RESUMEN

The number of functionally active synapses provides a measure of neural integrity, with reductions observed in neurodegenerative disorders. [11C]UCB-J binds to synaptic vesicle 2A (SV2A) transmembrane protein located in secretory vesicles. We aimed to assess [11C]UCB-J PET as an in vivo biomarker of regional cerebral synaptic SV2A density in rat lesion models of neurodegeneration. Healthy anesthetized rats had [11C]UCB-J PET and arterial blood sampling. We compared different models describing [11C]UCB-J brain uptake kinetics to determine its regional distribution. Blocking studies were performed with levetiracetam (LEV), an antiepileptic SV2A antagonist. Tracer binding was measured in rodent unilateral acute lesion models of Parkinsonism and Huntington's disease, induced with 6-hydroxydopamine (6-OHDA) and quinolinic acid (QA), respectively. [3H]UCB-J autoradiography was performed in postmortem tissue. Rat brain showed high and fast [11C]UCB-J uptake and washout with up to 80% blockade by LEV. [11C]UCB-J PET showed a 6.2% decrease in ipsilateral striatal SV2A binding after 6-OHDA and 39.3% and 55.1% decreases after moderate and high dose QA confirmed by autoradiography. In conclusion, [11C]UCB-J PET provides a good in vivo marker of synaptic SV2A density which can potentially be followed longitudinally along with synaptic responses to putative neuroprotective agents in models of neurodegeneration.

Asunto(s)

Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/lesiones , Glicoproteínas de Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Tomografía de Emisión de Positrones/métodos , Sinapsis/metabolismo , Animales , Anticonvulsivantes/farmacología , Autorradiografía , Femenino , Enfermedad de Huntington/inducido químicamente , Enfermedad de Huntington/patología , Enfermedad de Huntington/psicología , Hidroxidopaminas/farmacocinética , Cinética , Levetiracetam/farmacología , Glicoproteínas de Membrana/antagonistas & inhibidores , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/patología , Enfermedad de Parkinson Secundaria/psicología , Ácido Quinolínico/farmacocinética , Radiofármacos , Ratas , Ratas Sprague-Dawley

RESUMEN

Introducción. La gran vulnerabilidad a la isquemia de la región estriatocapsular hace que la trombectomía mecánica tenga sus limitaciones en las oclusiones de vaso de gran calibre a la hora de evitar que la región estriatocapsular se infarte. Objetivos. Analizar el efecto del tratamiento endovascular en la incidencia de infarto estriatocapsular aislado (IECa) y describir sus características clínicas. Pacientes y métodos. Estudio retrospectivo en el que se analiza la incidencia de IECa tras el tratamiento de reperfusión cerebral. Se describen las características basales y clínicas de los pacientes identificados con IECa y se compara la incidencia del IECa entre dos grupos según la disponibilidad de trombectomía mecánica: uno (grupo pretrombectomía) que recibió fibrinólisis intravenosa como único tratamiento de reperfusión cerebral disponible en ese momento, y otro (grupo postrombectomía) que recibió trombectomía mecánica con o sin fibrinólisis intravenosa. Resultados. Del total de 390 pacientes reperfundidos, un 8,2% tuvo un IECa. De 135 pacientes tratados con fibrinólisis intravenosa, un 4,4% (n = 6) desarrolló un IECa (grupo pretrombectomía), y de 255 pacientes tratados en el grupo postrombectomía, se visualizó IECa en un 10,2%. El análisis estadístico de la incidencia de IECa entre ambos grupos mostró diferencias significativas (p = 0,034). La clínica sensomotora fue la más frecuente entre los pacientes con IECa (63,33%), con una frecuencia de síntomas corticales de un 55,17%. Conclusiones. Según los datos, hemos presenciado un aumento en la incidencia de IECa en nuestro medio tras la instauración de la trombectomía mecánica

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Introduction. The great vulnerability of the striatocapsular region to ischaemia means that mechanical thrombectomy has its limitations in occlusions of large-calibre vessels when it comes to preventing the striatocapsular region from undergoing infarction. Aims. To analyse the effect of endovascular treatment on the incidence of isolated striatocapsular infarction (iSCI) and to describe its clinical characteristics. Patients and methods. We conducted a retrospective study to analyse the incidence of iSCI following treatment of cerebral reperfusion. The baseline and clinical characteristics of the patients identified with iSCI and the incidence of iSCI is compared between two groups according to the availability of mechanical thrombectomy: one (pre-thrombectomy group) that received intravenous fibrinolysis as the only treatment for cerebral reperfusion available in that moment; and another (post-thrombectomy group) that received a mechanical thrombectomy with or without intravenous fibrinolysis. Results. Of the 390 patients who received reperfusion, 8.2% had iSCI. Of the 135 patients treated with intravenous fibrinolysis, 4.4% (n = 6) developed iSCI (pre-thrombectomy group), and of the 255 patients treated in the post-thrombectomy group, iSCI was observed in 10.2%. The statistical analysis of the incidence of iSCI between the two groups showed significant differences (p = 0.034). A sensory-motor clinical picture was the most frequent among the patients with iSCI (63.33%), with a frequency of cortical symptoms of 55.17%. Conclusions. According to the data, there has been an increase in the incidence of iSCI in our setting following the establishment of mechanical thrombectomy

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Trombectomía/métodos , Cuerpo Estriado/lesiones , Infarto Encefálico/fisiopatología , Reperfusión , Isquemia Encefálica/terapia , Infarto Encefálico/cirugía , Terapia Trombolítica/métodos , Estudios Retrospectivos

RESUMEN

Basal ganglia (BG) lesions cause impairments of different mammalian's movement and cognition behaviors. Motor circuit impairment has a dominant role in the movement disorders. An inhibitory factor in BG is GABA neurotransmitter, which is released from striatum. Lesions in GABAergic neurons could trigger movement and cognition disorders. Previous evidence showed that GABAB receptor agonist (Baclofen) administration in human improves movement disorders and exercise can improve neurodegenerative and cognitive decline; however, the effects of both Baclofen and mild forced treadmill exercise on movement disorders are not well known. The main objective of this study is to investigate the combined effects of mild forced treadmill exercise and microinjection of Baclofen in the internal Globus Pallidus on striatum lesion-induced impairments of spatial learning and motor activity. We used Morris water maze and open filed tests for studying spatial learning, and motor activity, respectively. Results showed that mild exercise and Baclofen microinjection could not lonely affect the spatial learning, and motor activity impairments while the combination of them could alleviate spatial learning, and motor activity impairments in striatum-lesion animals. Our results suggest that striatum lesion-induced memory and motor activity impairments can improve with combination interaction of GABAB receptor agonist and exercise training.

Asunto(s)

Baclofeno/farmacología , Cuerpo Estriado/lesiones , Agonistas de Receptores GABA-B/fisiología , Memoria/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Esfuerzo Físico/fisiología , Aprendizaje Espacial/efectos de los fármacos , Animales , Baclofeno/administración & dosificación , Agonistas de Aminoácidos Excitadores/farmacología , Agonistas de Receptores GABA-B/administración & dosificación , Globo Pálido , Ácido Iboténico/farmacología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Microinyecciones , Ratas , Ratas Wistar

RESUMEN

The endocannabinoid system (ECS) actively participates in several physiological processes within the central nervous system. Among such, its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been established. After its production via the kynurenine pathway (KP), quinolinic acid (QUIN) can act as an excitotoxin through the selective overactivation of NMDAr, thus participating in the onset and development of neurological disorders. In this work, we evaluated whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by URB597, and the consequent increase in the endogenous levels of anandamide, can prevent the excitotoxic damage induced by QUIN. URB597 (0.3 mg/kg/day × 7 days, administered before, during and after the striatal lesion) exerted protective effects on the QUIN-induced motor (asymmetric behavior) and biochemical (lipid peroxidation and protein carbonylation) alterations in rats. URB597 also preserved the structural integrity of the striatum and prevented the neuronal loss (assessed as microtubule-associated protein-2 and glutamate decarboxylase localization) induced by QUIN (1 µL intrastriatal, 240 nmol/µL), while modified the early localization patterns of CBr1 (CB1) and NMDAr subunit 1 (NR1). Altogether, these findings support the concept that the pharmacological manipulation of the endocannabinoid system plays a neuroprotective role against excitotoxic insults in the central nervous system.

Asunto(s)

Amidohidrolasas/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Ácido Quinolínico/farmacología , Receptor Cannabinoide CB1/efectos de los fármacos , Animales , Ácidos Araquidónicos/farmacología , Cuerpo Estriado/lesiones , Endocannabinoides/farmacología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Alcamidas Poliinsaturadas/farmacología , Ratas Wistar , Receptor Cannabinoide CB1/metabolismo

RESUMEN

Introducción: Las áreas motoras corticales no solo son influenciadas por aferencias sensitivas periféricas y áreas de asociación prefrontales, sino también por los ganglios basales, específicamente el estriado. El estriado dorsomedial (EDM) y el estriado dorsolateral están involucrados en el aprendizaje espacial y el aprendizaje estímulo-respuesta; sin embargo, cada una de estas zonas pudiera mediar distintos componentes del aprendizaje. El propósito del estudio es determinar el efecto de la lesión electrolítica del EDM sobre el aprendizaje y ejecución de la conducta locomotora y sexual en ratas macho. Método: Una vez que los sujetos aprendieron a ejecutar las pruebas motoras de equilibrio, laberinto, rampa de ascenso y la conducta sexual, se realizó la lesión electrolítica del EDM. Cinco días después se realizaron las pruebas en 2 ocasiones más y se compararon las latencias de ejecución de cada prueba. Resultados: Después de la lesión, los valores promedio de latencia, incrementaron durante la ejecución de las pruebas de laberinto y equilibrio. Sin embargo, los valores promedio en la prueba rampa y conducta sexual, no aportaron efectos contrastantes entre los grupos. Conclusiones: La lesión electrolítica del EDM modifica la ejecución de la actividad locomotora (prueba de laberinto y equilibrio), pero no la ejecución de la conducta sexual (AU)

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Introduction: Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Method: Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Results: Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Conclusions: Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behavior (AU)

Asunto(s)

Animales , Ratas , Cuerpo Estriado/lesiones , Conducta Sexual , Locomoción/fisiología , Ratas/fisiología , Aprendizaje por Laberinto/fisiología , Electrólisis/efectos adversos , Lesión Encefálica Crónica/fisiopatología

RESUMEN

Repetitive stimulation of cognitive forebrain circuits at frequencies capable of inducing corticostriatal long term plasticity is increasingly being used with therapeutic purposes in patients with neuropsychiatric disorders. However, corticostriatal plasticity is rarely studied in the intact brain. Our aim was to study the mechanisms of corticostriatal long term depression (LTD) induced by high frequency stimulation (HFS) of the medial prefrontal cortex in vivo. Our main finding is that the LTD induced in the dorsomedial striatum by medial prefrontal cortex HFS in vivo (prefrontostriatal LTD) is not affected by manipulations that block or reduce the LTD induced in the dorsolateral striatum by motor cortex HFS in brain slices, including pharmacological dopamine receptor and CB1 receptor blockade, chronic nigrostriatal dopamine depletion, CB1 receptor genetic deletion and selective striatal cholinergic interneuron (SCIN) ablation. Conversely, like in the hippocampus and other brain areas, prefrontostriatal LTD is NMDA receptor dependent. Thus, we describe a novel form of corticostriatal LTD that operates in brain circuits involved in reward and cognition and could be relevant for understanding the therapeutic effects of deep brain stimulation.

Asunto(s)

Cuerpo Estriado/citología , Cuerpo Estriado/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Neuronas/fisiología , Corteza Prefrontal/fisiología , Adrenérgicos/toxicidad , Animales , Animales Recién Nacidos , Benzazepinas/farmacología , Colina O-Acetiltransferasa/genética , Colina O-Acetiltransferasa/metabolismo , Cuerpo Estriado/lesiones , Maleato de Dizocilpina/farmacología , Antagonistas de Dopamina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Factor de Crecimiento Similar a EGF de Unión a Heparina/genética , Factor de Crecimiento Similar a EGF de Unión a Heparina/metabolismo , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Depresión Sináptica a Largo Plazo/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Oxidopamina/toxicidad , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Tirosina 3-Monooxigenasa/metabolismo

RESUMEN

Nigrostriatal pathway injury is one of the traumatic brain injury models that usually lead to neurological dysfunction or neuron necrosis. Resveratrol-induced benefits have recently been demonstrated in several models of neuronal degeneration diseases. However, the protective properties of resveratrol against neurodegeneration have not been explored definitely. Thus, we employ the nigrostriatal pathway injury model to mimic the insults on the brain. Resveratrol decreased the p-ERK expression and increased the p-JNK expression compared to the DMSO group, but not alter the p38 MAPK proteins around the lesion site by Western blot. Prior to the injury, mice were infused with resveratrol intracerebroventricularly with or without JNK-IN-8, a specific c-JNK pathway inhibitor for JNK1, JNK2 and JNK4. The study assessed modified improved neurological function score (mNSS) and beam/walking test, the level of inflammatory cytokines IL-1ß, IL-6 and TNF-α, and striatal expression of Bax and Bcl-2 proteins associated with neuronal apoptosis. The results revealed that resveratrol exerted a neuroprotective effect as shown by the improved mNSS and beam latency, anti-inflammatory effects as indicated by the decreased level of IL-1ß, TNF-α and IL-6. Furthermore, resveratrol up-regulated the protein expression of p-JNK and Bcl-2, down-regulated the expression of Bax and the number of Fluoro-Jade C (FJC) positive neurons. However, these advantages of resveratrol were abolished by JNK-IN-8 treatment. Overall, we demonstrated that resveratrol treatment attenuates the nigrostriatal pathway injury-induced neuronal apoptosis and inflammation via activation of c-JNK signaling.

Asunto(s)

Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Cuerpo Estriado/efectos de los fármacos , MAP Quinasa Quinasa 4/metabolismo , Fármacos Neuroprotectores/farmacología , Estilbenos/farmacología , Sustancia Negra/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/enzimología , Lesiones Traumáticas del Encéfalo/patología , Cuerpo Estriado/enzimología , Cuerpo Estriado/lesiones , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , MAP Quinasa Quinasa 4/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/enzimología , Vías Nerviosas/lesiones , Vías Nerviosas/patología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/enzimología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/patología , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Fosforilación , Distribución Aleatoria , Resveratrol , Sustancia Negra/enzimología , Sustancia Negra/lesiones , Sustancia Negra/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo

RESUMEN

Neurological insults affect both, brain structure and behavior. The injury-induced brain plasticity and associated changes in behavior are difficult to study using classical histological methods. The magnetic resonance imaging (MRI), however, enables repeated inspection of the brain in the same individual. Here we took advantage of the songbird model with discrete brain circuitry controlling song learning and production and assessed if a conventional MRI is suitable to detect even relatively small brain changes. Our aim was to monitor injury and the following regeneration in the striatal vocal nucleus Area X that controls vocal learning in juveniles and affects song in adult songbird zebra finch (Taeniopygia guttata). The regeneration process was detected using T2-weighted images and validated by immunohistochemical (IHC) staining up to 6 months after the injury. Despite the small volume of the zebra finch brain, a satisfactory signal-to-noise ratio was achieved with reasonably short measurement times. No significant difference was found between the measurements of the lesion size obtained by MRI and IHC staining. Our data show that the non-invasive MRI technique can reliably measure and quantify the regeneration process even in a relatively small part of the brain and that the avian striatum progressively regenerates after its neurotoxic injury.

Asunto(s)

Envejecimiento/patología , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/patología , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/lesiones , Regeneración Nerviosa/fisiología , Animales , Lesiones Encefálicas/fisiopatología , Cuerpo Estriado/patología , Pinzones/anatomía & histología , Pinzones/lesiones , Aumento de la Imagen , Imagen por Resonancia Magnética , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury in experimental stroke, but a possible role in brain injury following global ischemia has to date not been investigated. Using a mouse bilateral occlusion model of transient global ischemia which produced surprisingly widespread injury to cortex, striatum, and hippocampus, we show here that 12/15-LOX is increased in a time-dependent manner in the vasculature and neurons of both cortex and hippocampus. Furthermore, 12/15-LOX co-localized with apoptosis-inducing factor (AIF), a mediator of non-caspase-related apoptosis in the cortex. In contrast, caspase-3 activation was more prevalent in the hippocampus. 12/15-lipoxygenase knockout mice were protected against global cerebral ischemia compared to wild-type mice, accompanied by reduced neurologic impairment. The lipoxygenase inhibitor LOXBlock-1 similarly reduced neuronal cell death both when pre-administered and when given at a therapeutically relevant time point 1 h after onset of ischemia. These findings suggest a pivotal role for 12/15-LOX in both caspase-dependent and caspase-independent apoptotic pathways following global cerebral ischemia and suggest a novel therapeutic approach to reduce brain injury following cardiac arrest.

Asunto(s)

Araquidonato 12-Lipooxigenasa/metabolismo , Araquidonato 15-Lipooxigenasa/metabolismo , Lesiones Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Neuronas/metabolismo , Animales , Apoptosis , Factor Inductor de la Apoptosis/metabolismo , Araquidonato 12-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/genética , Corteza Cerebral/lesiones , Corteza Cerebral/metabolismo , Cuerpo Estriado/lesiones , Cuerpo Estriado/metabolismo , Hipocampo/lesiones , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados

RESUMEN

Traumatic brain injury triggers a series of damaged processes, such as neuronal death and apoptosis, inflammation and scar formation, which contribute to evolution of brain injury. The present study investigated the neuroprotective effects of batroxobin, a drug widely used clinically for ischemia, in a nigrostriatal pathway injury model. Mice subjected to the nigrostriatal pathway injury were injected with batroxobin (30 BU/kg) or vehicle immediately after injury. The behavioral studies showed that batroxobin could improve the motor function in injured mice in long term. Batroxobin also reduced neuronal apoptosis and inflammation at the acute stage. Moreover, administration of batroxobin attenuated the scar formation and reduced the lesion size at 4 and 14days after brain injury. These results suggest that batroxobin has beneficial effects on the nigrostriatal pathway injury, indicating a potential clinical application.

Asunto(s)

Batroxobina/farmacología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/lesiones , Fármacos Neuroprotectores/farmacología , Sustancia Negra/efectos de los fármacos , Sustancia Negra/lesiones , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Cicatriz/tratamiento farmacológico , Cicatriz/inmunología , Cicatriz/patología , Cuerpo Estriado/inmunología , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/inmunología , Vías Nerviosas/lesiones , Vías Nerviosas/patología , Distribución Aleatoria , Sustancia Negra/inmunología , Sustancia Negra/patología

RESUMEN

The striatum is a key structure involved in reward processing and choice. Recently, we have developed a paradigm to explore how components of reward processing work together or independently during choice behavior. These components include reward discrimination, preference and relative valuation, and the goal of the present study was to determine how the striatum is involved in these dissociable components during this novel free choice paradigm. We tested choice utilizing two different outcome series with one being a more straightforward single-option discrimination anchored by a 0 reward outcome, and the other as a multi-option outcome discrimination of greater difficulty. We compared the free choice reward task to a sequential reward task and an extinction task. Striatal lesions impaired responding only in the free choice version with alterations in both appetitive and consummatory measures. Ventral striatal lesions had greater impact altering discrimination, preference and relative valuation in both the single and multi-option week studies. A major factor involved in these deficits was a significant aversion to the multi-option that contained a larger outcome option but with a longer delay to reward. Dorsal striatal lesions caused less impairment even leading to enhanced choice behavior compared to control animals during the more difficult multi-option free choice series. Overall, the results suggest that the context of action is crucial when linking striatal function to choice behavior and its diverse components. The implications include the idea that striatal involvement in decision-making is increased when responses are self-paced and diverse in a more naturalistic environment.

Asunto(s)

Lesiones Encefálicas/fisiopatología , Conducta de Elección/fisiología , Cuerpo Estriado/lesiones , Discriminación en Psicología/fisiología , Recompensa , Animales , Extinción Psicológica , Masculino , Ratas , Ratas Sprague-Dawley

RESUMEN

Songbirds, like humans, learn vocalizations and their striatum recruits new neurons in adulthood. Injury in striatal vocal nucleus Area X, involved in song learning and production in songbirds, is followed by massive regeneration. The newborn neurons arise from the subventricular zone (SVZ) rich in dopamine D3 receptors (D3Rs). The aim of this study was to investigate whether the D3Rs affect the rate of neuronal recovery in Area X. Male zebra finches (Taeniopygia guttata) received bilateral neurotoxic lesion of Area X and were implanted with osmotic minipumps containing D3R agonist 7-OH-DPAT, antagonist U99194, or saline. Treatment with 7-OH-DPAT but not U99194 led to significant reduction of lesion size and increased numbers of migrating neuroblasts and newborn cells in the Area X. These cells were detected in the lesion border as well as the lesion center. Lesion also led to increased mRNA expression of the D3Rs in the neurogenic SVZ and in the nucleus robustus arcopallialis (RA) involved in song production. Moreover, lesion alone prolonged the song duration and this may be facilitated by D3Rs in RA. Parallel lesion and stimulation of D3Rs prolonged it even more, while blocking of D3Rs abolished the lesion-induced effect. These data suggest that D3R stimulation after striatal injury accelerates the striatal recovery and can cause behavioral alterations.

Asunto(s)

Proteínas Aviares/metabolismo , Cuerpo Estriado/lesiones , Cuerpo Estriado/metabolismo , Pinzones/fisiología , Receptores de Dopamina D3/metabolismo , Vocalización Animal/fisiología , Animales , Proteínas Aviares/agonistas , Proteínas Aviares/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Dopaminérgicos/farmacología , Ácido Iboténico , Indanos/farmacología , Masculino , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , ARN Mensajero/metabolismo , Receptores de Dopamina D3/agonistas , Receptores de Dopamina D3/antagonistas & inhibidores , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Nicho de Células Madre/efectos de los fármacos , Nicho de Células Madre/fisiología , Tetrahidronaftalenos/farmacología , Vocalización Animal/efectos de los fármacos

RESUMEN

UNLABELLED: The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue-response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel "other" task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue-response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT: Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems operate independently and in parallel when rats learn one type of task at a time, but interact cooperatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex.

Asunto(s)

Cuerpo Estriado/fisiología , Señales (Psicología) , Hipocampo/fisiología , Memoria/fisiología , Retención en Psicología/fisiología , Aprendizaje Espacial/fisiología , Análisis de Varianza , Animales , Cuerpo Estriado/lesiones , Hipocampo/lesiones , Masculino , Aprendizaje por Laberinto/fisiología , Vías Nerviosas/fisiología , Ratas , Ratas Long-Evans

RESUMEN

Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration.

Asunto(s)

Cicatriz/prevención & control , Cuerpo Estriado/patología , Reacción a Cuerpo Extraño/prevención & control , Gliosis/prevención & control , Grafito/farmacología , Ventrículos Laterales/patología , Nanoestructuras/administración & dosificación , Regeneración Nerviosa/efectos de los fármacos , Células-Madre Neurales/citología , Neurogénesis/efectos de los fármacos , Prótesis e Implantes/efectos adversos , Andamios del Tejido , Animales , Astrocitos/efectos de los fármacos , Astrocitos/fisiología , Movimiento Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/toxicidad , Coloides , Cuerpo Estriado/lesiones , Cuerpo Estriado/fisiología , Capacidad Eléctrica , Conductividad Eléctrica , Reacción a Cuerpo Extraño/etiología , Grafito/administración & dosificación , Inflamación , Ventrículos Laterales/lesiones , Ventrículos Laterales/fisiología , Masculino , Ensayo de Materiales , Microglía/efectos de los fármacos , Microglía/fisiología , Microtecnología , Nanoestructuras/efectos adversos , Ratas , Ratas Wistar , Andamios del Tejido/efectos adversos

RESUMEN

Stereotypy can be characterized as inflexible, repetitive behaviors that occur following repeated exposure to psychostimulants, such as cocaine (COC). Stereotypy may be related to preferential activation of the patch (striosome) compartment of striatum, as enhanced relative activation of the patch compartment has been shown to positively correlate with the emergence of stereotypy following repeated psychostimulant treatment. However, the specific contribution of the patch compartment to COC-induced stereotypy following repeated exposure is unknown. To elucidate the involvement of the patch compartment to the development of stereotypy following repeated COC exposure, we determined if destruction of this sub-region altered COC-induced behaviors. The neurons of the patch compartment were ablated by bilateral infusion of the neurotoxin dermorphin-saporin (DERM-SAP; 17 ng/µl) into the striatum. Animals were allowed to recover for eight days following the infusion, and then were given daily injections of COC (25mg/kg) or saline for one week, followed by a weeklong drug-free period. Animals were then given a challenge dose of saline or COC, observed for 2h in activity chambers and sacrificed. The number of mu-labeled patches in the striatum were reduced by DERM-SAP pretreatment. In COC-treated animals DERM-SAP pretreatment significantly reduced the immobilization and intensity of stereotypy but increased locomotor activity. DERM-SAP pretreatment attenuated COC-induced c-Fos expression in the patch compartment, while enhancing COC-induced c-Fos expression in the matrix compartment. These data indicate that the patch compartment contributes to repetitive behavior and suggests that alterations in activity in the patch vs matrix compartments may underlie to this phenomenon.

Asunto(s)

Cocaína/administración & dosificación , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/lesiones , Inhibidores de Captación de Dopamina/administración & dosificación , Conducta Estereotipada/efectos de los fármacos , Analgésicos Opioides/toxicidad , Análisis de Varianza , Animales , Calbindinas/metabolismo , Cuerpo Estriado/metabolismo , Masculino , Péptidos Opioides/toxicidad , Compuestos Organometálicos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Opioides mu/metabolismo , Saponinas/toxicidad , Conducta Estereotipada/fisiología , Factores de Tiempo

RESUMEN

INTRODUCTION: Methadone substitution is claimed to be the most effective way of pharmacological management of human immunodeficiency virus (HIV) positive patients addicted to opioids. Possible and clinically the most relevant drug interactions are those between methadone and antiretroviral agents [13,18,25,32]. HIV causes cognitive impairment by infiltrating the central nervous system (CNS) in the initial phase of infection. The consequence of this is damage to the hippocampus, caudate nucleus, and basal ganglia [2,26]. METHODS: Eighty-six patients from the substitution program group were examined. The trial was conducted twice: before and about 1.5 hours after the administration of a therapeutic dose of methadone. The antisaccades task (AT) and latency task (LT) were performed using a saccadometer diagnostic system. RESULTS: The statistical analysis showed that the mean duration of latency measured by AT in HIV(-) and HIV(+) subjects after the administration of a therapeutic dose of methadone was significantly increased (p=0.03 HIV(-); p=0.04 HIV(+)). There was a statistically significant increase in the mean latency after the administration of methadone in HIV(+) subjects when compared to the control group measured by LT (p=0.03). CONCLUSION: The statistical analysis confirms the change in the saccadic refixation parameters in patients addicted to opioids. Methadone influences saccadic dynamic parameters less in HIV(+) than in HIV(-) drug users. Oculomotor disturbances are probably related to the neurotropic effects of HIV leading to damage of the striatum, which plays an important role in psychomotor functions.

Asunto(s)

Antirretrovirales/efectos adversos , Enfermedades de los Ganglios Basales/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Hipocampo/lesiones , Metadona/efectos adversos , Movimientos Sacádicos/efectos de los fármacos , Ganglios Basales/lesiones , Cuerpo Estriado/lesiones , Interacciones Farmacológicas , Humanos

RESUMEN

In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this region, but not of regions in the posterolateral striato-pallidum, abolish the attraction of female mice for male chemosignals, without affecting significantly their preference for a different natural reward (a sucrose solution). These results show that, at least in female mice, the integrity of the anterior aspect of the medioventral striato-pallidum, comprising a portion of the olfactory tubercle and associated islands of Calleja, is necessary for the attraction for male chemosignals. We suggest that this region contributes to the processing of the hedonic properties of biologically significant odorants.

Asunto(s)

Cuerpo Estriado/fisiología , Globo Pálido/fisiología , Vías Olfatorias/fisiología , Atractivos Sexuales , Conducta Sexual Animal/fisiología , Análisis de Varianza , Animales , Cuerpo Estriado/lesiones , Femenino , Globo Pálido/lesiones , Masculino , Ratones , Actividad Motora/fisiología , Recompensa

RESUMEN

Reactive astrogliosis, a feature of neuro-inflammation is induced by a number of endogenous mediators including cytokines. Despite interleukin-1 beta (IL-1ß) stands out as the major inducer of this process, the underlying mechanism and its role on neuronal viability remain elusive. We investigated in human astrocytoma cells and the rat brain striatum, the role of the nuclear factor-kB (NF-kB) intracellular Ca(2+) concentration ([Ca(2+)]i) calmodulin (CaM) and extracellular regulated mitogen-activated protein kinases (ERK1/2) in IL-1ß-induced expression of glial fibrillary acidic protein (GFAP) and neuronal apoptosis associated to a brain trauma. Cell data showed that IL-1ß (1 ng/ml) increased NF-kB, pERK1/2 and GFAP expression. Nevertheless, further increase in IL-1ß levels reversed progressively these responses. Preventing ERK1/2 activation with 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthiol]-butadiene antagonized IL-1ß-induced GFAP expression while inhibiting selectively nuclear translocation of NF-kB with caffeic-acid phenethyl-ester down-regulated both ERK1/2 and GFAP expression induced by IL-1ß. The GFAP response was also prevented by antagonizing selectively increase in [Ca(2+)]i, CaM activity or inducible nitric oxide synthase expression with respectively ryanodine plus 2-aminoethoxydiphenyl-borate, N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide hydrochloride and N-[(3-(aminomethyl)-phenyl]methyl]-ethanimidamide dihydrochloride. Data in vivo supported these findings and showed that GFAP expression induced by IL-1ß (50 ng/ml) correlated with attenuated glial scar formation and reduced neuronal apoptosis. Our data identified the NF-kB/Ca(2+)-CaM/ERK signaling pathway as a novel in vivo key regulator of IL-1ß-induced astrogliosis which may represent a potential target in neurodegeneration.

Asunto(s)

Apoptosis/fisiología , Astrocitos/metabolismo , Interleucina-1beta/metabolismo , Degeneración Nerviosa/metabolismo , Neuronas/metabolismo , Transducción de Señal/fisiología , Animales , Western Blotting , Calcio/metabolismo , Señalización del Calcio , Calmodulina/metabolismo , Línea Celular Tumoral , Cuerpo Estriado/lesiones , Cuerpo Estriado/metabolismo , Proteína Ácida Fibrilar de la Glía/biosíntesis , Humanos , Inmunohistoquímica , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley

RESUMEN

Decision making requires an actor to not only steer behavior toward specific goals but also determine the optimal vigor of performance. Current research and models have largely focused on the former problem of how actions are directed while overlooking the latter problem of how they are energized. Here we designed a self-paced decision-making paradigm, which showed that rats' performance vigor globally fluctuates with the net value of their options, suggesting that they maintain long-term estimates of the value of their current state. Lesions of the dorsomedial striatum (DMS) and, to a lesser degree, in the ventral striatum impaired such state-dependent modulation of vigor, rendering vigor to depend more exclusively on the outcomes of immediately preceding trials. The lesions, however, spared choice biases. Neuronal recordings showed that the DMS is enriched in net value-coding neurons. In sum, the DMS encodes one's net expected return, which drives the general motivation to perform.

Asunto(s)

Condicionamiento Operante/fisiología , Cuerpo Estriado/fisiología , Toma de Decisiones/fisiología , Motivación/fisiología , Potenciales de Acción/fisiología , Animales , Simulación por Computador , Cuerpo Estriado/citología , Cuerpo Estriado/lesiones , Discriminación en Psicología/fisiología , Modelos Logísticos , Masculino , Modelos Neurológicos , Neuronas/fisiología , Odorantes , Psicometría , Ratas , Ratas Long-Evans , Tiempo de Reacción , Análisis de Regresión , Recompensa

RESUMEN

Traumatic brain injury (TBI) causes significant mortality in most developing countries worldwide. At present, it is imperative to identify a treatment to address the devastating post-TBI consequences. Therefore, the present study has been performed to assess the specific effect of immediate exposure to normabaric hyperoxia (NBO) after fluid percussion injury (FPI) in the striatum of mice. To execute FPI, mice were anesthetised and sorted into (i) a TBI group, (ii) a sham group without injury and (iii) a TBI group treated with immediate exposure to NBO for 3 h. Afterwards, brains were harvested for morphological assessment. The results revealed no changes in morphological and neuronal damage in the sham group as compared to the TBI group. Conversely, the TBI group showed severe morphological changes as well as neuronal damage as compared to the TBI group exposed to NBO for 3 h. Interestingly, our findings also suggested that NBO treatment could diminish the neuronal damage in the striatum of mice after FPI. Neuronal damage was evaluated at different points of injury and the neighbouring areas using morphology, neuronal apoptotic cell death and pan-neuronal markers to determine the complete neuronal structure. In conclusion, immediate exposure to NBO following FPI could be a potential therapeutic approach to reduce neuronal damage in the TBI model.

Asunto(s)

Lesiones Encefálicas/tratamiento farmacológico , Cuerpo Estriado/efectos de los fármacos , Hiperoxia/metabolismo , Neuronas/efectos de los fármacos , Oxígeno/farmacología , Animales , Apoptosis/efectos de los fármacos , Barotrauma , Biomarcadores/metabolismo , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Supervivencia Celular/efectos de los fármacos , Cuerpo Estriado/lesiones , Cuerpo Estriado/metabolismo , Expresión Génica/efectos de los fármacos , Histocitoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Neuronas/patología , Técnicas Estereotáxicas