Hipotiroidismo en el adulto: su influencia en la estructura y función de la formación hipocampal de la rata

Trabajo realizado en colaboración con el Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC-UAMTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica.Fecha de lectura: 24 de Julio de 2009Bibliografía h. 92-10

Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment

Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis

Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rodents. Bulk tissue and single-nucleus expression profiling disclose sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage channels, synaptic signaling, and cell adhesion are deregulated differently by epilepsy across sublayers, whereas neurodegenerative signatures primarily involve superficial cells. Pseudotime analysis of gene expression in single nuclei and in situ validation reveal separated trajectories from health to epilepsy across cell types and identify a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate that sublayer- and cell-type-specific changes associated with selective CA1 neuronal damage contribute to progression of hippocampal sclerosis.This work was supported by grants from MICINN (RTI2018-098581-B-I00 to L.M.P.), Fundación Tatiana Pérez de Guzman el Bueno, and the SynCogDis Network (SAF2014-52624-REDT and SAF2017- 90664-REDT to L.M.P. and A. Bayes). Collaboration between L.M.d.l.P. and Y.H. was supported by Human Frontiers Science Program (HFSP) grant RGP0022/2013. J.P.L.-A. was supported by grants from MICIU co-financed by ERDF (RYC-2015-18056 and RTI2018-102260-B-I00) and Severo Ochoa grant SEV-2017-0723. R.R.-V. and A. Bayes were supported by MINECO BFU2015-69717-P and RTI2018-097037-B-100 and a Marie Curie career integration grant (ref. 304111). A.V.M. was supported by MICINN (SAF2017- 85717-R) and Fundación Alicia Koplowitz. A. Barco was supported by grants SAF2017-87928-R from MICINN co-financed by ERDF and RGP0039/2017 from the Human Frontiers Science Program Organization. The Instituto de Neurociencias is a ‘‘Centre of Excellence Severo Ochoa.’’ D.G.-D. and C.M.N. hold PhD fellowships from MICINN (BES-2013-064171 and BES2016-076281, respectively).Peer reviewe

Temas Socio-Jurídicos. Volumen 15 No. 33 Diciembre de 1997

La edición número 33 de la revista temas socio-jurídicos pone a consideración de sus lectores, los trabajos elaborados por docentes y estudiantes de la Facultad de Derecho de la Universidad Autónoma de Bucaramanga, en éste, su vigésimoquinto año de funcionamiento.The 33rd edition of the socio-legal issues magazine presents to its readers the works prepared by teachers and students of the Faculty of Law of the Autonomous University of Bucaramanga, in its twenty-fifth year of operation

Generations UNAB No.4

Esta cuarta edición de la revista Generaciones UNAB, gira en torno a la celebración de los 40 años de inicio de labores de la Facultad de Derecho, cuyo primeros 25 graduados obtuvieron su título en 1978; así como a la celebración de los primeros 30 años de inicio de labores de la Facultad de Comunicación Social que graduó a sus primeros 17 estudiantes en 1987. Hoy, cuatro y tres décadas después del inicio de labores respectivamente, y atendiendo al compromiso institucional con la región, ña Universidad ha permitido que Santander, Colombia y el mundo cuenten con 3.104 abogados y 1.647 comunicadores sociales que se destacan por su compromiso con la sociedad, su trabajo en equipo, ética y valores en el ejercicio profesional.Editorial; Por Marcela Peralta Bautista…03 Columnista invitado, Facultades bien dirigidas; Por Alfonso Gómez Gómez…06 40 años de la Facultad de Derecho…08 Cuatro décadas formando futuro; Por José Manuel Arias Carrizosa…09 Una facultad de libertadores; Por Jaime Gutiérrez Rivero…10 Defendiendo la libertad del conocimiento; Por Sergio Rangel Consuegra…11 La cara humana del derecho; Por Jorge González Aranda…13 La decanatura marcó mi vida; Por Gabriel Burgos Mantilla…14 La unión hace la fuerza; Por Jorge Castillo Rugeles…16 Mis estudiantes son lo más importante; Por Rodolfo Mantilla Jácome…18 La hermenéutica jurídica como sello diferenciador; Por Juan Carlos Acuña Gutiérrez...20 Equipo de trabajo y apoyo directivo; Por Jorge Eduardo Lamo Gómez…22 30 años de la Facultad de Comunicación Social…25 Haciendo el sueño realidad; Por Carlos H. Gómez…26 Un compromiso de vida; Por Maria Isabel León Carreño…28 Construir debatiendo; Por Rodrigo Velasco Ortiz…30 La importancia de potenciar capacidades; Por Luz Amalia Camacho Velásquez...32 Una propuesta académica única; Por Iván Darío Montoya Osorio…34 Graduados Destacando…37 Docente en la Facultad de Derecho UNAB…38 Comunicación Social-Periodista de la UNAB; Por Sonia Díaz…39 Emprendedores UNAB “Apps.com”; Por Marcela Peralta Bautista…40 Instigación “Trata de personas”; Por Lya Fernández de Mantilla, Johana Marcela Reyes…42 Encuentros…45This fourth edition of the magazine Generaciones UNAB, revolves around the celebration of 40 years of beginning of work of the Faculty of Law, whose first 25 graduates obtained their degree in 1978; as well as the celebration of the first 30 years of beginning of work of the Faculty of Social Communication that graduated its first 17 students in 1987. Today, four and three decades after the start of work respectively, and in response to the institutional commitment to the region, ña University has allowed Santander, Colombia and the world to have 3,104 lawyers and 1,647 social communicators who stand out for their commitment to society , their teamwork, ethics and values ​​in professional practice

Effects of thyroid hormone replacement on associative learning and hippocampal synaptic plasticity in adult hypothyroid rats

Activity-dependent changes taking place at the hippocampal perforant pathway–dentate gyrus synapse during classical eyeblink conditioning were recorded in adult thyroidectomized (hypothyroid) and control (euthyroid) rats, and in animals treated with thyroid hormones 20 days after thyroidectomy (recovery rats). The aim was to determine the contribution of thyroid hormones and the consequences of adult-onset hypothyroidism to both associative learning and the physiological potentiation of hippocampal synapses during the actual learning process in alert behaving animals. Control and recovery rats presented similar learning curves, whereas hypothyroid animals presented lower values. A single pulse presented to the perforant pathway during the conditioned–unconditioned inter-stimulus interval evoked a monosynaptic field excitatory postsynaptic potential in dentate granule cells (whose slope was linearly related to the rate of acquisition in the control group), but not in hypothyroid and recovery animals. Input–output relationships and long-term potentiation evoked by train stimulation of the perforant pathway were significantly depressed in hypothyroid animals. Thyroid hormone treatment failed to normalize these two neurophysiological abnormalities observed in hypothyroid animals. In contrast, paired-pulse facilitation was not affected by thyroidectomy. The results indicate that thyroid hormone treatment after a short period of adult hypothyroidism helps to restore some hippocampally dependent functions, such as classical conditioning, but not other hippocampal properties, such as the synaptic plasticity evoked during associative learning and during experimentally induced long-term potentiation. The present results have important clinical implications for the handling of patients with adult-onset thyroid diseases.This work was supported by the Spanish Ministry of Science and Innovation (BFU2005-01024, BFU2005-02512, BFU2004-05944, and BFU2007-62979) and by the Comunidad Autónoma de Madrid ⁄ CSIC, Spain (CCG07-CSIC_SAL-1845).Peer Reviewe

Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala

Resumen del póster presentado a la Seventh Cajal Winter Conference on Synaptic mechanisms, celebrada en Benasque, Huesca (España) del 20 al 24 de marzo de 2011.Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.Peer Reviewe

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

11 pages, 5 figures.-- PMID: 16446739.Hormonal imbalances are involved in many of the age-related pathologies, as neurodegenerative and psychiatric diseases. Specifically, thyroid state alterations in the adult are related to psychological changes and mood disorders as depression. The dentate gyrus of the hippocampal formation undergoes neurogenesis in adult mammals including humans. Recent evidence suggests that depressive disorders and their treatment are tightly related to the number of newly born neurons in the dentate gyrus.We have studied the effect of thyroid hormones (TH) on hippocampal neurogenesis in adult rats in vivo. A short period of adult-onset hypothyroidism impaired normal neurogenesis in the subgranular zone of the dentate gyrus with a 30% reduction in the number of proliferating cells. Hypothyroidism also reduced the number of newborn neuroblasts and immature neurons (doublecortin (DCX) immunopositive cells) which had a severely hypoplastic dendritic arborization. To correlate these changes with hippocampal function, we subjected the rats to the forced swimming and novel object recognition tests. Hypothyroid rats showed normal memory in object recognition, but displayed abnormal behavior in the forced swimming test, indicating a depressive-like disorder. Chronic treatment of hypothyroid rats with TH not only normalized the abnormal behavior but also restored the number of proliferative and DCX-positive cells, and induced growth of their dendritic trees. Therefore, hypothyroidism induced a reversible depressive-like disorder, which correlated to changes in neurogenesis.Our results indicate that TH are essential for adult hippocampal neurogenesis and suggest that mood disorders related to adult-onset hypothyroidism in humans could be due, in part, to impaired neurogenesis.This work was supported by Grants BFI2001-2412 and BFU2004-05944 (A.G.-F), BFI2002-00489 (J.B.), BFI2003-07524 (C.V.) from the Ministry of Science and Technology and FIS, Instituto de Salud Carlos III, Red de Centros RCMN (C03/08). A.M.-P. and I.F.-L. are recipient of a fellowship and A.G.-F. and C.V. of a contract from the Ramón y Cajal Program, all of the Ministry of Science and Technology, Spain.Peer reviewe

In vivo proton magnetic resonance spectroscopy regional metabolic profiles: differences among hippocampal formation, prefrontal cortex and cerebellum in adult rats using a machine learning approach

Resumen del póster presentado al Neuroscience celebrado en Nueva Orleans (USA) del 13 al 17 de octubre de 2012.1H-Magnetic resonance spectroscopy (1H-MRS) is a non-invasive technology that provides information about several metabolite levels among multiple brain regions. This technology is widely used in preclinical and neuroscience research and in diagnosis in neurological practice. Although CNS is highly heterogeneous, few studies have been focused on interregional differences in 1H-MRS metabolic profiles and fewer, if any, have used multivariate approaches. Our aim is the development of a methodology to compare 1H-MRS metabolic profiles in order to improve the 1H-MRS result interpretation. In vivo spectra were acquired with a 7T PharmaScan® System (voxel size 27 mm3 and PRESS sequence, TE=35 ms) and fitted with LCModel. To avoid variance in signals, metabolite levels were normalized to NAA (N-Acetyl Aspartate). Four ratios to NAA were obtained: NAA+NAAG (NAA+N-Acetyl Aspartyl Glutamate), Cr+PCr (total Creatine), GPC+PCh (total Choline) and Glx (Glutamate+Glutamine) in hippocampal formation, prefrontal cortex and cerebellum from adult Wistar rats, aged 80, 105 and 130 days (n=8 each condition). Linear discriminant analysis (LDA), random forests (RF) and supervised neural networks (SNN) were used to classify brain regions according to age and NAA ratios. Cohen¿s kappa and the area under the receiver operating characteristic curve (AUC) were respectively calculated to measure global performance of each approach and each region in particular. Confidence intervals were calculated by bootstrapping. To measure discriminating importance of each dependent variable, the correlations among them and linear discriminant functions in LDA and the mean decrease in accuracy in RF were used. LDA, RF and SNN were able to discriminate among regions (Table 1). LDA showed the best global fitting. Compared to the others, the cerebellum metabolic profile was the most different. Cr+PCr and Glx were important in separating cerebellum and hippocampal formation respectively. Age was not an important factor in the models. This study provides a valid methodology to explore 1H-MRS interregional metabolic profiles detecting significant regional differences that are important in 1H-MRS result interpretation. This fact should be considered in clinical context.Peer Reviewe