Editorial: Neurodegenerative Diseases: Looking Beyond the Boundaries of the Brain

Neurodegenerative Diseases: Looking Beyond the Boundaries of the Brai

LA DISLEXIA COMO MANIFESTACIÓN DE NEURODIVERSIDAD

La habilidad lectora está representada por una curva de distribución normal en la que el fenotipo denominado disléxico constituye aproximadamente el 17%. Esta distribución y frecuencia hacen de este fenotipo una expresión alternativa de la normalidad lectora en el ser humano. En este trabajo se propone un modelo que mira a la dislexia como una manifestación de neurodiversidad, superando las ideas que la presumen como una neuropatología. En él se sugiere que las variantes disléxicas son alternativas fenotípicas que permiten a los individuos desarrollar habilidades cognitivas novedosas y adaptativas. Para este fin, se analizó el marco conceptual y experimental de 143 artículos científicos obtenidos de las bases de datos ScienceDirect, NCBI y PubMed, seleccionados bajo los términos de búsqueda “dislexia” y “lectura”, relacionados con su neurobiología, diagnóstico, características y neurodiversidad. La inclusión adicional de datos neurofisiológicos y neuroanatómicos, representados por modelos a lo largo del trabajo, permitió ilustrar la diversidad de las organizaciones cerebrales que ratifican la idea de que los “cerebros disléxicos” no representan un rasgo fenotípico inadaptado, sino más bien un arreglo de organizaciones cerebrales que proporcionan posibilidades cognitivas diversas. En consecuencia, se construyó un modelo neurobiológico teórico para lectura y dislexia que procura predecir las múltiples posibilidades de procesamiento de la información para ambos fenotipos. Esta teorización condujo a proponer un nuevo concepto para referirse a las variantes “disléxicas” del fenotipo humano, la holodisnomia, término que aspira a sustituir el término dislexia y que atiende a la capacidad de los individuos que lo exhiben de procesar la información de manera global (holo-), así como desarrollar una estructura de pensamiento que diverge positivamente de la norma (-disnomia)

Modulatory Role of Sensory Innervation on Hair Follicle Stem Cell Progeny during Wound Healing of the Rat Skin

BACKGROUND: The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. METHODOLOGY/PRINCIPAL FINDINGS: We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles. CONCLUSIONS/SIGNIFICANCE: Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing

Supernumerary Formation of Olfactory Glomeruli Induced by Chronic Odorant Exposure: A Constructivist Expression of Neural Plasticity

It is accepted that sensory experience instructs the remodelling of neuronal circuits during postnatal development, after their specification has occurred. The story is less clear with regard to the role of experience during the initial formation of neuronal circuits, whether prenatal or postnatal, since this process is now supposed to be primarily influenced by genetic determinants and spontaneous neuronal firing. Here we evaluated this last issue by examining the effect that postnatal chronic exposure to cognate odorants has on the formation of I7 and M72 glomeruli, iterated olfactory circuits that are formed before and after birth, respectively. We took advantage of double knock-in mice whose I7 and M72 primary afferents express green fluorescent protein and β-galactosidase, correspondingly. Our results revealed that postnatal odorant chronic exposure led to the formation of permanent supernumerary I7 and M72 glomeruli in a dose and time dependent manner. Glomeruli in exposed mice were formed within the same regions of olfactory bulb and occupy small space volumes compared to the corresponding single circuits in non-exposed mice. We suggest that local reorganization of the primary afferents could participate in the process of formation of supernumerary glomeruli. Overall, our results support that sensory experience indeed instructs the permanent formation of specific glomeruli in the mouse olfactory bulb by means of constructivist processes

Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats

Tramadol is an effective pharmacological intervention in human premature ejaculation (PE). To investigate whether the inhibitory action of tramadol is primarily caused by its selective serotonin reuptake inhibitory (SSRI) effects we tested the dose–response effects of tramadol on sexual behavior in serotonin transporter wild type (SERT+/+), heterozygous (SERT+/-), and knockout (SERT-/-) rats. To investigate whether other mechanisms contribute to the inhibitory effects, WAY100,635, a 5-HT1A receptor antagonist and naloxone, a μ-opioid receptor antagonist, were tested on sexual behavior together with tramadol. Tramadol dose-dependently decreases sexual activity in all genotypes. In all studies, SERT+/- rats did not respond differently from SERT+/+ rats. WAY100,635 did not affect sexual activity in SERT+/+, but dose-dependently reduced sexual activity in SERT-/- rats. WAY100,635 (0.3 mg/kg) combined with tramadol (20 mg/kg) significantly reduced sexual activity in SERT+/+ and even stronger in SERT-/- rats. Naloxone did not affect sexual behavior consistently in SERT+/+ rats, while in SERT-/- rats all doses reduced ejaculation frequency mildly. Combining naloxone (20 mg/kg) and tramadol (20 mg/kg) decreased ejaculation frequencies in both genotypes. Interestingly, combining tramadol (20 mg/kg), WAY100,635 (0.3 mg/kg) and naloxone (20 mg/kg) led to complete elimination of all sexual activity in both SERT+/+ and SERT-/- rats. These findings suggest that the inhibitory effects of tramadol on male sexual behavior in SERT+/+ rats is mainly, if not exclusively, due to SERT inhibition, with an important role for 5-HT1A receptors, although influence of other systems (e.g., noradrenergic) cannot be excluded. As SSRIs exert their sexual inhibition after chronic administration, tramadol may be therapeutically attractive as “on demand” therapy for PE

Treating horse chronic laminitis with allogeneic bone marrow mesenchymal stem cells

La laminitis crónica es una condición incapacitante que afecta el corion laminar de los cascos del caballo. Por lo general, se desarrolla como una lesión colateral de numerosas enfermedades sistémicas primarias. Se cree que el evento fisiopatológico crítico que hace que un casco sea vuelva laminítico es la pérdida de células madre mesenquimales. Esta pérdida perjudica en gran medida la capacidad del corion laminar para regenerarse. Aunque el trabajo previo proporciona credibilidad a esta noción, quedan cuestiones sin resolver que deben abordarse antes de aceptarla como un hecho bien fundado. Aquí, se reexaminó el principio central del modelo fisiopatológico de la laminitis mediante la infusión de células madre mesenquimales alogénicas derivadas de la médula ósea (CMM-AMO), a través de la vena palmar digital, en los cascos de los caballos afectados por laminitis crónica. Los caballos fueron monitoreados clínicamente durante 6 meses, evaluándolos mensualmente utilizando la escala de Obel-Glasgow de cojera modificada y la termografía de cascos. Se tomaron venogramas y biopsias laminares al principio y al final del período de estudio para reunir evidencia sobre la remodelación vascular y la regeneración del corion laminar. Los resultados mostraron que la infusión de CMM-AMO promueve la remodelación vascular y la regeneración del corion laminar, lo que respalda aún más que la pérdida de células madre es el evento crítico que conduce a la laminitis crónica. Este trabajo también demostró que la infusión de CMM-AMO es segura ya que los caballos tratados no desarrollaron manifestaciones clínicas negativas locales o sistémicas en sintonía con reacciones de rechazo, al menos durante el período de 6 meses en que se les dio seguimiento y bajo el esquema terapéutico propuesto.Chronic laminitis is a disabling condition that affects the laminar corium of the horse’s hooves. Commonly, it develops as a collateral injury of numerous primary systemic diseases. It is believed that the critical physiopathological event that renders a hoof laminitic is the loss of mesenchymal stem cells. This loss greatly impairs the ability of the laminar corium to regenerate. Although previous work provides credibility to this notion, there remain unsettled issues that must be addressed before accepting it as a well-founded fact. Here, it was reexamined the central tenet of the physiopathological model of laminitis by infusing allogeneic bone marrow-derived mesenchymal stem cells (ABM-MSCs), through the digital palmar vein, into the hooves of horses afflicted by chronic laminitis. Horses were clinically monitored during 6 mo by evaluating them monthly using the lameness-modified Obel-Glasgow’s scale and hooves thermography. Venograms and lamellar biopsies were taken at the beginning and at the end of the study period to gathered evidence on vascular remodeling and laminar corium regeneration. The results showed that ABM-MSCs infusion promotes vascular remodeling and laminar corium regeneration, further supporting that the loss of stem cells is the critical event leading to chronic laminitis. This work also demonstrated that the infusion of ABM-MSCs is safe since the treated horses did not develop local or systemic, negative clinical manifestations attuned with rejection reactions, at least during the 6-mo period they were follow up and under the therapeutic scheme proposed

Insulin-like growth factor 1 (IGF-1) concentrations in synovial fluid of sound and osteoarthritic horses, and its correlation with proinflammatory cytokines IL-6 and TNF

El factor de crecimiento similar a la insulina I (IGF-1) es el factor de crecimiento conocido más importante para la reparación del cartílago en caballos. Promueve la mitosis de los condrocitos, la expresión de colágeno II y la producción de matriz extracelular. La osteoartritis (OA) es la condición musculoesquelética más común que causa cojera y bajo rendimiento en caballos deportivos. Se evaluó clínica y radiográficamente un total de 11 caballos cojos, y se confirmó que todos sufrían una cojera metacarpofalángica frontal mediante una prueba de flexión positiva, un bloqueo nervioso en 4 puntos bajos y un bloqueo intraarticular. La proteína total, IGF-1, IL-6 y TNFα se determinaron por ELISA, lo que demostró cambios y diferentes correlaciones entre la condición clínica, los cambios radiográficos y el grado de inflamación. Todos los caballos con dolor asociado a las articulaciones y, por lo tanto, asociado a la cojera, mostraron un aumento significativo de la proteína total (P<0.0001) y la concentración de IGF-1 (P<0.05). Las concentraciones de IL-6 y TNFα entre los controles y los caballos cojos mostraron diferencias significativas (P<0.01 y P<0.001 respectivamente). Los caballos con menos cambios radiográficos mostraron la mayor expresión de IGF-1 en el líquido sinovial, y los caballos con condiciones de OA más crónicas tuvieron niveles de expresión de IGF-1 muy similares a los de las articulaciones de control. En todas las articulaciones cojas, se identificó por medio de Western blot una isoforma de IGF-1 más ligera (~ 7.5 kDa) que estaba relacionada con la inflamación y es el peso molecular del péptido maduro, y todas las articulaciones de control expresaron una isoforma más pesada (~ 12 kDa). Este hallazgo podría conducir a una nueva investigación para secuenciar y apuntar a la isoforma que no se expresa durante un proceso inflamatorio dentro de una articulación, y para tener una mejor comprensión de su papel en la articulación del caballo.Insulin-like growth factor I (IGF-1) is the most important known growth factor for cartilage repair in horses. It promotes mitosis of chondrocytes, collagen II expression, and extra cellular matrix production. Osteoarthritis (OA) is the most common musculoskeletal condition that causes lameness and poor performance in sport horses. A total of 11 lame horses were clinically and radiographically evaluated, and all were confirmed to suffer a front metacarpophalangeal lameness by a positive flexion test, a low-4-point nerve block and an intraarticular block. Total protein, IGF-1, IL-6 and TNFa were determined by ELISA, demonstrating changes and different correlations between clinical condition, radiographic changes and degree of inflammation. All horses with joint associated pain and therefore associated lameness, demonstrated a significant increase of total protein (P<0.0001) and IGF-1 concentration (P<0.05). Concentrations of IL-6 and TNFa between controls and lame horses demonstrated significant differences (P<0.01 and P<0.001 respectively). Horses with less radiographic changes, demonstrated the highest IGF-1 expression in synovial fluid, and horses with more chronic OA conditions had very similar IGF-1 expression levels than control joints. In all lame joints, it was identified by Western blot a lighter isoform of IGF-1 (~7.5 kDa) which was inflammation related and it is the molecular weight of the mature peptide, and all control joints expressed a heavier isoform (~12 kDa). This finding could lead to new research for sequencing and targeting the isoform which is not expressed during an inflammatory process within a joint, and to have a better understanding of its role in the horse’s joint

Restructuring of Pancreatic Islets and Insulin Secretion in a Postnatal Critical Window

Function and structure of adult pancreatic islets are determined by early postnatal development, which in rats corresponds to the first month of life. We analyzed changes in blood glucose and hormones during this stage and their association with morphological and functional changes of alpha and beta cell populations during this period. At day 20 (d20), insulin and glucose plasma levels were two- and six-fold higher, respectively, as compared to d6. Interestingly, this period is characterized by physiological hyperglycemia and hyperinsulinemia, where peripheral insulin resistance and a high plasmatic concentration of glucagon are also observed. These functional changes were paralleled by reorganization of islet structure, cell mass and aggregate size of alpha and beta cells. Cultured beta cells from d20 secreted the same amount of insulin in 15.6 mM than in 5.6 mM glucose (basal conditions), and were characterized by a high basal insulin secretion. However, beta cells from d28 were already glucose sensitive. Understanding and establishing morphophysiological relationships in the developing endocrine pancreas may explain how events in early life are important in determining adult islet physiology and metabolism

Identificación y caracterización de grupos biológicos (comunidades hidrobiológicas, macroinvertebrados, plantas acuáticas, peces, anfibios, plantas terrestres, reptiles, aves y mamíferos), en el complejo ventana piloto de humedales de Paz de Ariporo-Hato Corozal

Este documento es resultado de la ejecución del Contrato 14-13-014-237PS entre el Instituto Humboldt y la Fundación Omacha, firmado en el marco del Convenio 005 (13-014) entre el Instituto Humboldt y el Fondo Adaptación. Contiene la propuesta para la identificación del límite funcional de la ventana piloto de humedales Paz de Ariporo-Hato Corozal, donde se estudiaron en los principales tipos de humedales naturales asociados a las cuencas de los ríos Ariporo y Chire (caños, cañadas, bosques de rebalse, matorrales inundables y cuerpos lénticos como esteros, lagunas de rebalse, bajos y madreviejas) la composición, estructura y uso del hábitat de los grupos biológicos asociados, tanto a los cuerpos de aguas como en las zonas transicionales acuático terrestres.BogotáSubdirección de Servicios Científicos y Proyectos Especiale