RESUMEN
Several partly overlapping diseases have Parkinsonism as a symptom and tools that may differentiate between these disorders would be helpful. The authors evaluated the discriminating properties of the objective automated posturo-locomotor-manual (PLM) L-DOPA test in regard to health, and the movement disorders Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). A PLM test-retest procedure was performed in healthy controls (n = 37) and results were compared with PLM L-DOPA tests performed by 132 patients with Parkinsonism in intermediate to advanced stages (56 PD, 53 MSA, 23 PSP). The movement time (MT) for the standardized movement and its different components was measured. The discriminating abilities of individual, or combinations of, test variables were determined by forward stepwise multiple logistic regression and evaluated with receiver-operating characteristic (ROC) analysis. Each PLM variable separated healthy persons from patients with Parkinsonism before administration of L-DOPA (area under the curve (AUC) = 0.94-0.99, p < .001 for any separate variable). A combination of (MToff - MTon)/MToff and MTon had the highest ability to separate patients with PD from patients with atypical Parkinsonism (area under the curve = 0.91, p < .001). The PLM test discriminates between healthy controls and patients with Parkinsonism, and between patients with Parkinson's disease and patients with atypical Parkinsonism.
Asunto(s)
Movimiento/fisiología , Trastornos Parkinsonianos/fisiopatología , Anciano , Antiparkinsonianos/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Levodopa/uso terapéutico , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/diagnóstico , Atrofia de Múltiples Sistemas/fisiopatología , Trastornos Parkinsonianos/diagnóstico , Postura/fisiología , Curva ROC , Reproducibilidad de los Resultados , Parálisis Supranuclear Progresiva/diagnóstico , Parálisis Supranuclear Progresiva/fisiopatologíaRESUMEN
After cancer and cardio-vascular disease, stroke is the third greatest cause of death worldwide. Given the limitations of the current imaging technologies used for stroke diagnosis, the need for portable non-invasive and less expensive diagnostic tools is crucial. Previous studies have suggested that electrical bioimpedance (EBI) measurements from the head might contain useful clinical information related to changes produced in the cerebral tissue after the onset of stroke. In this study, we recorded 720 EBI Spectroscopy (EBIS) measurements from two different head regions of 18 hemispheres of nine subjects. Three of these subjects had suffered a unilateral haemorrhagic stroke. A number of features based on structural and intrinsic frequency-dependent properties of the cerebral tissue were extracted. These features were then fed into a classification tree. The results show that a full classification of damaged and undamaged cerebral tissue was achieved after three hierarchical classification steps. Lastly, the performance of the classification tree was assessed using Leave-One-Out Cross Validation (LOO-CV). Despite the fact that the results of this study are limited to a small database, and the observations obtained must be verified further with a larger cohort of patients, these findings confirm that EBI measurements contain useful information for assessing on the health of brain tissue after stroke and supports the hypothesis that classification features based on Cole parameters, spectral information and the geometry of EBIS measurements are useful to differentiate between healthy and stroke damaged brain tissue.
Asunto(s)
Diagnóstico por Computador/instrumentación , Diagnóstico por Computador/métodos , Espectroscopía Dieléctrica/instrumentación , Espectroscopía Dieléctrica/métodos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Adulto , Algoritmos , Inteligencia Artificial , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Objective methods for quantifying patients' movement capacity would be useful in evaluating progression and interventions in neurodegenerative diseases. The Posturo-Locomotor-Manual (PLM) test is a standardized automated movement test developed to measure hypokinetic movements in patients with Parkinsonism. Our hypotheses were that the PLM movement time (MT) correlates with the Unified Parkinson's disease rating scale (UPDRS III) motor section, and that the components of the PLM test correlate with the corresponding constructed domains of UPDRS III. We also evaluated the coherence between the results of the two assessment methods after a test dose of levodopa (l-DOPA). We assessed motor function using the PLM method and UPDRS III in parallel, in the absence of medication and after administration of 200 mg l-DOPA, in 73 patients with moderate to advanced Parkinsonism: 47 with Parkinson's disease (PD), 17 with multiple system atrophy (MSA), and 9 with progressive supranuclear palsy (PSP). There was a fair correlation between the two assessment tools in the PD patients but not in the MSA or PSP patients. In the full dataset, there was a fair to good correlation between UPDRS III and the PLM MT. At group level, the UPDRS III l-DOPA test differentiated PD from MSA/PSP, whereas the PLM l-DOPA test differentiated between all three diagnoses.
RESUMEN
Vagus nerve stimulation (VNS), used in the treatment of epilepsy, was approved recently for treatment-resistant depression. The mechanisms of action of the VNS anti-depressive effects are not yet fully elucidated. Modulation of hippocampal neurogenesis has been proposed as an important factor in depression pathogenesis. We evaluated the effects of VNS on hippocampal progenitor turnover in the adult rat brain. Rats receiving VNS at the output current of 0.75 mA VNS for 2 days showed a significant 50% increase in dentate gyrus BrdU-incorporation consistent with an increase in progenitor proliferation. Output currents of 0.5 or 1.5 mA yielded non-significant trends for increased BrdU-labeling indicating an inverted U-shaped proliferative dose response to VNS as previously reported for other VNS-induced effects. Specific analysis for progenitor survival revealed no effects by VNS on dentate gyrus BrdU-labeling. These results suggest that VNS induced an increase in the number of available progenitor cells in the adult rat dentate gyrus by a mechanism presumably involving increased progenitor proliferation.
Asunto(s)
Giro Dentado/citología , Depresión/terapia , Terapia por Estimulación Eléctrica , Células Madre/fisiología , Nervio Vago/fisiología , Animales , División Celular/fisiología , Giro Dentado/fisiología , Masculino , Plasticidad Neuronal/fisiología , Neuronas/citología , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Nicho de Células Madre/fisiología , Células Madre/citologíaRESUMEN
The rapid rise in the use of mobile communications has raised concerns about health issues related to low-level microwave radiation. The head and brain are usually the most exposed targets in mobile phone users. In the brain, two types of glial cells, the astroglial and the microglial cells, are interesting in the context of biological effects from microwave exposure. These cells are widely distributed in the brain and are directly involved in the response to brain damage as well as in the development of brain cancer. The aim of the present study was to investigate whether 900 MHz radiation could affect these two different glial cell types in culture by studying markers for damage-related processes in the cells. Primary cultures enriched in astroglial cells were exposed to 900 MHz microwave radiation in a temperature-controlled exposure system at specific absorption rates (SARs) of 3 W/kg GSM modulated wave (mw) for 4, 8 and 24 h or 27 W/kg continuous wave (cw) for 24 h, and the release into the extracellular medium of the two pro-inflammatory cytokines interleukin 6 (Il6) and tumor necrosis factor-alpha (Tnfa) was analyzed. In addition, levels of the astroglial cell-specific reactive marker glial fibrillary acidic protein (Gfap), whose expression dynamics is different from that of cytokines, were measured in astroglial cultures and in astroglial cell-conditioned cell culture medium at SARs of 27 and 54 W/kg (cw) for 4 or 24 h. No significant differences could be detected for any of the parameters studied at any time and for any of the radiation characteristics. Total protein levels remained constant during the experiments. Microglial cell cultures were exposed to 900 MHz radiation at an SAR of 3 W/kg (mw) for 8 h, and I16, Tnfa, total protein and the microglial reactivity marker ED-1 (a macrophage activation antigen) were measured. No significant differences were found. The morphology of the cultured astroglial cells and microglia was studied and appeared to be unaffected by microwave irradiation. Thus this study does not provide evidence for any effect of the microwave radiation used on damage-related factors in glial cells in culture.
Asunto(s)
Astrocitos/efectos de la radiación , Encéfalo/citología , Microglía/efectos de la radiación , Microondas , Animales , Astrocitos/citología , Astrocitos/metabolismo , Forma de la Célula/efectos de la radiación , Células Cultivadas , Ectodisplasinas , Interleucina-6/metabolismo , Proteínas de la Membrana/metabolismo , Microglía/citología , Microglía/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Factores de Necrosis Tumoral/metabolismoRESUMEN
It has previously been suggested that exogenous growth hormone (GH) affect quality of life and higher brain functions through the endogenous opioid system. Recently, we showed that GH down-regulate 72 and 48 kDa delta opioid receptor (DOR) proteins in the adult rat cerebral cortex and cerebellum. In the present study, we found that an antiserum raised against the N-terminus of the DOR also recognizes a 36 kDa protein, not recognized by a C-terminus-directed antiserum. We aimed to investigate the identity of the 72, 48 and 36 kDa proteins and to further study the effects of GH on their expression in different brain regions. The expression was studied in hypophysectomized (Hx) and untreated normal female rats. One subgroup of Hx rats received GH as a daily subcutaneous injection for 19 days. Our data show that treatment with GH in Hx rats normalized the expression of the 72 kDa protein in the cerebral cortex, whereas no significant effect were observed for the 48 or 36 kDa proteins. However, GH significantly reduced the ratio between the 72 and 36 kDa proteins in different brain regions of Hx rats. Our data suggest that GH reduces the levels of a 72 kDa DOR that likely represents a dimeric form of a 36 kDa DOR post-translationally truncated at the C-terminus, and that altered receptor dimerization may be involved in GH induced effects in the central nervous system.
Asunto(s)
Encéfalo/metabolismo , Hormona del Crecimiento/farmacología , Isoformas de Proteínas/biosíntesis , Receptores Opioides delta/biosíntesis , Animales , Western Blotting , Encéfalo/efectos de los fármacos , Femenino , Hormona del Crecimiento/metabolismo , Hipofisectomía , Isoformas de Proteínas/química , Isoformas de Proteínas/efectos de los fármacos , Procesamiento Proteico-Postraduccional , Ratas , Receptores Opioides delta/química , Receptores Opioides delta/efectos de los fármacosRESUMEN
Previous work has shown that voluntary running increases cell proliferation and neurogenesis in the dentate gyrus of the adult hippocampus. Here we report that long-term running for 24 days results in a down-regulation of hippocampal progenitor proliferation to one-half the level of nonrunning controls compared with a fivefold increase in progenitor proliferation seen after 9 days of voluntary running (short-term running). The negative effects seen on proliferation after 24 days of running were prevented by restricting daily running distances (by 30-50%) during 24 days. Long-term running for 24 days increases the response of the hypothalamic-pituitary-adrenal axis, with an increase in adrenal gland weight and increased plasma corticosterone levels, as well as decreased thymus weight, indicating a stress response as a possible mediator of decreased progenitor proliferation. Furthermore, the negative effects seen on the observed stress response after 24 days of running were prevented by restricting daily running distance. Short-term running did not alter these stress parameters compared with nonrunning controls. However, it increased phosphorylated cyclic AMP response element binding protein (pCREB) in the dentate gyrus, an increase that was not seen in nonrunning controls or after 24 days of running. Taken together, these data suggest that voluntary running does not always enhance proliferation and that the decrease in progenitor proliferation seen in long-term running is possibly mediated by mechanisms involving a stress response in the animal. However, a moderate level of long-term running was able to prevent the negative stress-related changes seen in unrestricted long-term running.
Asunto(s)
Proliferación Celular , Hipocampo/citología , Inhibición Psicológica , Condicionamiento Físico Animal/fisiología , Carrera/fisiología , Células Madre/fisiología , Glándulas Suprarrenales/fisiología , Análisis de Varianza , Animales , Animales Recién Nacidos , Conducta Animal , Bromodesoxiuridina/metabolismo , Recuento de Células/métodos , Corticosterona/sangre , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Femenino , Hipocampo/fisiología , Inmunohistoquímica/métodos , Fosforilación , Distribución Aleatoria , Ratas , Ratas Endogámicas SHR/fisiología , Timo/fisiología , Factores de TiempoRESUMEN
Voluntary running in mice and forced treadmill running in rats have been shown to increase the amount of proliferating cells in the hippocampus. Little is known as yet about the mechanisms involved in these processes. It is well known that the endogenous opioid system is affected during running and other forms of physical exercise. In this study, we evaluated the involvement of the endogenous opioids in the regulation of hippocampal proliferation in non-running and voluntary running rats. Nine days of wheel running was compared with non-running in spontaneously hypertensive rats (SHR), a rat strain known to run voluntarily. On the last 2 days of the experimental period all rats received two daily injections of the opioid receptor antagonists naltrexone or naltrindole together with injections of bromodeoxyuridine to label dividing cells. Brain sections from the running rats showed approximately a five-fold increase in newly generated cells in the hippocampus, and this increase was partly reduced by naltrexone but not by naltrindole. By contrast, both naltrexone and naltrindole increased hippocampal proliferation in non-running rats. In non-running rats the administration of naltrexone decreased corticosterone levels and adrenal gland weights, whereas no significant effects on these parameters could be detected for naltrindole. However, adrenal gland weights were increased in naltrexone- but not in naltrindole-administered running rats. In addition, in voluntary running rats there was a three-fold increase in the hippocampal levels of Met-enkephalin-Arg-Phe compared with non-runners, indicating an increase in opioid activity in the hippocampus during running. These data suggest an involvement of endogenous opioids in the regulation of hippocampal proliferation in non-running rats, probably through hypothalamic-pituitary-adrenal axis modulation. During voluntary running in SHR naltrexone altered hippocampal proliferation via as yet unknown mechanisms.
Asunto(s)
Encefalina Metionina/análogos & derivados , Hipocampo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/farmacología , Receptores Opioides/metabolismo , Carrera , Hormona Adrenocorticotrópica/sangre , Animales , Conducta Animal , Bromodesoxiuridina/metabolismo , División Celular/efectos de los fármacos , Corticosterona/sangre , Encefalina Metionina/metabolismo , Femenino , Hipocampo/patología , Hipocampo/fisiología , Actividad Motora/fisiología , Naltrexona/farmacología , Narcóticos/metabolismo , Condicionamiento Físico Animal , Radioinmunoensayo/métodos , Distribución Aleatoria , Ratas , Ratas Endogámicas SHR/metabolismo , betaendorfina/metabolismoRESUMEN
A comparative, computational study of the modeling of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) is presented using a human head model. The magnetic fields from a typical TMS coil of figure-eight type is modeled using the Biot-Savart law. The TMS coil is placed in a position used clinically for treatment of depression. Induced current densities and electric field distributions are calculated in the model using the impedance method. The calculations are made using driving currents and wave forms typical in the clinical setting. The obtained results are compared and contrasted with the corresponding ECT results. In the ECT case, a uniform current density is injected on one side of the head and extracted from the equal area on the opposite side of the head. The area of the injected currents corresponds to the electrode placement used in the clinic. The currents and electric fields, thus, produced within the model are computed using the same three-dimensional impedance method as used for the TMS case. The ECT calculations are made using currents and wave forms typical in the clinic. The electrical tissue properties are obtained from a 4-Cole-Cole model. The numerical results obtained are shown on a two-dimenaional cross section of the model. In this study, we find that the current densities and electric fields in the ECT case are stronger and deeper penetrating than the corresponding TMS quantities but both methods show biologically interesting current levels deep inside the brain.
Asunto(s)
Encéfalo/fisiología , Terapia Electroconvulsiva/métodos , Cabeza/fisiología , Magnetismo/uso terapéutico , Modelos Biológicos , Adulto , Anatomía Transversal , Simulación por Computador , Terapia por Estimulación Eléctrica/métodos , Campos Electromagnéticos , Humanos , Imagenología Tridimensional/métodos , Masculino , Radiometría/métodos , Terapia Asistida por Computador/métodos , Tomografía/métodosRESUMEN
Administration of opioid agonists or antagonists has been reported to regulate proliferation or survival of neural progenitors in vivo. Here we report that beta-endorphin and selective mu-opioid receptor (MOR) and delta-opioid receptor (DOR) agonists stimulate proliferation of isolated rat adult hippocampal progenitors (AHPs). The AHPs were found to express DORs and MORs, but not kappa-opioid receptors. Incubation with beta-endorphin for 48 h increased the number of AHPs found in mitosis, the total DNA content, and the expression of proliferating cell nuclear antigen. This proliferative effect from beta-endorphin on AHPs was antagonized by naloxone. The beta-endorphin-induced proliferation was mediated through phosphorylation of extracellular signal-regulated kinases 1 and 2 and dependent on phosphatidylinositol 3-kinase and both intra- and extracellular calcium. These data suggest a role for the opioid system in the regulation of proliferation in progenitors from the adult hippocampus.
Asunto(s)
Hipocampo/citología , Sistema de Señalización de MAP Quinasas/fisiología , Neuronas/citología , Células Madre/citología , betaendorfina/farmacología , Animales , Calcio/metabolismo , División Celular/efectos de los fármacos , Células Cultivadas , Femenino , Técnicas In Vitro , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Toxina del Pertussis/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Receptores Opioides delta/agonistas , Receptores Opioides kappa/agonistas , Receptores Opioides mu/agonistas , Células Madre/metabolismoRESUMEN
Opioids have previously been shown to affect proliferation and differentiation in various neural cell types. In the present study, cultured rat adult hippocampal progenitors (AHPs) were shown to release beta-endorphin. Membrane preparations of AHPs were found to bind [125I]beta-endorphin, and immunoreactivity for mu- and delta-opioid receptors (MORs and DORs), but not for kappa-opioid receptors (KORs), was found on cells in culture. Both DNA content and [3H]thymidine incorporation were reduced after a 48-h incubation with 100 microM naloxone, 10 micro m naltrindole or 10 microM beta-funaltrexamine, but not nor-binaltorphimine, suggesting proliferative actions of endogenous opioids against MORs and DORs on AHPs. Furthermore, analysis of gene and protein expression after incubation with MOR and DOR antagonists for 48 h using RT-PCR and Western blotting suggested decreased signalling through the mitogen-activated protein kinase (MAPK) pathway and lowered levels of genes and proteins that are important in cell cycling. Cultures were incubated with naloxone (10 or 100 microM) for 10 days to study the effects on differentiation. This resulted in an approximately threefold increase in neurogenesis, a threefold decrease in astrogliogenesis and a 50% decrease in oligodendrogenesis. In conclusion, this study suggests that reduced signalling through MORs and DORs decreases proliferation in rat AHPs, increases the number of in vitro-generated neurons and reduces the number of astrocytes and oligodendrocytes in culture.
Asunto(s)
Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Antagonistas de Narcóticos/farmacología , Neuronas/efectos de los fármacos , Receptores Opioides delta/antagonistas & inhibidores , Receptores Opioides mu/antagonistas & inhibidores , Células Madre/efectos de los fármacos , Células Madre/metabolismo , betaendorfina/metabolismo , Animales , Apoptosis , Astrocitos/efectos de los fármacos , Western Blotting , Recuento de Células , Técnicas de Cultivo de Célula , Diferenciación Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Inmunohistoquímica , L-Lactato Deshidrogenasa/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mitosis/efectos de los fármacos , Neuronas/metabolismo , Oligodendroglía/efectos de los fármacos , Análisis de Secuencia por Matrices de Oligonucleótidos , Radioinmunoensayo , Ratas , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacosRESUMEN
A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity.