9 research outputs found
Mecanismos involucrados en la promoci贸n de crecimiento axonal por la glia envolvente del bulbo olfatorio
Neuroplasticity promoted by olfactory ensheathing cells depends on the expression of several molecules during development, adult life and lesion repair. Diverse molecules including neurotrophins and associated receptors, cellular adhesion molecules, extracellular matrix molecules and molecules associated with myelinization are present in the olfactory system during development. Furthermore, their expression continues into adult life and appears to be associated with cellular replacement and the high degree of plasticity of the olfactory system. Olfactory ensheating cell migration, accompanying growing axons, is observed during development, and trasplanted glia cells enable the navigation of regenerating sensory sprouts through inhibitory gliotic tissue formed after lesion of the central nervous system. The purpose of this review is to provide an insight into the neuroregenerative mechanisms and growth promoting properties of these cells.La actividad que promueve el crecimiento de axones por la glia envolvente (GE) del bulbo olfatorio depende de la expresi贸n de diversas mol茅culas durante el desarrollo, la vida adulta y la reparaci贸n de lesiones nerviosas. Diversas mol茅culas tales como las neurotrofinas y sus receptores, los factores de crecimiento, las mol茅culas de adhesi贸n celular, las mol茅culas de matriz extracelular y las mol茅culas asociadas con la mielinizaci贸n son producidas por la glia del sistema olfatorio durante el desarrollo. Su expresi贸n sostenida durante la vida adulta parece estar asociada con el reemplazo celular y la alta plasticidad de este sistema. A su vez, su expresi贸n se involucra en procesos de reparaci贸n de lesiones mediados por trasplantes de glia. La migraci贸n de la GE, que acompa帽a axones en crecimiento, se observa durante el desarrollo y en procesos de regeneraci贸n luego de una lesi贸n. Los trasplantes de,GE permiten la navegaci贸n de brotes regenerantes a trav茅s del tejido gli贸tico inhibidor formado luego de una lesi贸n del sistema nervioso central. El prop贸sito de esta revisi贸n es profundizar en los mecanismos de actividad promotora de crecimiento axonal
Reparaci贸n de lesiones por avulsi贸n del plexo braquial mediante el trasplante de Gl铆a envolvente del bulbo olfatorio
Tesis doctoral in茅dita le铆da en la Universidad Aut贸noma de Madrid. Facultad de Ciencias. Departamento de Biolog铆a Molecular. Fecha de lectura:31-01-200
Hippocampal CCR5/RANTES elevations in a rodent model of post-traumatic stress disorder: Maraviroc (a CCR5 antagonist) increases corticosterone levels and enhances fear memory consolidation
Background: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated. Aim: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats. Results: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training. Conclusion. Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session
Degeneraci贸n de los terminales aferentes primarios de rata luego de lesi贸n extensa por avulsi贸n del plexo braquial
Important breakthroughs in the understanding regeneration failure in an injured CNS have been made by studies of primary afferent neurons. Dorsal rhizotomy has provided an experimental model of brachial plexus (BP) avulsion. This is an injury in which the central branches of primary afferents are disrupted at their point of entry into the spinal cord, bringing motor and sensory dysfunction to the upper limbs. In the present work, the central axonal organization of primary afferents was examined in control (without lesion) adult Wistar rats and in rats subjected to a C3-T3 rhizotomy. Specific sensory axon subtypes were recognized by application of antibodies to the calcitonin gene-related peptide (CGRP), the P2X3 purinoreceptor, the low-affinity p75-neurotrophin receptor and the retrograde tracer cholera toxin subunit b (TCb ). Other subtypes weres labeled with the lectin Griffonia simplicifolia IB4. Using immunohistochemistry and high resolution light microscopy, brachial plexus rhizotomy in adult rats has proven a reliable model for several neural deficits in humans. This lesion produced different degrees of terminal degeneration in the several types of primary afferents which define sub-populations of sensitive neurons. Between the C6 and C8 levels of the spinal cord,,deafferentation was partial for peptidergic GCRP-positive fibers, in contrast with elimination of non peptidergic and myelinated fibers. Dorsal rhizotomy has provided an adequate experimental model to study sensory alterations such as acute pain and allodynia as well as factors that affect regeneration into the CNS., Therefore, the differential deafferentation response must be considered inr the evaluation of therapies for nociception (pain) and regeneration for brachial plexus avulsion. The anatomical diffierences among the primary afferent subtypes also affect their roles in normal and damaged conditions.El uso de las neuronas sensoriales primarias ha aportado avances en el entendimiento de las razones por las cuales falla la regeneraci贸n cuando el sistema nervioso central (SNC) es da帽ado. La rizotom铆a dorsal se puede usar como un modelo experimental de las lesiones por avulsi贸n del plexo braquial, una lesi贸n en la cual son desprendidas, en su punto de entrada en la m茅dula espinal, las ramas centrales de los aferentes primarios causando una disfunci贸n motora y sensorial grave e irreversible del miembro superior. En el presente trabajo, se examin贸 la organizaci贸n central de los aferentes primarios en ratas Wistar adultas. 脡stas fueron divididas en controles normales no lesionados y en animales rizotomizados entre los niveles cervical 3 y tor谩cico 3 (C3-T3). Se estudi贸 la deaferentaci贸n de los subtipos de axones sensoriales utilizando anticuerpos espec铆ficos contra el p茅ptido relacionado con el gen de la calcitonina (CGRP), el receptor purin茅rgico (P2X3), el receptor de baja afinidad p75 para el factor de crecimiento nervioso (NGF) y contra la subunidad 芒 de la toxina de c贸lera (TCb ). Otro subtipo fue marcado con la lectina Griffonia simplicifolia IB4. La inmunohistoqu铆mica y la microscop铆a 贸ptica de alta resoluci贸n demostraron que el modelo animal de rizotom铆a completa del plexo braquial reproduce diversos d茅ficit observados en las lesiones humanas. Esta lesi贸n produce diferentes grados de degeneraci贸n terminal entre los diversos tipos de aferentes primarios que definen subpoblaciones de neuronas sensoriales. En los niveles de la m茅dula espinal estudiados (entre C6 y C8), la deaferentaci贸n fue parcial para las fibras peptid茅rgicas GCRPpositivas, en contraste con la eliminaci贸n de las fibras no peptid茅rgicas y las mielinizadas. La rizotom铆a dorsal es un modelo experimental apropiado para estudiar las alteraciones sensoriales como el dolor agudo y la alodinia, as铆 como los factores que podr铆an afectar la regeneraci贸n en el SNC. Por tanto, la respuesta de deaferentacion diferencial debe ser tenida en cuenta para la evaluaci贸n de terapias antinociceptivas y regenerativas tras la avulsi贸n del plexo braquial. Se discute la anatom铆a de los subtipos de aferentes primarios y su papel en condiciones normales y despu茅s de la lesi贸n.Financial support for this work was provided by the European Community (Biomed II contract BMH4-97-2586), the Spanish Health Department (FIS98/0830), The British Council Programme (#8375) of Acciones Integradas and the International Spinal Research Trust. Vilma C Mu帽et贸n-G贸mez holds a Colciencias and a Fundaci贸n Carolina fellowships from the Colombian and the Spanish government respectively.Peer reviewe
Mecanismos involucrados en la promoci贸n de crecimiento axonal por la glia envolvente del bulbo olfatorio
Tyrosine hydroxylase cells appearing in the mouse striatum after dopamine denervation are likely to be projection neurones regulated by l-DOPA
Tyrosine hydroxylase (TH)-immunoreactive (ir) neurones are detected in the striatum of animals after dopamine depletion and also in human parkinsonian patients. Although there is extensive evidence for TH-ir neurones in the lesioned rodent striatum, there are few details regarding the molecular phenotype of these neurones, regulation of their TH expression after l-3,4-dihydroxyphenylalanine (L-DOPA) treatment and their function. In the present study, we examined the time-course of appearance of TH-ir neurones in the mouse striatum after 6-hydroxydopamine (6-OHDA) lesion and determined their molecular phenotype. We found that TH-ir neurones appeared in the striatum as early as 3 days after a 6-OHDA lesion. By 1 week after the lesion, the number of TH-ir neurones started to decrease and this decrease progressed significantly over time. Treatment with L-DOPA increased both the number of TH-ir neurones and the intensity of their immunolabelling. The TH-ir neurones that appear after the 6-OHDA lesion in the striatum are not newly generated cells as they did not incorporate 5-bromo-2-deoxyuridine. We found that the vast majority of TH-ir neurones colocalized with dynorphin and enkephalin, suggesting that they are projection neurones of the direct and indirect striatal output pathways. TH-ir neurones did not express the dopamine transporter but half of them expressed amino acid decarboxylase, an enzyme required for dopamine synthesis. Finally, striatal TH-ir neurones are functionally active, expressing the neuronal activation marker FosB in response to L-DOPA treatment. Promotion of these striatal TH-ir neurones may be beneficial in Parkinson's disease, particularly in the early stages when dopamine denervation is incomplete.grants from the Spanish Ministerio de Ciencia y Tecnolog铆a (SAF2003-4864, GEN2003-C06-02/NAC) and the Spanish Ministerio de Sanidad y Consumo, Fondo de Investigaci贸n Sanitaria (PI0710B, RTA RD06/0001, PNSD, CIBERNED)Peer reviewe
Neural differentiation of transplanted neural stem cells in a rat model of striatal lacunar infarction: light and electron microscopic observations
The increased risk and prevalence of lacunar stroke and Parkinson's disease (PD) makes the search for better experimental models an important requirement for translational research. In this study we assess ischemic damage of the nigrostriatal pathway in a model of lacunar stroke evoked by damaging the perforating arteries in the territory of the substantia nigra (SN) of the rat after stereotaxic administration of endothelin-1 (ET-1), a potent vasoconstrictor peptide. We hypothesized that transplantation of neural stem cells (NSCs) with the capacity of differentiating into diverse cell types such as neurons and glia, but with limited proliferation potential, would constitute an alternative and/or adjuvant therapy for lacunar stroke. These cells showed neuritogenic activity in vitro and a high potential for neural differentiation. Light and electron microscopy immunocytochemistry was used to characterize GFP-positive neurons derived from the transplants. 48 h after ET-1 injection, we characterized an area of selective degeneration of dopaminergic neurons within the nigrostriatal pathway characterized with tissue necrosis and glial scar formation, with subsequent behavioral signs of Parkinsonism. Light microscopy showed that grafted cells within the striatal infarction zone differentiated with a high yield into mature glial cells (GFAP-positive) and neuron types present in the normal striatum. Electron microscopy revealed that NSCs-derived neurons integrated into the host circuitry establishing synaptic contacts, mostly of the asymmetric type. Astrocytes were closely associated with normal small-sized blood vessels in the area of infarct, suggesting a possible role in the regulation of the blood brain barrier and angiogenesis. Our results encourage the use of NSCs as a cell-replacement therapy for the treatment of human vascular Parkinsonism.This study was supported by grants from the Spanish Ministry for Science and Innovation (SAF2007-60010, SAF2010-15173), Servicio de Salud de Castilla La Mancha Community (SESCAM), FISCAM (PI-2008/18), Mutua Madrile帽a 2010, Red Neurovascular del ISCIII (RD06/0026/1001), Fundaci贸n Alicia Koplowitz, Colciencias and LACER SA.Peer reviewedPeer Reviewe
Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation.
Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe