, and decreased levels of GluA1 and GluN2A in whole hippocampus, without any effect of fasudil. However, fasudil decreased synaptic GluA1 Ser831 phosphorylation in stressed animals. Additionally, fasudil prevented stress-decreased phosphorylation of GSK-3ß at Ser9, in parallel with an activation of the mTORC1/4E-BP1 axis, both in hippocampal synaptoneurosomes, suggesting the activation of the AKT pathway. Our study provides evidence that chronic fasudil treatment prevents chronic stress-altered behaviors, which correlated with molecular modifications of antidepressant-relevant signaling pathways in hippocampal synaptoneurosomes.

3.
Front Pharmacol ; 10: 157, 2019.
Article in English | MEDLINE | ID: mdl-30873030

ABSTRACT

The entactogen MDMA (3,4-methylenedioxy-methamphetamine, "Ecstasy") exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulation of typical entactogenic effects, using analogs derived from the MDMA template, are still not fully understood. Among many possibilities, aromatic halogenation of the phenylalkylamine moiety may favor distribution to the brain due to increased lipophilicity, and sometimes renders psychotropic substances of high affinity for their molecular targets and high potency in humans. In the present work, a new MDMA analog brominated at C(2) of the aromatic ring (2-Br-4,5-MDMA) has been synthesized and pharmacologically characterized in vitro and in vivo. First, binding competition experiments against the SERT-blocker citalopram were carried out in human platelets and compared with MDMA. Besides, its effects on platelet aggregation were performed in platelet enriched human plasma using collagen as aggregation inductor. Second, as platelets are considered an appropriate peripheral model for estimating central serotonin availability, the functional effects of 2-Br-4,5-MDMA and MDMA on ATP release during human platelet aggregation were evaluated. The results obtained showed that 2-Br-4,5-MDMA exhibits higher affinity for SERT than MDMA and fully abolishes both platelet aggregation and ATP release, resembling the pharmacological profile of citalopram. Subsequent in vivo evaluation in rats at three dose levels showed that 2-Br-4,5-MDMA lacks all key MDMA-like behavioral responses in rats, including hyperlocomotion, enhanced active avoidance conditioning responses and increased social interaction. Taken together, the results obtained are consistent with the notion that 2-Br-4,5-MDMA should not be expected to be an MDMA-like substrate of SERT, indicating that aromatic bromination at C(2) modulates the pharmacodynamic properties of the substrate MDMA, yielding a citalopram-like compound.

4.
Front Mol Neurosci ; 11: 283, 2018.
Article in English | MEDLINE | ID: mdl-30174589

ABSTRACT

Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated-at the same time-the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. The aim of our study was to take a multidimensional approach to investigate concomitant behavioral, morphological and molecular changes induced by a single restraint stress exposure (2.5 h) and a recovery period of 6 and 24 h in rats. We found that acute stress elicited a reduced preference to explore an object placed in a novel position (a hippocampal-dependent task). These changes were accompanied by increased activity of LIM kinase I (LIMK; an actin-remodeling protein) and increased levels of NR2A subunits of NMDA receptors. After 6 h of recovery from stress, rats showed similar preference to explore an object placed in a novel or familiar position, but density of immature spines increased in secondary CA1 apical dendrites, along with a transient rise in GluA2 AMPA receptor subunits. After 24 h of recovery from stress, the animals showed a preference to explore an object placed in a novel position, which was accompanied by a normalization of NMDA and AMPA receptor subunits to control values. Our data suggest that acute stress produces reversible molecular and behavioral changes 24 h after stress, allowing a full reestablishment of hippocampal-related memory. Further studies need to be conducted to deepen our understanding of these changes and their reciprocal interactions.Adaptive stress responses are a promising avenue to develop interventions aiming at restoring hippocampal function impaired by repetitive stress exposure.

5.
FEM (Ed. impr.) ; 20(6): 279-286, nov.-dic. 2017. tab
Article in Spanish | IBECS | ID: ibc-169553

ABSTRACT

Introducción. La Escuela de Enfermería de la Universidad de Chile implantó en 2013 un nuevo currículo basado en competencias profesionales. El objetivo de este estudio fue evaluar el impacto de esta innovación curricular a través de la percepción del ambiente educacional de los estudiantes que, durante 2014, cursaban diferentes tipos de currículos, antiguo o innovado. Sujetos y métodos. Estudio transversal de tres cohortes (n = 300), dos con currículo antiguo y otra con currículo innovado, a las cuales se aplicó el cuestionario Dundee Ready Educational Environment Measure (DREEM). Este instrumento fue diseñado para medir la percepción del ambiente educacional y consta de 50 ítems, divididos en cinco subescalas: percepción de la enseñanza, de los profesores y del ambiente de aprendizaje, y autopercepción académica y social. Resultados. Las puntuaciones totales de la percepción del ambiente educacional fueron significativamente mayores en la cohorte con currículo innovado. No se encontraron diferencias significativas entre ambas cohortes con currículo antiguo. De los 50 ítems del cuestionario DREEM, los estudiantes con currículo innovado presentaron 23 ítems con puntuaciones consideradas buenas (media > 3) y sólo dos ítems con puntuaciones preocupantes (media < 2). En cambio, ambas cohortes con currículo antiguo tuvieron 8 y 11 ítems con puntuaciones buenas, y 10 y 7 ítems con puntuaciones preocupantes, respectivamente. Conclusiones. De acuerdo con la percepción de los estudiantes, el proceso de innovación curricular implementado en la Escuela de Enfermería ha logrado corregir aspectos deficitarios del currículo antiguo. Sin embargo, aún es necesario trabajar sobre ciertos aspectos a fin de remediarlos y obtener un efectivo y exitoso proceso enseñanza-aprendizaje (AU)


Introduction. The School of Nursing of the University of Chile implemented in 2013 a new curriculum based on professional skills. The aim of this study was to evaluate the impact of this curricular innovation through the perception of the educational environment of students who, in 2014, experienced different types of curricula, either former or innovated. Subjects and methods. This was a cross-sectional study. Three cohorts (n = 300), two of them with a former curriculum and another with an innovated curriculum, were surveyed with the DREEM questionnaire. This instrument was designed to measure the perception of the educational environment, and consists of 50 items, divided into five sub-scales: perception about teaching, teachers and learning environment, academic and social self-perception. Results. Overall scores of the perception of the educational environment were significantly higher in the innovated curriculum cohort. No differences were detected between both cohorts with former curriculum. Of the 50 items in the DREEM questionnaire, students with an innovated curriculum presented 23 items with scores considered good (mean > 3.0) and only two items with worrying scores (mean < 2.0). Both cohorts with a former curriculum presented 8 and 11 items with scores considered good, and 10 and 7 items with worrying scores, respectively. Conclusions. According to the students' perception, the process of curricular innovation implemented in the School of Nursing has managed to correct deficient aspects of the former curriculum. However, it is still necessary to work on some aspects in order to remedy them and obtain an effective and successful teaching-learning process (AU)


Subject(s)
Humans , Educational Measurement/methods , Self Concept , Education, Nursing/organization & administration , Curriculum/standards , Students, Nursing/statistics & numerical data , Schools, Nursing/organization & administration , Schools, Nursing/statistics & numerical data , Chile , Cross-Sectional Studies/statistics & numerical data , Surveys and Questionnaires , 28599
6.
Neurotox Res ; 32(1): 134-140, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28285345

ABSTRACT

Dopamine oxidation in the pathway leading to neuromelanin formation generates the ortho-quinone aminochrome, which is potentially neurotoxic but normally rapidly converted by DT-diaphorase to nontoxic leukoaminochrome. However, when administered exogenously into rat striatum, aminochrome is able to produce damage to dopaminergic neurons. Because of a recent report that substantia nigra pars compacta (SNpc) tyrosine hydroxylase (T-OH) levels were unaltered by aminochrome when there was cell shrinkage of dopaminergic neurons along with a reduction in striatal dopamine release, the following study was conducted to more accurately determine the role of DT-diaphorase in aminochrome neurotoxicity. In this study, a low dose of aminochrome (0.8 nmol) with or without the DT-diaphorase inhibitor dicoumarol (0.2 nmol) was injected into the left striatum of rats. Intrastriatal 6-hydroxydopamine (6-OHDA, 32 nmol) was used as a positive neurotoxin control in other rats. Two weeks later, there was significant loss in numbers of T-OH immunoreactive fibers in SNpc, also a loss in cell density in SNpc, and prominent apomorphine (0.5 mg/kg sc)-induced contralateral rotations in rats that had been treated with aminochrome, with aminochrome/dicoumarol, or with 6-OHDA. Findings demonstrate that neurotoxic aminochrome is able to exert neurotoxicity only when DT-diaphorase is suppressed-implying that DT-diaphorase is vital in normally suppressing toxicity of in vivo aminochrome, generated in the pathway towards neuromelanin formation.


Subject(s)
Enzyme Inhibitors/therapeutic use , Indolequinones/toxicity , NAD(P)H Dehydrogenase (Quinone)/metabolism , Neurotoxicity Syndromes/etiology , Neurotoxins/toxicity , Animals , Dicumarol/pharmacology , Disease Models, Animal , Male , Oxidation-Reduction/drug effects , Rats , Rats, Sprague-Dawley , Stereotaxic Techniques , Tyrosine 3-Monooxygenase/metabolism
7.
Int J Neuropsychopharmacol ; 20(4): 336-345, 2017 04 01.
Article in English | MEDLINE | ID: mdl-27927737

ABSTRACT

Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudil-treated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.


Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Dendrites/drug effects , Depression/pathology , Depression/prevention & control , Hippocampus/pathology , Pyramidal Cells/ultrastructure , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/therapeutic use , Actin Depolymerizing Factors/metabolism , Animals , Body Weight/drug effects , Dendrites/ultrastructure , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/metabolism , Immobility Response, Tonic/drug effects , Lim Kinases/metabolism , Male , Neuronal Plasticity/drug effects , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Phosphatase 1/metabolism , Pyramidal Cells/drug effects , Rats , Rats, Sprague-Dawley , Restraint, Physical/adverse effects , Swimming/psychology
8.
Rev. méd. Chile ; 144(11): 1479-1485, nov. 2016. tab
Article in Spanish | LILACS | ID: biblio-845471

ABSTRACT

Background: To establish an educational environment that ensures the quality of the teaching-learning process is a challenge for any educational institution. The questionnaire DREEM (Dundee Ready Educational Environment Measure) is used to identify strengths and weaknesses of an educational environment and to compare different medical schools. Aim: To evaluate the changes in the perception of educational environment by students of the Schools of Medicine of the University of Zaragoza, UZar (Spain) and the University of Chile, UCh (Chile) at two points in their curricula. Material and Methods: DREEM questionnaire was answered by 90 students from the UZar and 87 students of the UCh, when they were in the first year (2009) and in the fourth year of their career (2012). Results: At both universities the overall mean scores of DREAM were significantly higher in students in their first year than those obtained in the fourth year (137.5/118.3 for UZar and 128.6/118.8 for UCh). Items with worse perception in the fourth year were observed in subscales Learning Perception and Atmosphere Perception. Items with good evaluation (≥ 3.0) were the subscales Perception of teachers, academic self-perception, perception of Environment and Social Self-perception. Conclusions: The perception of Chilean and Spanish students about their educational environments indicates that the stage of their medical training is more important than the geographical context or educational institution.


Subject(s)
Humans , Young Adult , Schools, Medical , Students, Medical/psychology , Curriculum , Education, Medical, Undergraduate , Educational Measurement , Perception , Social Environment , Spain , Time Factors , Chile , Surveys and Questionnaires , Longitudinal Studies , Statistics, Nonparametric
9.
Cell Mol Life Sci ; 73(18): 3583-97, 2016 09.
Article in English | MEDLINE | ID: mdl-27001668

ABSTRACT

L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in (1) contralateral rotation when the animals are stimulated with apomorphine; (2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; (3) cell shrinkage; (4) significant reduction of dopamine release; (5) significant increase in GABA release; (6) significant decrease in the number of monoaminergic presynaptic vesicles; (7) significant increase of dopamine concentration inside of monoaminergic vesicles; (8) significant increase of damaged mitochondria; (9) significant decrease of ATP level in the striatum (10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease.


Subject(s)
Dopaminergic Neurons/drug effects , Indolequinones/pharmacology , Parkinson Disease/pathology , Adenosine Triphosphate/metabolism , Animals , Behavior, Animal/drug effects , Chromatography, High Pressure Liquid , Corpus Striatum/metabolism , Disease Models, Animal , Dopamine/analysis , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Humans , Indolequinones/chemical synthesis , Indolequinones/chemistry , Male , Mitochondria/drug effects , Mitochondria/metabolism , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Parkinson Disease/metabolism , Parkinson Disease/veterinary , Rats , Rats, Sprague-Dawley , Substantia Nigra/metabolism , Synaptic Vesicles/metabolism , Tyrosine 3-Monooxygenase/metabolism , gamma-Aminobutyric Acid/analysis
10.
Rev Med Chil ; 144(11): 1479-1485, 2016 Nov.
Article in Spanish | MEDLINE | ID: mdl-28394966

ABSTRACT

BACKGROUND: To establish an educational environment that ensures the quality of the teaching-learning process is a challenge for any educational institution. The questionnaire DREEM (Dundee Ready Educational Environment Measure) is used to identify strengths and weaknesses of an educational environment and to compare different medical schools. AIM: To evaluate the changes in the perception of educational environment by students of the Schools of Medicine of the University of Zaragoza, UZar (Spain) and the University of Chile, UCh (Chile) at two points in their curricula. MATERIAL AND METHODS: DREEM questionnaire was answered by 90 students from the UZar and 87 students of the UCh, when they were in the first year (2009) and in the fourth year of their career (2012). RESULTS: At both universities the overall mean scores of DREAM were significantly higher in students in their first year than those obtained in the fourth year (137.5/118.3 for UZar and 128.6/118.8 for UCh). Items with worse perception in the fourth year were observed in subscales Learning Perception and Atmosphere Perception. Items with good evaluation (≥ 3.0) were the subscales Perception of teachers, academic self-perception, perception of Environment and Social Self-perception. CONCLUSIONS: The perception of Chilean and Spanish students about their educational environments indicates that the stage of their medical training is more important than the geographical context or educational institution.


Subject(s)
Curriculum , Education, Medical, Undergraduate , Educational Measurement , Schools, Medical , Students, Medical , Chile , Humans , Longitudinal Studies , Perception , Social Environment , Spain , Statistics, Nonparametric , Students, Medical/psychology , Surveys and Questionnaires , Time Factors , Young Adult
11.
J Neurosci Res ; 93(10): 1476-91, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26010004

ABSTRACT

Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/ß-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not ß-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.


Subject(s)
Cadherins/metabolism , Dendritic Spines/metabolism , Depression/pathology , Hippocampus/pathology , Neurons/ultrastructure , rho-Associated Kinases/metabolism , Animals , Avoidance Learning , Body Weight/physiology , Depression/etiology , Disease Models, Animal , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Neurons/pathology , Rats , Rats, Sprague-Dawley , Statistics, Nonparametric , Stress, Physiological , Sucrose/metabolism , Sweetening Agents/metabolism , Swimming/psychology , beta Catenin/genetics , beta Catenin/metabolism
12.
Int J Neuropsychopharmacol ; 18(10): pyv038, 2015 Mar 26.
Article in English | MEDLINE | ID: mdl-25813018

ABSTRACT

BACKGROUND: Clinically depressed individuals respond to different types of antidepressants, suggesting that different neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not yet available. METHODS: We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or immobilization in adaptable plastic cones. Both models increased anxiety responses evaluated by novelty-suppressed feeding and the elevated plus-maze; increased learned helplessness evaluated by the tail suspension and forced swimming tests; and increased anhedonia evaluated by the sucrose preference test. RESULTS: We assessed the ability of 2 different types of antidepressants to ameliorate depressive-like behaviors. We administered the serotonin reuptake inhibitor fluoxetine or the noradrenaline reuptake inhibitor reboxetine once daily for 28 days to rats that received either chronic restraint or immobilization stress, or no stress. Behavioral analysis revealed that fluoxetine ameliorated depressive-like behaviors when induced by chronic restraint stress, whereas reboxetine ameliorated these behaviors when induced by chronic immobilization stress. To further test biological differences between both models, we evaluated the levels of Aldolase C, an enzyme expressed by forebrain astrocytes that is regulated by antidepressant treatment, in the cerebrospinal fluid: chronic restraint stress, but not immobilization stress, increased the levels of Aldolase C. Moreover, the presence of astrocyte-derived Aldolase C-GFP in the cerebrospinal fluid indicates its central origin. CONCLUSIONS: Two stress paradigms induced depressive-like behaviors that were sensitive to different antidepressant treatments. Biomarkers such as Aldolase C could help determine optimal antidepressant treatments for clinically depressed patients.


Subject(s)
Antidepressive Agents/pharmacology , Depressive Disorder/drug therapy , Fluoxetine/pharmacology , Fructose-Bisphosphate Aldolase/cerebrospinal fluid , Morpholines/pharmacology , Animals , Chronic Disease , Depressive Disorder/diagnosis , Depressive Disorder/metabolism , Disease Models, Animal , Fructose-Bisphosphate Aldolase/metabolism , Green Fluorescent Proteins/cerebrospinal fluid , Green Fluorescent Proteins/metabolism , Male , Rats, Sprague-Dawley , Reboxetine , Restraint, Physical , Selective Serotonin Reuptake Inhibitors/pharmacology , Serotonin and Noradrenaline Reuptake Inhibitors/pharmacology , Stress, Psychological
13.
PLoS One ; 10(2): e0117680, 2015.
Article in English | MEDLINE | ID: mdl-25679528

ABSTRACT

Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress.


Subject(s)
Cell Adhesion Molecules, Neuronal/genetics , DNA Methylation , Extracellular Matrix Proteins/genetics , Maternal Exposure , Mental Disorders/etiology , Nerve Tissue Proteins/genetics , Prenatal Exposure Delayed Effects , Promoter Regions, Genetic , Serine Endopeptidases/genetics , Stress, Physiological , Stress, Psychological , Animals , Animals, Newborn , Antigens, Nuclear/genetics , Antigens, Nuclear/metabolism , Behavior, Animal , Cell Adhesion Molecules, Neuronal/metabolism , Cerebral Cortex/metabolism , Cyclin-Dependent Kinase 5/metabolism , Disease Models, Animal , Extracellular Matrix Proteins/metabolism , Female , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Pregnancy , Rats , Reelin Protein , Serine Endopeptidases/metabolism , Signal Transduction
14.
FEM (Ed. impr.) ; 16(3): 167-179, sept. 2013. ilus, mapas
Article in Spanish | IBECS | ID: ibc-117411

ABSTRACT

Objetivo. Actualmente se acepta que el ambiente educacional influye en forma importante sobre las aptitudes, conocimientos, conducta, logros académicos y grado de satisfacción de los estudiantes. En este trabajo se analizan los cambios en la percepción del ambiente educacional por parte de los estudiantes de la Facultad de Medicina de la Universidad de Zaragoza, como consecuencia de la adaptación de su currículo a las indicaciones del Plan de Bolonia, que comenzó a aplicarse con el primer curso en el año 2009. Sujetos y métodos. Como instrumento de diagnóstico se aplicó la encuesta de medición de ambiente educacional, conocida como DREEM (Dundee Ready Education Environment Measure), a estudiantes provenientes del primer y tercer curso del año 2008 y a estudiantes del tercer curso del periodo 2011-2012. Como referencia o control, se tomaron las percepciones de los estudiantes de la Facultad de Medicina de la Universidad de Chile durante periodos equivalentes. Resultados. Con la implantación del Plan de Bolonia, la percepción del ambiente educativo de los estudiantes de la Universidad de Zaragoza ha disminuido significativamente en todos los dominios que forman parte de la encuesta (percepción de la enseñanza, percepción de los docentes, autopercepción académica, percepción del ambiente y autopercepción social). Conclusión. Los resultados aparentemente negativos de la aplicación del Plan de Bolonia en la Facultad de Medicina de la Universidad de Zaragoza podrían deberse a que el proceso no estaría siendo llevado de la forma mas adecuada por parte de las autoridades y los profesores (AU)


Aim. It is accepted that the educational environment affects aptitudes, knowledge, behaviors, academic achievements and satisfaction degrees among the students. In this study we analyzed the changes of education environment perception declared by the students of the Medical School from the University de Zaragoza, Spain, as a consequence of the curricular changes applied according to the rules established by the Bologna Plan, which begun to be applied in the first degree in 2009. Subjects and methods. The DREEM questionnaire (Dundee Ready Education Environment Measure) was used to evaluate the educational environment perception among the medical students belonging both to the first and third degree, 2008, and the third degree, 2011-2012. The perception of the medical students of the University of Chile, during similar periods, was taken as reference or control. Results. After the Bologna Plan application, the education environment perception has significantly decayed among the students of the University of Zaragoza in every of the DREEM questionnaire items (teaching perception, teachers perception, academic self-perception, environment perception and social self-perception). Conclusions. These apparently negative results of the Bologna Plan in the Zaragoza Medical School could be attributed to an inappropriate conduction by teachers and Faculty members (AU)


Subject(s)
Humans , Education, Medical, Undergraduate/trends , Models, Educational , Curriculum/trends , Students, Medical , Achievement , Educational Measurement
15.
Behav Brain Res ; 247: 92-100, 2013 Jun 15.
Article in English | MEDLINE | ID: mdl-23511254

ABSTRACT

Fluoxetine is currently being administered for long-term maintenance and for prophylactic reasons following the remission of depressive symptoms and several other psychiatric and neurological conditions. We have previously found that in naïve adult male rats, repetitive administration of fluoxetine induced maturation of telencephalic dendritic spines. This finding was associated with the presence of a higher proportion of GluA2- and GluN2A-containing glutamate receptors. To gain further insight into the possible consequences of such synaptic re-organization on learning and memory processes, we evaluated hippocampal- and non-hippocampal-dependent memories following administration of 0.7 mg/kg fluoxetine for four weeks. Standard behavioral tasks were used: the Morris Water Maze (MWM) and Object Location Memory (OLM) tasks to assess spatial memory and the Novel Object Recognition (NOR) task to assess recognition memory. We found that treated rats showed normal learning and short-term memory (1 h post-learning). However, either recent (24 h) or remote (17 days) memories were impaired depending upon the task. Interestingly, spatial memory impairment spontaneously reverted after 6 weeks of fluoxetine withdrawal.


Subject(s)
Fluoxetine/pharmacology , Hippocampus/drug effects , Maze Learning/drug effects , Memory, Long-Term/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Male , Rats , Rats, Sprague-Dawley , Recognition, Psychology/drug effects , Space Perception/drug effects
16.
Educ. méd. (Ed. impr.) ; 14(1): 27-34, mayo 2011. ilus, tab
Article in Spanish | IBECS | ID: ibc-92769

ABSTRACT

Objetivo. Evaluar y comparar la percepción que del ambiente educativo tienen los estudiantes de medicina de dos universidades iberoamericanas: Universidad de Chile (UCH) y Universidad Nacional de Cuyo (UNC), que desarrollan un currículo tradicional y un currículo basado en problemas, respectivamente. Sujetos y métodos. Participaron 465 estudiantes: 232 de la UCH y 233 de la UNC. La distribución fue de 84 y 70 estudiantes para el primer curso, 77 y 97 para el tercero, y 71 y 66 para el quinto, respectivamente. Se aplicó el cuestionario DREEM, que consiste en 50 ítems, agrupados en cinco dimensiones: percepción de la enseñanza, percepción de los profesores, autopercepción académica, percepción de la atmósfera educativa y autopercepción social. Resultados. Las puntuaciones totales fueron mayores en los tres cursos de la UNC. Resultaron similares en todos los cursos de ambas universidades, excepto en el quinto curso de la UCH. Respecto a la percepción acerca de los profesores, los estudiantes de quinto curso de la UCH mostraron las puntuaciones más bajas, mientras que los estudiantes del primer curso de la UNC tuvieron la mejor percepción. Resultados similares se obtuvieron en la autopercepción académica. La percepción del ambiente de aprendizaje fue mejor en la UNC y la autopercepción social tuvo puntuaciones similares en todos los cursos de ambas universidades. Conclusiones. Las diferencias observadas entre ambas universidades podrían atribuirse a sus diferentes currículos. El currículo basado en problemas parece ser mejor valorado que el tradicional. Nuestro estudio corrobora la eficacia del cuestionario DREEM para identificar fortalezas y debilidades del currículo y para evaluar la calidad de la enseñanza en facultades de medicina (AU)


Aim. To assess and compare the perception about the educational environment of medical students from two Latin-American universities, University of Chile (UCH) and National University of Cuyo (UNC), which develop a traditional curriculum and a problem based curriculum, respectively. Subjects and methods. A transversal study was performed in 465 students: 232 from the UCH and 233 from the UNC. The distribution was 84/70 for the first course, 77/97 for the third one and 71/66 for the fifth one, respectively. The DREEM questionnaire, which consists of 50 items, was applied. It covers 5 dimensions of the educational environment: perception about learning, perception about teachers, academic self-perception, perception about educational climate and social self-perception. Results. Total DREEM scores were significantly higher in the UNC. Scores were similar in all courses from both universities, with the exception of fifth course UCH. Regarding their perception about teachers, students of the fifth course UCH showed the lowest score, whereas students of the first course UNC had the best perception. Similar results were obtained for the academic auto-perception; while the perception of the learning environment obtained higher scores in the three courses from the UNC. Social auto-perception was similar in all courses tested in this study. Conclusions. Differences observed between both universities could be attributed to their different curricula. Problem based curriculum seems to be better appreciated than the traditional one. Our study corroborates the efficacy of the DREEM questionnaire to identify strengths and weaknesses of the curriculum and for the assessment of teaching quality in medical schools (AU)


Subject(s)
Humans , Male , Female , Adult , Educational Measurement/statistics & numerical data , Schools, Medical/statistics & numerical data , Students, Medical/statistics & numerical data , Social Perception , Personal Satisfaction , Problem-Based Learning/statistics & numerical data
17.
Behav Neurosci ; 124(5): 662-76, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20939666

ABSTRACT

3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a psychoactive drug structurally related to other phenylisopropylamines acting as stimulants or hallucinogens in humans. Although MDMA has a pharmacological identity of its own, the distinction of its acute effects from those of stimulants or even hallucinogens is controversial. In this work, dose-response curves (0.25, 0.5, 1, 3, 5, and 10 mg/kg) representing the acute in vivo effects of MDMA were compared with those of a structurally related stimulant (methamphetamine, MA) and a hallucinogenic analogue (2,5-dimethoxy-4-iodoamphetamine, DOI) in a set of behavioral protocols in rats, including spontaneous psychomotor activity, anxiolytic/anxiogenic-like effects and active avoidance conditioning responses. The behavioral profiles obtained allowed us to differentiate among racemic MDMA, MA, and DOI at different dose ranges. In addition, the evaluation of four MDMA analogues (1, 5, and 10 mg/kg) comprising two well-known MDMA analogues (MDA [3,4-methylenedioxyamphetamine] and MDE (N-ethyl-MDA, believed to substitute for MDMA) and two other structural analogues (MDOH [N-hydroxy-MDA] and MMDA-2 [2-methoxy-4,5-methylenedioxyamphetamine]) showed that none of these exactly resembles MDMA in their pharmacological profiles, highlighting the unique character of this prototypical entactogen. In fact, their effects exhibited similarities with the behavioral profiles of either MA or DOI, as well as novel profiles in specific behavioral paradigms.


Subject(s)
Amphetamines/pharmacology , Behavior, Animal/drug effects , Methamphetamine/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/analogs & derivatives , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Animals , Avoidance Learning/drug effects , Central Nervous System Stimulants/pharmacology , Dose-Response Relationship, Drug , Hallucinogens/pharmacology , Male , Maze Learning/drug effects , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley
18.
Behav Pharmacol ; 20(3): 273-85, 2009 May.
Article in English | MEDLINE | ID: mdl-19424057

ABSTRACT

Extracellular signal-regulated kinases (ERKs) are widely implicated in multiple physiological processes. Although ERK1/2 has been proposed as a common mediator of antidepressant action in naive rodents, it remains to be determined whether the ERK1/2 pathway plays a role in depressive disorder. Here, we investigated whether chronic restraint stress (14 days) and antidepressant treatment [desipramine (DMI), 10 mg/kg intraperitoneally] induce changes in animal behavior and hippocampal levels of phospho-ERK1/2 and its substrate phospho-cAMP response element-binding protein (CREB). The results indicated that stress-induced depressive-like behaviors were correlated with an increase in P-ERK1/2 and P-CREB in the hippocampus evaluated by immunoblot analysis. As an indication of CREB activity, we evaluated changes in mRNA levels of its target genes. Brain-derived neurotrophic factor (BDNF) mRNA was reduced by stress, an effect prevented by DMI only in the CA3 area of hippocampus. Bcl-2 mRNA was reduced in all hippocampal regions by stress, an effect independent of DMI treatment. However, immunoblot from hippocampal extracts revealed that stress increased BCL-2 levels, an effect prevented by chronic DMI. These results suggest that ERKs and BDNF may be altered in depressive disorder, modifications that are sensitive to DMI action. In contrast, the stress-induced increase in BCL-2 may correspond to a neuroprotective response.


Subject(s)
Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Desipramine/pharmacology , Hippocampus/metabolism , Neuroprotective Agents/pharmacology , Stress, Psychological/prevention & control , Animals , Antidepressive Agents/therapeutic use , Behavior, Animal , Biomarkers/metabolism , Brain-Derived Neurotrophic Factor/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Desipramine/therapeutic use , Extracellular Signal-Regulated MAP Kinases/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Hippocampus/drug effects , Injections, Intraperitoneal , Male , Neuroprotective Agents/therapeutic use , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Stress, Psychological/metabolism , Stress, Psychological/psychology
19.
Behav Brain Res ; 203(1): 88-96, 2009 Oct 12.
Article in English | MEDLINE | ID: mdl-19397934

ABSTRACT

Chronic stress induces dendritic atrophy in the inferior colliculus (IC, auditory mesencephalon) and impairs auditory avoidance conditioning. The aim of this study was to determine in Golgi preparations and in cued fear conditioning whether stress affects other auditory components, like the thalamic medial geniculate nucleus (MG) or the posterior thalamic nucleus (PO), in Sprague-Dawley rats. Chronic restraint stress produced a significant dendritic atrophy in the MG (stress: 407+/-55 microm; control: 808+/-120 microm; p<0.01) but did not affect auditory fear conditioning. The last result was in apparent contrast with the fact that stress impairs both the acquisition of auditory avoidance conditioned responses and the dendritic structure in two major nuclei of the auditory system. In order to analyze this disagreement, we investigated whether the stress-related freezing to tone occurring in the fear conditioning protocol corresponded to a conditioned or an unconditioned fear response, using changes in tone instead of light throughout conditioning trials. Chronic stress significantly enhanced visual fear conditioning in stressed animals compared to controls (stress: 58.9+/-8.42%, control: 23.31+/-8.01%; p<0.05), but this fear enhancement was related to unconditioned fear. Conversely, chronic stress did not affect the morphology of the PO (subserving both auditory and somatosensory information) or the corresponding auditory and somatosensory unconditioned responses (acoustic startle response and escape behavior). Our results suggest that the auditory conditioned stimulus can be processed in part independently of the IC and MG in the stressed animals, and sent to the amygdala via the PO inducing unconditioned fear. Comparable alterations could be produced in major depression.


Subject(s)
Auditory Perception/physiology , Conditioning, Classical/physiology , Dendrites/physiology , Geniculate Bodies/physiopathology , Neurons/physiology , Stress, Psychological/physiopathology , Acoustic Stimulation , Animals , Escape Reaction , Fear , Freezing Reaction, Cataleptic , Geniculate Bodies/cytology , Male , Neurons/cytology , Photic Stimulation , Posterior Thalamic Nuclei/cytology , Posterior Thalamic Nuclei/physiopathology , Random Allocation , Rats , Rats, Sprague-Dawley , Reflex, Startle , Restraint, Physical , Visual Perception/physiology
20.
Chem Res Toxicol ; 21(6): 1180-5, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18500786

ABSTRACT

The dependence of copper neurotoxicity on DT-diaphorase inhibition was suggested from results obtained from a cell line derived from substantia nigra. Therefore, the aim of this study was to evaluate whether CuSO4 neurotoxicity in vivo, which was evaluated by determining the contralateral rotation and loss of tyrosine hydroxylase immunostaining, was dependent on DT-diaphorase inhibition by dicoumarol. Animals unilaterally and intranigrally injected with 0.25 nmol of CuSO4 and 2 nmol of dicoumarol presented a significant and characteristic contralateral rotational behavior ( P < 0.01) when they were systemically stimulated with apomorphine (0.5 mg/kg s.c.), similar to that observed in rats injected unilaterally with 6-hydroxydopamine as a positive control. The behavioral effects correlated with the lost of tyrosine hydroxylase-positive staining, since animals unilaterally and intranigrally injected with 0.25 nmol of CuSO4 together with 2 nmol of dicoumarol exhibited extensive loss of tyrosine hydroxylase-positive fiber density in the striatum ( P < 0.01) and cell loss in the substantia nigra ( P < 0.01). Our results support the idea that CuSO4 neurotoxicity is dependent upon DT-diaphorase inhibition.


Subject(s)
Copper/toxicity , NAD(P)H Dehydrogenase (Quinone)/antagonists & inhibitors , Neostriatum/drug effects , Neostriatum/enzymology , Nervous System Diseases/enzymology , Substantia Nigra/drug effects , Substantia Nigra/enzymology , Animals , Behavior, Animal/drug effects , Male , NAD(P)H Dehydrogenase (Quinone)/metabolism , Nervous System Diseases/pathology , Rats , Rats, Sprague-Dawley , Tyrosine 3-Monooxygenase/metabolism
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