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BACKGROUND: Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD. OBJECTIVE: Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model. METHODS: To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase. RESULTS: Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats. CONCLUSION: Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.
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Cannabidiol/farmacología , Trastornos de Somnolencia Excesiva/tratamiento farmacológico , Hipotálamo/efectos de los fármacos , Sueño/efectos de los fármacos , Animales , Hipotálamo/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuronas/efectos de los fármacos , Neuropéptidos/metabolismo , Ratas , Trastornos del Sueño-Vigilia/tratamiento farmacológico , VigiliaRESUMEN
Transplantation of dopaminergic (DA) cells into the striatum can rescue from dopamine deficiency in a Parkinson's disease condition, but this is not a suitable procedure for regaining the full control of motor activity. The minimal condition toward recovering the nigrostriatal pathway is the proper innervation of transplanted DA neurons or their precursors from the substancia nigra pars compacta (SNpc) to their target areas. However, functional integration of transplanted cells would require first that the host SNpc is suitable for their survival and/or differentiation. We recently reported that the intact adult SNpc holds a strong neurogenic environment, but primed embryonic stem cells (ie, embryoid body cells, EBCs) could not derive into DA neurons. In this study, we transplanted into the intact or lesioned SNpc, EBCs derived from embryonic stem cells that were prompt to differentiate into DA neurons by the forced expression of Lmx1a in neural precursor cells (R1B5/NesE-Lmx1a). We observed that, 6 days posttransplantation (dpt), R1B5 or R1B5/NesE-Lmx1a EBCs gave rise to Nes+ and Dcx+ cells within the host SNpc, but a large number of Th+ cells derived only from EBCs exogenously expressing Lmx1a. In contrast, when transplantation was carried out into the 6-hydroxidopamine-lesioned SNpc, the emergence of Th+ cells from EBCs was independent of exogenous Lmx1a expression, although these cells were not found by 15 dpt. These results suggest that the adult SNpc is not only a permissive niche for initiation of DA differentiation of non-neuralized cells but also releases factors upon damage that promote the acquisition of DA characteristics by transplanted EBCs.
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Diferenciación Celular/fisiología , Dopamina/metabolismo , Células Madre Embrionarias/citología , Sustancia Negra/citología , Animales , Células Cultivadas , Cuerpo Estriado/citología , Cuerpo Estriado/metabolismo , Neuronas Dopaminérgicas/citología , Neuronas Dopaminérgicas/metabolismo , Proteína Doblecortina , Células Madre Embrionarias/metabolismo , Ratones , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Neurogénesis/fisiología , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Factores de Transcripción/metabolismoRESUMEN
The present study evaluates the possible antinociceptive effect of chromosphere transplants in rats injected with 6-hydroxydopamine (6-OHDA), a model of Parkinson's disease. Male adult Wistar rats received 40µg/0.5µl of 6-OHDA or 0.5µl of vehicle into the left substantia nigra (SNc). Rats were evaluated for mechanical allodynia, cold allodynia, thermal hyperalgesia and formalin. Rats with altered nociceptive threshold were transplanted with chromospheres. After transplant, rats were evaluated every week. Our results confirm that 6-OHDA injection into rat's SNc reduces mechanical, thermal, and chemical thresholds. Interestingly, chromospheres' transplant reverted 6-OHDA-induced allodynia and hyperalgesia. The antinociceptive effect induced by chromospheres was dopamine D2- and opioid-receptor dependent since sulpiride or naltrexone reverted its effect.
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Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Trastornos Parkinsonianos/fisiopatología , Animales , Células Cultivadas , Masculino , Microinyecciones , Naltrexona/farmacología , Oxidopamina/efectos adversos , Dimensión del Dolor , Trastornos Parkinsonianos/inducido químicamente , Ratas , Sustancia Negra/efectos de los fármacos , Sulpirida/farmacologíaRESUMEN
The objective of the present study was to assess the benefits of 1-week repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain (LBP). The visual analogue scale (VAS), Short Form McGill pain questionnaire (SF-MPQ), and Short Form 36 Health Survey were used to evaluate the effect of this treatment. Eighty-two patients diagnosed with LBP were divided randomly into three groups: rTMS-treated group, sham group, and physical therapy-treated group. We observed a significant reduction in VAS and SF-MPQ scores in the rTMS-treated group, but not in the sham group. Moreover, patients who received rTMS had a lower mean pain score than patients treated with physical therapy. Our study suggests that rTMS produces safe, significant, and long-term relief in patients with LBP without evident side effects. This study shows for the first time that long-term repeated sessions of rTMS decrease pain perception of LBP. Bioelectromagnetics. 37:527-535, 2016. © 2016 Wiley Periodicals, Inc.
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BACKGROUND AND AIMS: Olfactory testing is useful in the differential diagnosis of age-related pathologies. To provide baseline reference values for clinical use in Mexico City we investigated the relation between olfactory capabilities and the principal population parameters of age, sex, and smoking habits in a large sample of healthy inhabitants. METHODS: We applied the internationally recognized and commercially available Sniffin' Sticks test battery to 916 men and women from across the adult life span. The Sniffin' Sticks test evaluates three key aspects of olfactory function: 1) ability to detect an odor, 2) to discriminate between odors, and 3) to identify odors. RESULTS: We found a significant decline in olfactory function from the 5th decade of age, and that detection threshold was the most sensitive measure of this. We did not find a significant difference between men and women or between smokers and non-smokers. In confirmation of our previous studies of the negative effect of air pollution on olfactory function, Mexico City inhabitants had poorer overall performance than corresponding subjects previously tested in the neighboring but less polluted Mexican state of Tlaxcala. CONCLUSIONS: Although we basically confirm findings on general demographic patterns of olfactory performance from other countries, we also demonstrate the need to take into account local cultural, environmental and demographic factors in the clinical evaluation of olfactory performance of Mexico City inhabitants. The Sniffin' Sticks test battery, with some adjustment of stimuli to correspond to Mexican culture, provides an easily administered means of assessing olfactory health.
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Estado de Salud , Vías Olfatorias/fisiología , Olfato/fisiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento , Contaminación del Aire/efectos adversos , Femenino , Humanos , Masculino , México/etnología , Persona de Mediana Edad , Odorantes , Valores de Referencia , Factores Sexuales , Fumar/efectos adversos , Adulto JovenRESUMEN
Parkinson's disease is a neurodegenerative disease which often presents hyposmia (80-90% of the cases). We characterized the olfactory behavior in the model of 6-hydroxydopamine of Parkinson's disease. Mice were trained to discriminate between two odorants in a radial maze. One of the odorants was associated with water as a reward. 6-hydroxydopamine was injected directly into the dorsal striatum; after complete striatal denervation, olfactory performance was evaluated in a radial maze. In the first evaluation, experimental mice performed as control mice. After the first evaluation, the narine of the contralateral side to the striatal injection was closed and mice were evaluated again. The experimental group completely lost the capacity to discriminate between the odorant associated with the reward (heptaldehyde) and the unconditioned odorant (2-heptanone). We propose that the olfactory deficit was caused by dopaminergic denervation to the olfactory tubercle and nucleus accumbens.
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Cuerpo Estriado/fisiopatología , Discriminación en Psicología/fisiología , Aprendizaje por Laberinto/fisiología , Percepción Olfatoria/fisiología , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/psicología , Anfetamina/farmacología , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Lateralidad Funcional , Inmunohistoquímica , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Pruebas Neuropsicológicas , Oxidopamina , Trastornos Parkinsonianos/patología , RecompensaRESUMEN
THE QUESTION TO SOLVE IN THE PRESENT WORK IS: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.
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Manganese is of growing concern as a toxic air pollutant. It is readily transported from the olfactory epithelium to the olfactory bulb, and unlike other metals, it is transported transynaptically to structures deep within the brain. However, little is known regarding the possible effect of nonoccupational exposure to manganese on olfactory function. Using the Sniffin' Sticks test battery, we compared the olfactory performance of subjects from a manganese mining district living <1 km from a manganese processing plant, with nonexposed subjects living 50 km from the closest source of exposure (N = 30/group). Groups were matched for age, sex, and schooling, and none had ever worked in mining-related activities. Concentrations of manganese in hair were measured as a biomarker of exposure; exposed subjects had significantly higher concentrations than nonexposed subjects. They were also significantly outperformed by the nonexposed subjects on all olfactory measures (threshold, discrimination, and identification), indicating adverse effects of manganese exposure on a range of olfactory functions, including those involving higher order cognitive processes. This contrasts with previous findings showing adverse peripheral but not central effects on olfactory function of big city air pollution, which mostly consists of toxicants known to affect the olfactory epithelium but with lower transynaptic transport capacity compared with manganese. We conclude that nonoccupational exposure to airborne manganese is associated with decrements in both peripheral and central olfactory function.
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Contaminantes Atmosféricos/toxicidad , Exposición a Riesgos Ambientales , Cabello/química , Manganeso/toxicidad , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/fisiopatología , Olfato/efectos de los fármacos , Adulto , Contaminantes Atmosféricos/química , Femenino , Cabello/metabolismo , Humanos , Masculino , Manganeso/química , Persona de Mediana Edad , Odorantes , Umbral Sensorial/efectos de los fármacosRESUMEN
Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1µM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1-10µM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4ß2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-ß-erytroidine hydrobromide (DHßE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of 5-HT1A receptors of 5-HT DRN neurons.
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Corticosterona/sangre , Inhibición Neural/efectos de los fármacos , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Núcleos del Rafe/citología , Neuronas Serotoninérgicas/efectos de los fármacos , Aconitina/análogos & derivados , Aconitina/farmacología , Potenciales de Acción/efectos de los fármacos , Adrenalectomía , Animales , Dihidro-beta-Eritroidina/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Antagonistas Nicotínicos/farmacología , Piperazinas/farmacología , Piridinas/farmacología , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Serotonina/metabolismo , Serotonina/farmacología , Antagonistas de la Serotonina/farmacologíaRESUMEN
Orexins/hypocretins (OX) and melanin-concentrating hormone (MCH) neurons located in the lateral hypothalamus seem to modulate different stages of the sleep-wake cycle. OX are necessary for wakefulness and MCH appears to regulate rapid eye movement sleep (REMS). Likewise, endocannabinoids, the endogenous ligands for cannabinoid receptors 1 and 2 (CB1R, CB2R), also modulate REMS in rats. Moreover, it has been shown that the activation of the CB1R in the lateral hypothalamus of rats excites MCH neurons while inhibiting OX neurons in in vitro preparations. Hence, we assessed the effects of 2-arachidonoylglicerol (2-AG, an endocannabinoid) in the lateral hypothalamus on the sleep-wake cycle of rats. We also utilized the CB1R inverse agonist AM251 to further support the involvement of this receptor, and we performed double immunofluorescence experiments to detect c-Fos, as a marker of neural activation, in OX and in MCH neurons to determine which neurons were activated. Our results indicate that 2-AG increases REMS through CB1R activation, and increases c-Fos expression in MCH neurons. These results suggest that endocannabinoid activation of the CB1R in the lateral hypothalamus, which activates MCH neurons, is one mechanism by which REMS is triggered.
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Ácidos Araquidónicos/administración & dosificación , Endocannabinoides/administración & dosificación , Glicéridos/administración & dosificación , Hormonas Hipotalámicas/metabolismo , Hipotálamo/efectos de los fármacos , Melaninas/metabolismo , Neuronas/efectos de los fármacos , Hormonas Hipofisarias/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Sueño REM/efectos de los fármacos , Animales , Ácidos Araquidónicos/farmacología , Endocannabinoides/farmacología , Glicéridos/farmacología , Hipotálamo/citología , Hipotálamo/metabolismo , Masculino , Neuronas/metabolismo , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismoRESUMEN
Chromaffin cell transplants have been explored since the early 1980s as a promising alternative in different pathological states, mainly Parkinson's disease and chronic pain. Advances are significant since transplants have been performed in humans. The general mechanism of these transplants relies in the capacity of chromaffin cells to act as mini-pumps that release amines and peptides. Different strategies are being used to improve the efficacy of transplants. However, a remaining hurdle is to determine the viability across time and the interaction with the microenvironment of the graft. We analyzed previous and current results finding that although there is a lot of positive evidence, there is also a lack of molecular studies that support behavioral results. The present review gives an update on recent advances of chromaffin cell transplants and their future in the clinic.
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Células Cromafines/trasplante , Dolor Crónico/terapia , Enfermedad de Parkinson/terapia , Animales , Microambiente Celular , Células Cromafines/metabolismo , Dolor Crónico/fisiopatología , Modelos Animales de Enfermedad , Humanos , Enfermedad de Parkinson/fisiopatología , Factores de TiempoRESUMEN
In the present study, the effect of chromaffin cell transplant in the spinal cord was evaluated on formalin-induced mechanical secondary allodynia in the rat. Chromaffin cells were transplanted into the lumbar subarachnoid space before or after formalin injection. Subcutaneous formalin injection (50 µl, 1%) produced long-lasting secondary allodynia in the ipsilateral and contralateral hind paws. Once secondary allodynia was established, treatment with chromaffin cells produced a significant reduction in the nociceptive behavior in both hind paws. The antiallodynic effect was time-dependent since it was observed 15 days after chromaffin cell transplants but not before. On the other hand, pre-treatment with chromaffin cells prevented the expression of secondary allodynia in both hind paws in the rat. Antiallodynic effect of chromaffin cells was reverted with the non-selective opioid receptor antagonist naltrexone and the non-selective α(2)-adrenoceptor antagonist rauwolscine. Clusters of viable chromaffin cells labeled with anti-tyrosine hydroxylase antibodies were observed in the retrieved transplants 15 days after transplant. These results establish the analgesic efficacy of intrathecal chromaffin cells on formalin-induced secondary allodynia. Our data suggest that chromaffin cells release neuroactive substances including opioid peptides and adrenergic amines that reduce secondary allodynia in rats through activation of their receptors.
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Células Cromafines/trasplante , Formaldehído/efectos adversos , Hiperalgesia/metabolismo , Hiperalgesia/cirugía , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Opioides/metabolismo , Médula Espinal/patología , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Femenino , Hiperalgesia/inducido químicamente , Hiperalgesia/patología , Naltrexona/farmacología , Antagonistas de Narcóticos , Ratas , Ratas Wistar , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Yohimbina/farmacologíaRESUMEN
The loss of dopaminergic neurons in the substantia nigra compacta followed by striatal dopamine depletion is a hallmark of Parkinson's disease. After dopamine depletion, dopaminergic D(2) receptor (D(2)R)-class supersensitivity develops in striatal neurons. The supersensitivity results in an enhanced modulation of Ca(2+) currents by D(2)R-class receptors. However, the relative contribution of D(2)R, D(3)R, and D(4)R types to the supersensitivity, as well as the mechanisms involved, have not been elucidated. In this study, whole cell voltage-clamp recordings were performed to study Ca(2+) current modulation in acutely dissociated striatal neurons obtained from rodents with unilateral 6-hydroxydopamine lesions in the substantia nigra compacta. Selective antagonists for D(2)R, D(3)R, and D(4)R types were used to identify whether the modulation by one of these receptors experiences a selective change after dopaminergic denervation. It was found that D(3)R-mediated modulation was particularly enhanced. Increased modulation targeted Ca(V)2.1 (P/Q) Ca(2+) channels via the depletion of phosphatidylinositol 4,5-bisphosphate, an intracellular signaling cascade hard to detect in control neurons and hypothesized as being amplified by dopamine depletion. An imbalance in the striatal expression of D(3)R and its splice variant, D(3)nf, accompanied enhanced D(3)R activity. Because Ca(V)2.1 Ca(2+) channels mediate synaptic GABA release from the terminals of striatal neurons, reinforcement of their inhibition by D(3)R may explain in part the profound decrease in synaptic strength in the connections among striatal projection neurons observed in the dopamine-depleted striatum.
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Canales de Calcio Tipo N/fisiología , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Fosfoinositido Fosfolipasa C/deficiencia , Receptores de Dopamina D2/biosíntesis , Receptores de Dopamina D3/fisiología , Animales , Masculino , Ratones , Ratones Transgénicos , Ratas , Ratas Wistar , Transducción de Señal/fisiología , Simpatectomía/métodos , Regulación hacia Arriba/fisiologíaRESUMEN
Parkinson's disease is a movement disorder whose principal symptoms are tremor, rigidity, bradykinesia and postural instability. Initially, drugs like L: -dopa or dopaminergic agonists are able to control these symptoms, but with the progress of the disease these drugs become less effective. Previous studies have reported that repetitive transcranial magnetic stimulation (rTMS) can improve these motor symptoms. The objective of this study was to investigate the neural mechanisms through which 25 Hz rTMS may improve motor symptoms in Parkinson's disease. In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz. rTMS in 10 Parkinson's disease patients. Fifteen rTMS sessions were performed over the primary cortex on both hemispheres (one after the other) during a 12-week period. The patients were studied using functional magnetic resonance imaging during performance of a simple tapping and a complex tapping task, 1 week before the administration of the first rTMS session and just after the last session. rTMS improved bradykinesia, while functional magnetic resonance imaging showed different cortical patterns in prefrontal cortex when patients performed the complex tapping test. Furthermore, the improvement in bradykinesia is associated with caudate nucleus activity increases in simple tapping. Finally, we observed a relative change in functional connectivity between the prefrontal areas and the supplementary motor area after rTMS. These results show a potential beneficial effect of repetitive transcranial magnetic stimulation on bradykinesia in Parkinson's disease which is substantiated by neural changes observed in functional magnetic resonance imaging.
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Encéfalo/irrigación sanguínea , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/terapia , Estimulación Magnética Transcraneal/métodos , Estimulación Acústica/métodos , Anciano , Encéfalo/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Oxígeno/sangre , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
Sleep deprivation (SD) produces numerous deleterious changes in brain cells, including apoptosis. It has been demonstrated that growth hormone (GH) stimulates cell growth and counteracts apoptosis, although this anti-apoptotic effect has not been tested against SD. To determine the protective effect of GH administration on cell proliferation and survival in the dentate gyrus (DG) of the hippocampus after sleep deprivation; we injected Wistar adult rats with a low dose of recombinant human GH (rhGH 5 ng/kg) per seven days and then we gently sleep deprived the animals for 48 consecutive hours. 5-Bromodeoxiuridine (BrdU) was administered to assess cell proliferation after the GH treatment and NeuN was used as marker of cell fate. Our results indicate that GH produced a three fold increase in the number of BrdU positive cells within the DG [Control = 1044 ± 106.38 cells, rhGH = 2952 ± 99.84 cells, P<0.01]. In contrast, 48 h of SD significantly reduced cell proliferation but this effect was antagonized by the GH administration [SD = 540 ± 18.3 cells, rhGH + SD = 1116 ± 84.48 cells, P<0.004]. Paradoxically, SD and GH administration increased cell survival separately but no significantly compared with control animals. However, cell survival was increased in animals treated with rhGH+SD compared to rats injected with saline solution [P<0.04]. Within the survival cells, the percentage of neurons was higher in SD animals [95%] compared with saline group, while this percentage (NeuN positive cells) was increased in animals treated with rhGH+SD [120%] compared with rhGH [25%] alone. Our findings indicate that GH strongly promotes cell proliferation in the adult brain and also protects the hippocampal neuronal precursors against the deleterious effect of prolonged sleep loss.
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Proliferación Celular/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hormona de Crecimiento Humana/farmacología , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/patología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Privación de Sueño/patología , Animales , Hipocampo/patología , Hipocampo/fisiopatología , Hormona de Crecimiento Humana/fisiología , Humanos , Degeneración Nerviosa/prevención & control , Neuronas/patología , Ratas , Ratas Wistar , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/fisiología , Privación de Sueño/complicacionesRESUMEN
Cannabidiol (CBD) is a constituent of Cannabis sativa that induces nonpsychotropic effects, and some of its biological actions in sleep have been described by the authors' group. Here, the authors report that when administered 10 or 20 microg/1 microl during the lights-on period directly into either lateral hypothalamus (LH) or dorsal raphe nuclei (DRN), which are wake-inducing brain areas, CBD enhanced wakefulness and decreased slow wave sleep and REM sleep. Furthermore, CBD increased alpha and theta power spectra but diminished delta power spectra. Additionally, CBD increased c-Fos expression in LH or DRN. These findings suggest that this cannabinoid is a wake-inducing compound that presumably activates neurons in LH and DRN.
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Cannabidiol/farmacología , Cannabis/química , Vigilia/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electroencefalografía , Electromiografía , Área Hipotalámica Lateral/efectos de los fármacos , Área Hipotalámica Lateral/fisiología , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , Distribución Aleatoria , Núcleos del Rafe/efectos de los fármacos , Núcleos del Rafe/fisiología , Ratas , Ratas Wistar , Sueño/efectos de los fármacosRESUMEN
In this study, we compared the depression-like symptoms induced by olfactory bulbectomy (OBX) in the two inbred Wistar and Long Evans rat strains. We also analyzed the self-regulated oral intake of nicotine in these strains and the effect of nicotine on the depression-like symptoms of olfactory bulbectomy. Furthermore, we compared the antidepressant-like effects of nicotine on Wistar rats to those of transcranial magnetic stimulation (TMS), which has emerged as a therapeutic alternative for depression management. Our results show that Wistar rats develop depression-like symptoms, demonstrated by the forced swim test (FST), 4 weeks after OBX. However, in bulbectomized Long Evans rats these symptoms cannot be assessed due to a higher degree of variability of the swimming behavior of this strain. These results suggest that there are some innate differences in susceptibility to stress between these two rat strains. In Wistar rats, voluntary oral nicotine intake (1.2 mg/(kg day) for 14 days) as well as nicotine administered as a single daily i.p. injection (1.5 mg/(kg day) for 14 days) decrease the depression-like symptoms of OBX. Daily transcranial magnetic stimulation (60 Hz and 0.7 mT for 2h/day for 14 days) also decreases depression-like symptoms but is less effective than nicotine. In conclusion, our results support the idea that there are possible innate differences for depression susceptibility and that nicotine and TMS may be useful in the treatment of this syndrome.
Asunto(s)
Conducta Animal/efectos de los fármacos , Depresión/terapia , Nicotina/farmacología , Bulbo Olfatorio/cirugía , Estimulación Magnética Transcraneal/psicología , Animales , Antidepresivos/administración & dosificación , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Depresión/psicología , Modelos Animales de Enfermedad , Esquema de Medicación , Conducta Exploratoria/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Actividad Motora/efectos de los fármacos , Nicotina/administración & dosificación , Nicotina/uso terapéutico , Bulbo Olfatorio/fisiología , Psicología Comparada , Ratas , Ratas Long-Evans , Ratas Wistar , Autoadministración , Especificidad de la Especie , Natación/fisiología , Natación/psicología , Estimulación Magnética Transcraneal/métodosRESUMEN
We investigated whether administration of MOD in rats during the lights-on period into wake-promoting areas, such as anterior hypothalamus (AH) or into the pedunculopontine tegmental nucleus (PPTg) would enhance waking. Results showed that microinjections of 1 microL of MOD (10, 20, or 30 microg) into both brain areas increased the total time of alertness and decreased sleep. Additionally, MOD-treated rats showed an enhancement in alpha power spectra but delta power spectra was diminished. Finally, c-Fos expression was found increased into either AH or the PPTg. Collectively, these results suggest that MOD induces waking via the activity of two wake-related brain areas such as AH and the PPTg.
Asunto(s)
Núcleo Hipotalámico Anterior/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Núcleo Tegmental Pedunculopontino/efectos de los fármacos , Vigilia/efectos de los fármacos , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electroencefalografía/métodos , Masculino , Modafinilo , Proteínas Oncogénicas v-fos/metabolismo , Ratas , Ratas Wistar , Fases del Sueño/efectos de los fármacosRESUMEN
Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterized in these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prism adaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather, patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degree of adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly, SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect. Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia.
Asunto(s)
Adaptación Fisiológica/fisiología , Ataxias Espinocerebelosas/fisiopatología , Adolescente , Adulto , Anciano , Electronistagmografía , Femenino , Efecto Tardío Figurativo/fisiología , Humanos , Aprendizaje/fisiología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Movimientos Sacádicos/fisiología , Ataxias Espinocerebelosas/clasificaciónRESUMEN
Few studies have evaluated the impact of smoking cessation on objective measures of sleep. The present study assessed the long-term effects of tobacco smoking abstinence on sleep and depression. A total of 15 chronic smokers with Hamilton Rating Scale for Depression (HAM-D) scores of less than 9 were evaluated. Subjects were screened for baseline data when they were smoking chronically. They underwent a 5-week psychological treatment for tobacco smoking, after which their depressive symptoms and sleep architecture were evaluated at 1, 2, 4, 6, 9, and 12 months of abstinence. We report the results of the seven patients who completed 1 year of evaluations and of those patients who achieved only partial abstinence. Polysomnographic recordings were taken, level of depression was measured with the HAM-D, and urinary cotinine levels also were evaluated. HAM-D scores were analyzed with and without sleep items. Nicotine abstinence reduced latency to rapid eye movement (REM) sleep and increased HAM-D scores, suggesting that chronic smokers have depressive symptoms that may be controlled by nicotine administration.