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1.
J Neurosci ; 44(31)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38811166

RESUMO

Neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt) that express the glucagon gene (Gcg) give rise to glucagon-like peptide 1 (GLP1)-immunopositive axons in the spinal cord and many subcortical brain regions. Central GLP1 receptor signaling contributes to motivated behavior and stress responses in rats and mice, in which hindbrain GLP1 neurons are activated to express c-Fos in a metabolic state-dependent manner. The present study examined whether GLP1 inputs to distinct brain regions arise from distinct subsets of Gcg-expressing neurons, and mapped the distribution of axon collaterals arising from projection-defined GLP1 neural populations. Using our Gcg-Cre knock-in rat model, Cre-dependent adeno-associated virus (AAV) tracing was conducted in adult male and female rats to compare axonal projections of IRt versus cNTS GLP1 neurons. Overlapping projections were observed in all brain regions that receive GLP1 input, with the caveat that cNTS injections produced Cre-dependent labeling of some IRt neurons, and vice versa. In additional experiments, specific diencephalic or limbic forebrain nuclei were microinjected with Cre-dependent retrograde AAVs (AAVrg) that expressed reporters to fully label the axon collaterals of transduced GLP1 neurons. AAVrg injected into each forebrain site labeled Gcg-expressing neurons in both the cNTS and IRt. The collective axon collaterals of labeled neurons entered the spinal cord and every brain region previously reported to contain GLP1-positive axons. These results indicate that the axons of GLP1 neural populations that innervate the thalamic paraventricular nucleus, paraventricular nucleus of the hypothalamus, and/or bed nucleus of the stria terminalis collectively innervate all central regions that receive GLP1 axonal input.


Assuntos
Axônios , Peptídeo 1 Semelhante ao Glucagon , Neurônios , Rombencéfalo , Animais , Masculino , Feminino , Ratos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/genética , Neurônios/metabolismo , Axônios/metabolismo , Rombencéfalo/metabolismo , Vias Neurais/metabolismo , Ratos Sprague-Dawley , Hipotálamo/metabolismo , Hipotálamo/citologia , Prosencéfalo/metabolismo , Sistema Límbico/metabolismo , Núcleo Solitário/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo
2.
Neuroimage ; : 120791, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147291

RESUMO

Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions. Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy-5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.

3.
J Neurophysiol ; 131(6): 1299-1310, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691532

RESUMO

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.


Assuntos
Potencial Evocado Motor , Extremidade Inferior , Músculo Esquelético , Estimulação Magnética Transcraniana , Masculino , Humanos , Músculo Esquelético/fisiologia , Potencial Evocado Motor/fisiologia , Adulto , Feminino , Extremidade Inferior/fisiologia , Córtex Motor/fisiologia , Reflexo H/fisiologia , Adulto Jovem , Tratos Piramidais/fisiologia
4.
J Neurophysiol ; 131(5): 807-814, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38505916

RESUMO

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.


Assuntos
Força da Mão , Imageamento por Ressonância Magnética , Humanos , Força da Mão/fisiologia , Adulto , Masculino , Feminino , Adulto Jovem , Tegmento Pontino/fisiologia , Tegmento Pontino/diagnóstico por imagem
5.
J Alzheimers Dis ; 99(1): 307-319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38669537

RESUMO

Background: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. Objective: To define age and AD associations of brainstem TSPO PET signal in humans. Methods: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. Results: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004). In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Conclusions: Decreased IC TSPO expression with aging and AD-an opposite pattern than in cortex-highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.


Assuntos
Envelhecimento , Doença de Alzheimer , Tronco Encefálico , Microglia , Tomografia por Emissão de Pósitrons , Receptores de GABA , Humanos , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Microglia/metabolismo , Microglia/patologia , Masculino , Idoso , Feminino , Envelhecimento/patologia , Tronco Encefálico/metabolismo , Tronco Encefálico/patologia , Receptores de GABA/metabolismo , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Isoquinolinas , Adulto
6.
Autism Res ; 17(2): 266-279, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38278763

RESUMO

Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0-10.9 years). Participants completed an assessment of core autism features and diffusion- and T1-weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0-17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation-alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA-PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA-PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio-respiration in animal models, was associated with social communication in children, while the LPB, a pain-network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Criança , Humanos , Adolescente , Transtorno Autístico/diagnóstico por imagem , Nociceptividade , Tronco Encefálico/diagnóstico por imagem , Formação Reticular
7.
Saudi J Ophthalmol ; 38(1): 59-63, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628416

RESUMO

Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. It has a wide range of manifestations and commonly affects the visual system. Many patients with MS report decreased vision, diplopia, nystagmus, and abnormal ocular motility. Nevertheless, bilateral horizontal gaze palsies are exceptionally rarely seen. We present the case of a 24-year-old female who came to our pediatric ophthalmology clinic complaining of bilateral horizontal gaze palsy, photophobia, and eye pain for 2 days. Although the patient had a family history of MS, there was no similar or previous complaint, with an unremarkable past medical and surgical history. During the examination, she was found to have a complete bilateral absence of horizontal saccade and pursuit, with slight limitations in vertical ones. There was no nystagmus or skew deviation, and the rest of the cranial nerves (CNs) were intact. Her ocular vital signs were normal, and her corrected visual acuity was 20/20 with full-color vision. The rest of the physical and neurological examinations were unremarkable. After referral to neurology, the magnetic resonance imaging showed multiple hyperintense lesions in deep white matter, pons, and midbrain. The correlation of imaging findings with clinical presentation confirmed the diagnosis of a clinically isolated syndrome. Extra-ocular motility (EOM) significantly improved after pulse steroid therapy and five sessions of plasma exchange, but the patient developed 35 prism diopter of acquired concomitant esotropia. She underwent a right medial rectus botulinum toxin injection which dramatically improved her condition, and became orthotropic during the last 2 months of follow-up after the injection.

8.
J Comp Neurol ; 532(2): e25570, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38108576

RESUMO

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented. The number and density of the labeled neurons were obtained by stringent stereological methods, whereas their topographical distribution was reported upon corresponding magnetic resonance imaging (MRI) planes. In both human and nonhuman primates, the PPN and LDTg are populated by three neurochemically distinct types of neurons (ChAT-/Nadph-δ+, ChAT+/Nadph-δ-, and ChAT+/Nadph-δ+), which are distributed according to a complex spatial interplay. Three-dimensional reconstructions reveal that ChAT+ neurons in the PPN and LDTg form a continuum with some overlaps with pigmented neurons of the locus coeruleus, dorsally, and of the substantia nigra (SN) complex, ventrally. The ChAT+ neurons in the PPN and LDTg are -two to three times more numerous in humans than in monkeys but their density is -three to five times higher in monkeys than in humans. Neurons expressing both ChAT and Nadph-δ have a larger cell body and a longer primary dendritic arbor than singly labeled neurons. Stereological quantification reveals that 25.6% of ChAT+ neurons in the monkey PPN are devoid of Nadph-δ staining, a finding that questions the reliability of Nadph-δ as a marker for cholinergic neurons in primate brainstem.


Assuntos
Tronco Encefálico , Tegmento Mesencefálico , Animais , Humanos , Reprodutibilidade dos Testes , Tronco Encefálico/metabolismo , Neurônios Colinérgicos/metabolismo , Colinérgicos , Colina O-Acetiltransferase/metabolismo
9.
J Comp Neurol ; 532(2): e25590, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38335045

RESUMO

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system (CNS) of vertebrates. Immunohistochemical techniques with specific antibodies against GABA or against its synthesizing enzyme, glutamic acid decarboxylase (GAD) allowed characterizing GABAergic neurons and fibers in the CNS. However, studies on the CNS distribution of GABAergic neurons and fibers of bony fishes are scant and were done in teleost species. With the aim of understanding the early evolution of this system in bony vertebrates, we analyzed the distribution of GABA-immunoreactive (-ir) and GAD-ir neurons and fibers in the CNS of a basal ray-finned fish, the Siberian sturgeon (Chondrostei, Acipenseriformes), using immunohistochemical techniques. Our results revealed the presence and distribution of GABA/GAD-ir cells in different regions of the CNS such as olfactory bulbs, pallium and subpallium, hypothalamus, thalamus, pretectum, optic tectum, tegmentum, cerebellum, central grey, octavolateralis area, vagal lobe, rhombencephalic reticular areas, and the spinal cord. Abundant GABAergic innervation was observed in most brain regions, and GABAergic fibers were very abundant in the hypothalamic floor along the hypothalamo-hypophyseal tract and neurohypophysis. In addition, GABA-ir cerebrospinal fluid-contacting cells were observed in the alar and basal hypothalamus, saccus vasculosus, and spinal cord central canal. The distribution of GABAergic systems in the sturgeon brain shows numerous similarities to that observed in lampreys, but also to those of teleosts and tetrapods.


Assuntos
Encéfalo , Sistema Nervoso Central , Animais , Peixes , Medula Espinal , Ácido gama-Aminobutírico
10.
Rev. habanera cienc. méd ; 19(5): e3113, sept.-oct. 2020. ilus
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1144686

RESUMO

RESUMEN Introducción: El manejo diagnóstico y terapéutico en los pacientes con lupus eritematoso sistémico que desarrollan una afectación neuropsiquiátrica representa un reto, debido a la heterogeneidad de las formas en que puede presentarse y la ausencia de criterios diagnósticos. Objetivo: Reconocer las formas clínicas de presentación de los síndromes neuroftalmológicos que traducen afectación pontina. Presentación del caso: Hombre de 71 años con antecedente de lupus eritematoso sistémico con afectación neuopsiquiátrica, que de forma aguda desarrolla un cuadro emético en el curso de una emergencia hipertensiva seguido de una parálisis de la mirada horizontal hacia la izquierda, una oftalmoplejía internuclear posterior derecha y una parálisis facial izquierda. En la neuroimagen se constata una afectación multifocal con marcado daño pontino. Conclusiones: Reconocer las formas clínicas de presentación de estos trastornos neuroftalmológicos raros que generalmente se presentan de forma aguda/subaguda permite al neurólogo realizar el diagnóstico topográfico de la lesión a nivel protuberancial con elevada precisión desde la Sala de Urgencias, así como reducir los posibles diagnósticos diferenciales a una etiología vascular, desmielinizante u ocupativa de espacio(AU)


ABSTRACT Introduction: The diagnostic and therapeutic management of patients with systemic lupus erythematosus who develop a neuropsychiatric involvement represents one of the biggest challenges due to the heterogeneity of the ways in which it can occur and the absence of diagnostic criteria. Objective: To recognize the clinical forms of presentation of neurophthalmological syndromes that express pontine involvement. Case presentation: Seventy-one-year-old man with history of systemic lupus erythematosus with neuropsychiatric involvement who acutely develops an emetic episode in the course of a hypertensive emergency followed by a paralysis of the horizontal gaze to the left, a right-sided posterior internuclear ophthalmoplegia and a left facial palsy. In the neuroimaging, a multifocal involvement with marked pontine damage is observed. Conclusions: Recognizing the clinical forms of presentation of these rare neurophthalmological disorders that generally occur in an acute or subacute form allows the neurologist to perform the topographic diagnosis of the lesion at a protuberancial level with high precision from the time when the patient attends the Emergency Department and reduces the possible differential diagnoses to a vascular, demyelinating or occupational etiology of space(AU)


Assuntos
Humanos , Masculino , Idoso , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Diagnóstico Diferencial
11.
Acta neurol. colomb ; 34(1): 70-84, 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-949613

RESUMO

RESUMEN INTRODUCCIÓN: Los pacientes con trauma craneoencefálico severo pueden tener secuelas neurológicas graves que generan discapacidad de rangos diferentes según la escala de Barthel. La alteración del estado de consciencia es la secuela más grave y es causa de dependencia completa de estos pacientes por la pérdida del autocuidado. La relación entre los hallazgos anormales en las neuroimágenes y los diferentes estados de conciencia ha sido objeto de investigación en los últimos años, con la posibilidad de que existan nuevas opciones con el posproceso de imágenes obtenidas por resonancia magnética nuclear. Este estudio pretende describir las alteraciones en la difusibilidad media haciendo posproceso en la secuencia de DWI en 4 pacientes con trauma craneoencefálico severo y alteración del estado de consciencia, quienes en la fase aguda del trauma fueron estudiados con imágenes convencionales de tomografía y resonancia. MATERIALES Y MÉTODOS: Se describe una serie de 4 casos de pacientes con trauma craneoencefálico severo y alteración del estado de consciencia a quienes se realizó resonancia cerebral simple. Las imágenes fueron sometidas a un posproceso de la secuencia de DWI analizando diferentes regiones por donde transcurren las fibras del sistema reticular activador ascendente (SRAA) (cuerpos restiformes, rafe medio del mesencéfalo, tálamo, regiones subinsulares y lóbulos frontales basales). Igualmente se tomaron valores de difusibilidad en regiones similares, en 5 sujetos sin alteración estructural cerebral tomados como controles. RESULTADOS: Se encontró disminución en la difusibilidad media en las diferentes regiones establecidas en el estudio, que tuvieron diferente localización en cada paciente. Los valores disminuyeron aproximadamente en un 50 % respecto a los del grupo control, observando lesiones en áreas que no fueron identificadas en la interpretación de la imagen cuando fue adquirida durante el trauma. CONCLUSIONES: El posproceso de la secuencia DWI muestra disminución en los valores de difusibilidad media en regiones por donde transcurren las vías del sistema reticular activado ascendente, estos cambios que explican las diferentes alteraciones en el estado de conciencia, no fueron visualizados en las imágenes interpretadas bajo las técnicas convencionales. Se requiere nuevos estudios para establecer las características operativas de la prueba que permitan definir su potencial utilidad dentro de los algoritmos de clasificación inicial de los pacientes con trauma craneoencefálico severo.


SUMMARY INTRODUCTION: Patients with severe traumatic brain injury may have severe neurological sequelae that generate disability of different ranges, according to the Barthel scale. The consciousness impairment is the most serious sequela and is a cause of complete dependence of these patients, due to the loss of self-care. The relationship between abnormal findings in neuroimaging and different states of consciousness has been the subject of research in recent years, with the possibility of new options with the post-processing of magnetic resonance imaging (MRI). This study aims to describe the alterations in the mean diffusivity by post-processing of the diffusion weighted imaging (DWI) sequence in 4 patients with severe traumatic brain injury and impairment of consciousness, who were studied with computed tomography (CT) and MRI in the acute phase of the trauma. MATERIALS AND METHODS: We describe a series of 4 cases of patients with severe traumatic brain injury and impaired consciousness in whom a non-enhanced brain MRI was performed. The DWI sequence images were post-processed, analyzing different regions through which the fibers of the Ascending Reticular Activating System (ARAS) (including restiform bodies, midbrain, thalamus, sub-insular regions and basal frontal lobes) pass. Likewise, diffusivity values were taken in similar regions, in 5 subjects without any structural brain abnormality, who were taken as controls. RESULTS: There was a decrease in mean diffusivity in the different regions established in the study, which had different locations in each patient. Values decreased approximately 50 percent from values in normal patients. After post-processing, some lesions were observed in areas that were not identified in the initial MRI interpretation during the trauma. CONCLUSIONS: The post-processing of the DWI sequence shows a decrease in the mean diffusivity values in regions where the ARAS pathways pass through. These changes explaining the different alterations in consciousness were not visualized in the images interpreted under conventional MRI techniques. New studies are required to establish the operative characteristics of this test, that allow to define its potential utility within the algorithms of initial classification of patients with severe traumatic brain injury.


Assuntos
Formação Reticular , Imagem de Difusão por Ressonância Magnética , Lesões Encefálicas Traumáticas
12.
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1088663

RESUMO

El estudio de las estrategias neurales para la organización del comportamiento en vertebrados constituye un desafío mayor para la Neurociencia. El avance del conocimiento en este campo depende de manera crítica de la utilización de modelos experimentales adecuados que admitan múltiples niveles de análisis (p.ej: comportamental, circuital, celular, sináptico, molecular) y abordajes multitécnicos. Nos propusimos analizar in vitro una red neural de la unión mesopontina del tronco encefálico críticamente implicada en el control del sueño de movimientos oculares rápidos (S-REM). Pese al cúmulo de evidencias que apoyan el papel desempeñado por esta red en relación al S-REM, los mecanismos celulares y sinápticos que subyacen a este control son poco conocidos y continúan siendo objeto de intensa investigación. Para avanzar en el conocimiento de estos mecanismos, se llevó a cabo la caracterización morfológica y funcional de una rodaja de tronco encefálico de la rata, en la que las estructuras críticas para el control del S-REM, i.e.: núcleos tegmentales laterodorsal y pedúnculopontino, y su proyección al núcleo reticular pontis oralis (PnO), están presentes y son operativas. La inclusión del núcleo motor del trigémino en la rodaja permitió detectar cambios de la excitabilidad de las motoneuronas ante manipulaciones farmacológicas del PnO, representativos de los cambios del tono muscular asociados a maniobras similares realizadas in vivo. La utilización de este modelo in vitro de S-REM, permitirá aportar a la dilucidación de las estrategias neurales que operan en niveles intermedios de organización del SN en mamíferos para la generación y regulación de un estado comportamental.


The study of the neural basis of behavior is a major challenge in Neuroscience. Advancing our knowledge in this field depends, critically, on the use of experimental paradigms that provide multiple levels of analysis, as well as powerful techniques. We have selected, as a model of a neural plan that organizes a complex behavior, a neural network located in the mesopontine junction. This region is thought to be both necessary and sufficient for the generation of rapid eye movement (REM) sleep, although the cellular and synaptic mechanisms involved in the control of this behavioral state at the mesopontine level are still under debate and remain poorly understood. As part of a long term effort to gain insight into these mechanisms, we carried out the morphological and functional characterization of a slice preparation of rat brainstem and we demonstrate that critical structures for the control of REM sleep - the laterodorsal and pedunculopontine tegmental nuclei and their projection to the oral part of the pontine reticular nucleus (PnO) - are present and are operational. The presence of the trigeminal motor nucleus in the slice sought to include in the experimental model a structure capable of expressing changes of the excitability of the motorneurons caused by pharmacological manipulations of the PnO, representative of changes of muscle tone associated with similar maneuvers performed in vivo. The use of this in vitro model of REM sleep will provide critical information to elucidate neural strategies that operate at intermediate levels of central nervous system organization in mammals to control behavioral states.


O estudo de estratégias neurais para a organização do comportamento em vertebrados constitui um desafio maior para a Neurociencia. O avanço do conhecimento nessa área depende criticamente da utilização de modelos experimentais adequados que suportem múltiplos níveis de análise (por exemplo: comportamental, circuital, celular, sináptico e molecular) e abordagens por múltiplas técnicas. Decidiu-se analisar in vitro uma rede neural da união mesopontina do tronco encefálico criticamente envolvida no controle do sono de movimentos oculares rápidos (S-REM). Apesar da riqueza de provas que sustentam o papel desta rede em relação ao S-REM, os mecanismos celulares e sinápticos subjacentes a este controle são pouco conhecidos e permanecem sob intensa investigação. Para avançar no conhecimento desses mecanismos, caracterizou-se morfológica e funcionalmente uma fatia de tronco encefálico de rato, na qual as estruturas críticas para o controle do S-REM, i.e.: núcleos tegmentais laterodorsal e pedunculopontino, e sua projeção para o núcleo reticular pontis oralis (PnO) estão presentes e operantes. A inclusão do núcleo motor do trigêmeo na fatia permitiu detectar mudanças da excitabilidade das motoneuronas provocadas por manipulações farmacológicas do PnO, representativas das alterações do tônus muscular associados com operações semelhantes quando realizados in vivo. A utlização deste modelo in vitro de S-REM permitirá contribuir para a elucidação de estratégias neurais que operam em níveis intermedios de organização do SN de mamíferos para a geração e regulação de um estado comportamental.


Assuntos
Animais , Ratos , Sono REM/fisiologia , Vigília/fisiologia , Polissonografia , Neurônios/fisiologia , Técnicas In Vitro , Tronco Encefálico/anatomia & histologia , Ratos Wistar , Estimulação Elétrica , Fenômenos Eletrofisiológicos
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