RESUMEN
Cognitive abilities play an important role for migratory birds that are briefly visiting a variety of unfamiliar stop-over habitats. Here, we compared cognitive abilities-linked behaviour (escape from an experimental cage) between two long-distant migrants differing in stop-over ecology, Sedge Warbler (Acrocephalus schoenobaenus; not territorial, searching for locally superabundant food) and Reed Warbler (A. scirpaceus; territorial, foraging on a common prey) during the autumn migration. After two minutes of acclimatization in the cage, we remotely opened the cage door and recorded the bird's reaction. We measured latency that individuals needed to escape from a cage. Sedge warblers were 1.61 times more likely to escape from the cage than Reed Warblers. Sedge warblers generally escaped earlier after the door was opened and were 1.79 times more likely to escape at any given time than Reed Warblers. We interpret the prevalence of non-escaped individuals as a general feature of migratory birds. In contrast to resident species, they are more likely to enter an unfamiliar environment, but they are less explorative. We attributed inter-species differences in escape latency to species-specific autumn stop-over refuelling strategies in the context of specialist-generalist foraging. Our study provides ecological insight into the cognitive abilities-linked behaviour of wild animals.
RESUMEN
Recent interest in the lasting effects of early-life stress has expanded to include effects on cognitive performance. An increase in circulating glucocorticoids is induced by stress exposure and glucocorticoid effects on the hippocampus likely underlie many of the cognitive consequences. Here we review studies showing that corticosterone administered to young rats at the conclusion of the stress-hyporesponsiveness period affects later performance in hippocampally-mediated trace eyeblink conditioning. The nature and even direction of these effects varies with the elevation patterns (level, duration, temporal fluctuation) achieved by different administration methods. We present new time course data indicating that constant glucocorticoid elevations generally corresponded with hippocampus-mediated learning deficits, whereas acute, cyclical elevations corresponded with improved initial acquisition. Sensitivity was greater for males than for females. Further, changes in hippocampal neurogenesis paralleled some but not all effects. The findings demonstrate that specific patterns of glucocorticoid elevation produced by different drug administration procedures can have markedly different, sex-specific consequences on basic cognitive performance and underlying hippocampal physiology. Implications of these findings for glucocorticoid medications prescribed in childhood are discussed.
Asunto(s)
Condicionamiento Palpebral/fisiología , Corticosterona/fisiología , Hipocampo/fisiología , Animales , Cognición/fisiología , Corticosterona/administración & dosificación , Corticosterona/sangre , Humanos , Neurogénesis , Ratas , Caracteres SexualesRESUMEN
Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75-95% synaptic losses) and on the proximal 100 µm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.
Asunto(s)
Neuronas Motoras/fisiología , Regeneración Nerviosa/fisiología , Terminales Presinápticos/metabolismo , Propiocepción/fisiología , Nervio Tibial/fisiopatología , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Animales , Axones/metabolismo , Axones/fisiología , Axotomía , Biotina/análogos & derivados , Biotina/metabolismo , Dendritas/metabolismo , Dendritas/patología , Electromiografía , Potenciales Postsinápticos Excitadores/fisiología , Neuronas Motoras/patología , Músculo Esquelético/inervación , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Neuronas Aferentes/fisiología , Terminales Presinápticos/patología , Ratas , Ratas Wistar , Recuperación de la Función/fisiología , Reflejo de Estiramiento/fisiología , Nervio Tibial/lesiones , Nervio Tibial/patología , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/fisiologíaRESUMEN
OBJECTIVE: Fluorodeoxyglucose (FDG)-positron emission tomographic (PET) imaging plays an important role in the evaluation of intractable epilepsy. The metabolic defect has proven utility in the lateralization of temporal lobe epilepsy. However, the role of FDG-PET imaging in the localization of a seizure focus within the temporal lobe is uncertain. We evaluated FDG-PET imaging for the capability to localize a temporal seizure focus within the mesial structures. METHODS: Twenty-eight patients who underwent selective amygdalohippocampectomy for intractable temporal lobe epilepsy were studied. Patients were divided into 2 groups: those who were free of seizures (FS) and those with persisting seizures postoperatively. FS patients were defined by having mesial temporal lobe epilepsy (MTLE). Preoperative FDG-PET activity was evaluated in temporal lobe structures and contrasted with magnetic resonance imaging (MRI) for usefulness in identifying MTLE in an individual. RESULTS: Pathology of the hippocampus revealed mesial temporal sclerosis in all but 1 patient. Qualitative visual inspection of the MRI scan was not reliable in the identification of MTLE (P = 0.15). MRI volumetry found smaller mesial temporal structures (P = 0.04) in FS patients. Mesial temporal metabolic activity was reduced in the FS group (hippocampus, P = 0.001). However, a combination of imaging modalities was found to be the best predictor of MTLE. PET imaging plus MRI qualitative inspection identified all patients with and without MTLE correctly and was superior to MRI alone (P = 0.01 and P = 0.02, respectively). CONCLUSION: MRI volumetry and PET imaging were comparable (P = 0.73) and able to identify MTLE in most patients, but a combination of PET imaging and MRI visual inspection was superior in the recognition of MTLE.
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Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Epilepsia del Lóbulo Temporal/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Elimination of hydrogen sulfide from glutathione (GSH) converts a well known cellular nucleophile to an electrophilic species, gamma-glutamyldehydroalanylglycine (EdAG). We have found that a sulfonium metabolite formed from GSH and busulfan undergoes a facile beta-elimination reaction to give EdAG, which is an alpha,beta-unsaturated dehydroalanyl analog of GSH. EdAG was identified as a metabolite of busulfan in a human liver cytosol fraction. EdAG condenses with GSH in a Michael addition reaction to produce a lanthionine thioether [(2-amino-5-[[3-[2-[[4-amino-5-hydroxy-5-oxopentanoyl]amino]-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid); GSG], which is a nonreducible analog of glutathione disulfide. EdAG was less cytotoxic than busulfan to C6 rat glioma cells. GSH and EdAG were equally effective in displacing a glutathione S-transferase (GST) isozyme (human GSTA1-1) from a GSH-agarose column. The finding of an electrophilic metabolite of GSH suggests that alteration of cellular GSH concentrations, irreversible nonreducible glutathionylation of proteins, and interference with GST function may contribute to the toxicity of busulfan.
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Busulfano/metabolismo , Glutatión Transferasa/metabolismo , Glutatión/análogos & derivados , Glutatión/metabolismo , Alanina/análogos & derivados , Animales , Antineoplásicos Alquilantes , Busulfano/farmacología , Línea Celular Tumoral , Glioma/tratamiento farmacológico , Disulfuro de Glutatión/análogos & derivados , Humanos , Hígado , RatasRESUMEN
Although cognitive dysfunction manifested by severe memory and attention deficits has been reported in up to 70% of cancer patients undergoing chemotherapy, the mechanisms of this serious side effect have not been defined. In particular, it has not been decisively resolved whether the dysfunction is attributable to the chemotherapy or to the malignancy itself. In the present study we tested whether cognitive dysfunction can be induced in an experimental setting by the administration of commonly used chemotherapeutics to rats. Female 10 month old Sprague-Dawley rats were injected intraperitoneally with a combination of 2.5 mg/kg of adriamycin (ADR) and 25 mg/kg of cytoxan (CTX). A total of four doses were given at weekly intervals. The control group was treated with saline only. No mortality and no apparent morbidity were observed in either group. However, the chemotherapeutic treatment severely impaired memory function of rats as measured by a passive avoidance test. This memory deficiency was fully prevented by the administration of an antioxidant, N-acetyl cysteine (NAC) injected subcutaneously three times a week at 200 mg/kg in the course of chemotherapeutic treatment. These results indicate that chemotherapeutic agents alone, i.e., in the absence of malignancy, damage the brain resulting in memory dysfunction. Moreover, the results strongly indicate that the damaging effect is mediated by oxidative stress, as memory dysfunction is preventable by the co-administration of NAC.
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Antineoplásicos/toxicidad , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/psicología , Animales , Antibióticos Antineoplásicos/toxicidad , Antineoplásicos Alquilantes/toxicidad , Antioxidantes/uso terapéutico , Reacción de Prevención/efectos de los fármacos , Trastornos del Conocimiento/prevención & control , Ciclofosfamida/toxicidad , Doxorrubicina/toxicidad , Femenino , Memoria a Corto Plazo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECT: The pli de passage moyen (PPM) is an omega-shaped cortical landmark bulging into the central sulcus. There has been considerable interest in the PPM given that hand motor and sensory tasks have been found on functional magnetic resonance (fMR) imaging to activate the structure. Note, however, that the cortical function subserved by the PPM is not completely understood. Finger and thumb function are somatotopically organized over the central area and encompass a larger cortical surface than the anatomical PPM. Therefore, a sensory or motor hand area within the PPM would be redundant with the somatotopically organized digit function in the primary sensorimotor cortex. In this study the authors aimed to clarify the function subserved by the PPM and further evaluate hand area function in the primary sensorimotor cortex. METHODS: To further elucidate the function subserved by the PPM, patients underwent cortical stimulation in the region of the PPM as well as fMR imaging-demonstrated activation of the hand area. Two separate analytical methods were used to correlate hand area functional imaging with whole-hand sensory and motor responses induced by cortical stimulation. RESULTS: A relationship of the anatomical PPM with cortical stimulation responses as well as hand fMR imaging activation was observed. CONCLUSIONS: A strong relationship was identified between the PPM, whole-hand sensory and motor stimulation responses, and fMR imaging hand activation. Whole-hand motor and whole-hand sensory cortical regions were identified in the primary sensorimotor cortex. It was localized to the PPM and exists in addition to the somatotopically organized finger and thumb sensory and motor areas.
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Encefalopatías/fisiopatología , Mapeo Encefálico/métodos , Corteza Cerebral/fisiopatología , Mano/fisiología , Desempeño Psicomotor/fisiología , Tacto/fisiología , Adulto , Anciano , Encefalopatías/patología , Encefalopatías/psicología , Corteza Cerebral/patología , Estudios de Cohortes , Señales (Psicología) , Estimulación Eléctrica , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Toll-like receptors (TLRs) are sentinels of innate immunity that recognize pathogenic molecules and trigger inflammatory response. Because inflammatory mediators are detrimental to the host, the TLR response is regulated by feedback inhibition. Statins, the inhibitors of isoprenoid biosynthesis, have been shown to be potent modulators of TLR activity, and this modulation may provide insight regarding mechanisms of the feedback inhibition. In the present study, we examined feedback mechanisms that regulate TLR4 activity in astrocytes using statins to perturb postligational signaling. Astrocytic cultures established from newborn rat brains were exposed to lipopolysaccharide (LPS), the ligand for TLR4. The up-regulation of expression of genes encoding interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNFalpha) was determined by real-time RT-PCR. Pretreatment of the cells with either atorvastatin or simvastatin enhanced the LPS-induced up-regulation of cytokine gene expression. The most profound enhancement of approximately 17-fold was observed for the Il-6 gene. The enhancements for the Tnfa and Il-1b genes were approximately 5- and 3.5-fold, respectively. Mevalonate fully reversed the effects of statins, indicating that these drugs act through the inhibition of isoprenoid synthesis. The inhibition of protein geranylgeranylation, but not protein farnesylation, mimicked the effects of statins, strongly indicating that the enhancement is mediated by the Rho proteins. In support of this notion, pretreatment of cells with toxin B, a specific inhibitor of the Rho proteins, also enhanced LPS-triggered up-regulation of the cytokine genes. These results indicate that the Rho proteins are involved in the activation of negative feedback inhibition of TLR4 signaling in astrocytes.
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Astrocitos/metabolismo , Citocinas/genética , Expresión Génica/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Receptor Toll-Like 4/metabolismo , Animales , Astrocitos/efectos de los fármacos , Proteínas Bacterianas/farmacología , Toxinas Bacterianas/farmacología , Células Cultivadas , Retroalimentación Fisiológica , Lipopolisacáridos/farmacología , Ácido Mevalónico/farmacología , Prenilación de Proteína/fisiología , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba , Proteínas de Unión al GTP rho/antagonistas & inhibidores , Proteínas de Unión al GTP rho/metabolismoRESUMEN
Toll-like receptors (TLRs) are sentinels of the innate immune system that recognize an array of exogenous and endogenous pathogenic molecules. The ligation of the receptors triggers inflammatory response necessary for pathogen elimination and for the healing process. In the present study we examined inflammatory response of astrocytes elicited by the ligation of TLR3 and TLR4. Astrocytic cultures established from newborn rat brains were exposed to double stranded RNA (dsRNA) and lipopolysaccharide (LPS), the ligands for TLR3 and TLR4, respectively. The expression of cytokine genes was determined by RNase protection assay, and the generation of nitric oxide (NO) was measured by Griess technique. Both ligands upregulated the expression of several cytokines (i.e., IL-1alpha, IL-1beta, IL-6, TNFalpha, GM-CSF, LTbeta, and TGFbeta3) and downregulated the expression of MIF, but have no effect on the expression of IL-2, IL-3, IL-4, IL-5, IL-10, TGFbeta1, TGFbeta2, TNFbeta, and IFNgamma. Although dsRNA upregulated the expression of IFNbeta, LPS did not indicating that the TRIF-dependent branch of TLR4 signaling is inactive in astrocytes. Proinflammatory response as seen from upregulated cytokine expression and NO generation reached a peak within the first day of exposure, and was subsequently abrogated. The cells also became refractory to subsequent stimulation by the ligands indicating the existence of negative feedback mechanisms that control proinflammatory response in astrocytes.
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Astrocitos/metabolismo , Inflamación/patología , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Animales Recién Nacidos , Astrocitos/efectos de los fármacos , Encéfalo/citología , Células Cultivadas , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Ensayo de Cambio de Movilidad Electroforética , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Inflamación/inducido químicamente , Ligandos , Lipopolisacáridos/farmacología , Óxido Nítrico/metabolismo , ARN Bicatenario/farmacología , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Tiempo , Receptor Toll-Like 3/genética , Receptor Toll-Like 4/genéticaRESUMEN
The amygdala plays a critical role in generating the emotion of fear, and alterations in amygdala fear processing are thought to underlie the acquisition and maintenance of anxiety disorders. The prenatally stressed (PS) rat displays hormonal, behavioral and brain anatomical similarities to anxious humans and is useful to study the neurobiological underpinnings of pathological anxiety. We studied PS and control male rats at postnatal days 7 (P7), P25, P45 and P60. Using unbiased stereological analyses we examined the volumes, anterior-posterior lengths and total numbers of neurons and glia of the basolateral (BL), central (Ce) and lateral (La) amygdalar nuclei. We found prenatal stress-associated differences in the developmental trajectories of each nucleus. These were apparent in some measures as early as P7, most extensive at P25 and resolved by P45, at least as seen by Nissl staining. These changes were not a result of differential brain growth. This early divergence in developmental trajectories seen here may be the harbinger of PS rat amygdalas that ultimately function very differently in adulthood.
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Amígdala del Cerebelo/patología , Efectos Tardíos de la Exposición Prenatal , Estrés Psicológico/patología , Amígdala del Cerebelo/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Recuento de Células , Femenino , Neuroglía/patología , Neuronas/patología , Embarazo , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Anxiety disorders in humans have been associated with chronic activation of the hypothalamic-pituitary-adrenal axis and changes in the volume of the amygdala. Interest in the etiology of anxiety disorders has led us and others to investigate the effects of prenatal stress on the brain development of adult male rat offspring. Prenatally stressed rats represent a promising animal model for anxiety disorders in that they have already been characterized as having both upregulated corticotropin-releasing factor (CRF) brain biochemistry and altered, more fearful, behaviors. Consistent with this, there is now evidence that prenatal stress also has an impact on the development of CRFergic neurons in the hypothalamic paraventricular nucleus and neurogenesis in the hippocampus. At this time, little information about the impact of prenatal stress on amygdala anatomy has been presented. Here we asked whether prenatal stress also has an impact on the development of the amygdala, because this structure plays a direct role in the emotions of anxiety and fear. Stereological measures of well-defined subregions of amydgdaloid nuclei revealed significantly expanded dimensions of the lateral nucleus in prenatally stressed offspring, due, in part, to more neurons and glia. These data may have direct import for the effect of adverse early life experiences and the etiology of anxiety disorders in humans. They also imply that early experiences may not be "grown out of" with development; in fact, the opposite might be true-adverse early life experiences may set developmental events into motion in the brain that last a lifetime.