RESUMEN
BACKGROUND: The decrease of maternal docosahexaenoic (DHA) status during pregnancy has been associated with postpartum depression, especially in women with a low intake of DHA. Since the DHA intake in the Netherlands is low, we investigated whether supplementation of low doses of DHA or DHA plus arachidonic acid (AA) during pregnancy and lactation could prevent depressive symptoms and sleep disturbances in this period. METHODS: Women were supplemented daily with placebo, DHA (220 mg) or DHA+AA (220 mg each) from week 16 of pregnancy till three months postpartum. Fatty acid analyses were performed in the available plasma samples at 16 and 36 weeks of pregnancy. Depressive symptoms were measured in weeks 16 and 36 of pregnancy and six weeks postpartum using EPDS and within one week postpartum using a blues questionnaire. RESULTS: 119 women completed the study. The average frequency of fish intake was low, 0.94 times per week, and did not differ between the groups. The supplementation groups did not differ in mean EPDS scores or changes in EPDS scores, nor in incidence or severity of postpartum blues. Red blood cell DHA, AA and DHA/AA ratio did not correlate with EPDS or blues scores. Indices of sleep quality did not differ between the groups. CONCLUSION: Supplementation of 220 mg/day DHA or DHA+AA (220 mg/day each) does not prevent peri-partum depressive symptoms, in a population based sample with low background DHA intake. TRIAL REGISTRATION: ISRCTN Register nr. ISRCTN58176213.
Asunto(s)
Ácido Araquidónico/administración & dosificación , Depresión Posparto/prevención & control , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Adulto , Ácido Araquidónico/sangre , Ácidos Docosahexaenoicos/sangre , Femenino , Humanos , Placebos , Embarazo , Sueño/efectos de los fármacosRESUMEN
The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease. Experimental data have shown that proline-rich polypeptides isolated from bovine neurohypophisis possess neuroprotective and neuromodulatory properties in mice with aluminum neurotoxicosis or neuronal damage caused by venoms and toxins. Proline-rich polypeptides from ovine colostrums, so called Colostrinin, have been shown to produce cognitive improvement in an experimental model and in patients with Alzheimer disease. However, the precise mechanism underlying the neuroprotective action of proline-rich polypeptides is not very well established. Moreover, studies pointing at a neuroprotective effect of proline-rich polypeptides from bovine neurohypophisis in humans have not been reported thus far. The authors conclude that more detailed information on the mode of action of proline-rich polypeptides is needed as well as confirmation of their efficacy in broad clinical trials before this approach can really show its potential in the treatment of neurodegenerative disorders.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Péptidos/uso terapéutico , Prolina/uso terapéutico , Animales , Caspasas/metabolismo , Ensayos Clínicos como Asunto , Cognición/efectos de los fármacos , Síndrome de Aplastamiento/tratamiento farmacológico , Humanos , Hipotálamo/metabolismo , Inmunidad/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Síndromes de Neurotoxicidad/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Péptidos/química , Péptidos/metabolismo , Hipófisis/metabolismo , Prolina/químicaRESUMEN
We assessed essential fatty acid (EFA) and B-vitamin status, together with their determinants, in 61 patients with schizophrenia and established whether those with poor status responded biochemically to the appropriate dietary supplements. As a group, the patients had high erythrocyte saturated fatty acids (FAs), monounsaturated FA and low polyunsaturated FA of the omega3 and omega6 series. Patients reporting not to take vitamin supplements had low vitamin B12 and high homocysteine. Homocysteine variance proved best explained by folate in both the total group and male patients, and by vitamins B12 and B6 in females. Alcohol consumption and duration of illness are risk factors for low polyunsaturated FA status (< P2.5 of reference range), while male gender and absence of fish consumption predict hyperhomocysteinemia (> P97.5 of reference range). Two patients exhibited biochemical EFA deficiency and seven showed biochemical signs of omega3/docosahexaenoic acid (DHA) marginality. Four patients exhibited moderate hyperhomocysteinemia with plasma values ranging from 57.5 to 74.8 micromol/L. None of the five patients with either moderate hyperhomocysteinemia, biochemical EFA deficiency, or both, was predicted by their clinicians to have poor diets. That diet was nevertheless at the basis of these abnormalities became confirmed after supplementing 4 of them with B vitamins and with soybean and fish oils. We conclude that a subgroup of patients with schizophrenia has biochemical EFA deficiency, omega3/DHA marginality, moderate hyperhomocysteinemia, or combinations. Correction seems indicated in view of the possible relation of poor EFA and B-vitamin status with some of their psychiatric symptoms, but notably to reduce their high risk of cardiovascular disease.
Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Esenciales/administración & dosificación , Esquizofrenia/dietoterapia , Vitamina B 12/sangre , Vitamina B 6/sangre , Complejo Vitamínico B/uso terapéutico , Deficiencia de Vitamina B/dietoterapia , Adolescente , Adulto , Estudios Transversales , Eritrocitos/química , Eritrocitos/metabolismo , Ácidos Grasos/análisis , Ácidos Grasos Esenciales/deficiencia , Ácidos Grasos Esenciales/metabolismo , Femenino , Aceites de Pescado/administración & dosificación , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Factores Sexuales , Aceite de Soja/administración & dosificación , Vitamina B 12/uso terapéutico , Vitamina B 6/uso terapéutico , Deficiencia de Vitamina B/sangre , Deficiencia de Vitamina B/diagnósticoRESUMEN
Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up-regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno-pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium-lesions was significantly increased compared with normal white matter. Uptake in T2-lesions was generally decreased, suggesting a PBR down-regulation. However, uptake values increased whenever a clinical or MR-relapse was present, suggestive for a dynamic process with a transient PBR up-regulation. During disease progression, an increase of normal-appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS.
Asunto(s)
Antineoplásicos , Isoquinolinas , Microglía/metabolismo , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/fisiopatología , Tomografía Computarizada de Emisión/métodos , Adulto , Factores de Edad , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Mapeo Encefálico , Estudios de Cohortes , Femenino , Humanos , Isoquinolinas/metabolismo , Isoquinolinas/uso terapéutico , Imagen por Resonancia Magnética/métodos , Masculino , Microglía/diagnóstico por imagen , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Lóbulo Parietal/metabolismo , Lóbulo Parietal/patología , Lóbulo Parietal/fisiopatología , Ensayo de Unión Radioligante/métodos , Recurrencia , Tálamo/diagnóstico por imagen , Tálamo/metabolismo , Tálamo/patologíaAsunto(s)
Atención , Corteza Cerebral/anomalías , Corteza Cerebral/crecimiento & desarrollo , Trastornos de la Sensación/etiología , Sensación/fisiología , Estimulación Acústica/métodos , Animales , Corteza Cerebral/efectos de los fármacos , Femenino , Habituación Psicofisiológica , Acetato de Metilazoximetanol/envenenamiento , Ruido , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Wistar , Reflejo de Sobresalto , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Trastornos de la Sensación/fisiopatologíaRESUMEN
We determined whether food restriction or the drugs nimodipine (Ca2+ antagonist) and deprenyl (a MAO-B inhibitor) prevent the development of stroke in the spontaneously hypertensive stroke-prone rat (SHR-SP). Forty male SHR-SP rats, in the age of 34 weeks, were exposed to various treatments. During a period of 27 weeks, survival and blood pressure were followed. In the control and deprenyl group, the blood pressure values remained unchanged; 50% had died after 27 weeks. All rats that were treated with nimodipine survived. After food restriction, 7/8 rats survived and showed a lower blood pressure. This study in SHR-PR rats shows the superiority of nimodipine on survival, and the potential of food restriction as a stroke-preventing measure.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Trastornos Cerebrovasculares/fisiopatología , Privación de Alimentos/fisiología , Longevidad/efectos de los fármacos , Inhibidores de la Monoaminooxidasa/farmacología , Nimodipina/farmacología , Selegilina/farmacología , Animales , Peso Corporal/efectos de los fármacos , Trastornos Cerebrovasculares/genética , Esperanza de Vida , Masculino , Ratas , Ratas Endogámicas SHR , Análisis de SupervivenciaRESUMEN
It has been suggested repeatedly that the non-heritable factors in the pathogenesis of schizophrenia involve abnormalities of prenatal neurodevelopment. Furthermore, post-mortem studies show neuropathology of apparently developmental origin in the entorhinal cortex and other brain regions of schizophrenic subjects. In an attempt to model a developmental defect of the entorhinal region in the rat, cerebrocortical proliferation was briefly interrupted during its earliest stages, when the entorhinal area is thought to undergo major cell division. Specifically, the experimental set-up involved the administration of methylazoxymethanol acetate (MAM) on 1 of 4 consecutive days of embryonal development, from E9 to E12. Analysis of the forebrain in adult animals shows reduction of the entorhinal cortex in rats treated on each of these days. This effect shifts from lateral to medial divisions of the entorhinal cortex with later administration of MAM, following a known developmental gradient. Morphological consequences of MAM administration appear to be largely confined to the entorhinal cortex in the groups treated on E9 to E11, although slight reductions of the frontal and occipital neocortex were also observed in these animals. MAM treatment on E12 produces relatively more widespread damage, as reflected among other in a small reduction of brain weight. The described brain abnormalities are not accompanied by obvious phenotypical changes in any, but the E12-treated group. They, moreover, involve cortical thinning, disorganised cortical layering, and abnormal temporal asymmetries. These finding bare some similarity to observations in brains of schizophrenic subjects. The possible relevance of this approach in modeling neurodevelopmental aspects of schizophrenia is discussed.
Asunto(s)
Corteza Entorrinal/efectos de los fármacos , Corteza Entorrinal/patología , Acetato de Metilazoximetanol/farmacología , Efectos Tardíos de la Exposición Prenatal , Esquizofrenia/patología , Animales , Modelos Animales de Enfermedad , Corteza Entorrinal/enzimología , Femenino , Lóbulo Frontal/enzimología , Lóbulo Frontal/patología , Edad Gestacional , Giro del Cíngulo/enzimología , Giro del Cíngulo/patología , Hipocampo/enzimología , Hipocampo/patología , Inmunohistoquímica , Isoenzimas/metabolismo , Masculino , Lóbulo Occipital/patología , Embarazo , Proteína Quinasa C/metabolismo , Ratas/embriología , Ratas WistarRESUMEN
BACKGROUND AND PURPOSE: L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model. METHODS: Rats were treated for 14 days with 2 mg/kg and 10 mg/kg L-deprenyl or saline. After surgery a 20-minute hypoxia/ischemia period was induced by simultaneous occlusion of the left common carotid artery and reduction of the percentage of oxygen in the gas mixture to 10%. Rats were killed 24 hours later. Silver staining was used to reveal damage in several brain regions. RESULTS: In the brain, both L-deprenyl dosages reduced damage up to 78% compared with the controls. Total brain damage was decreased from 23%-31% to 5%-9% with the L-deprenyl treatment (2 mg/kg: F1.13 = 6.956, P < .05; 10 mg/kg: F1.13 = 5.731, P < .05). In the striatum, significant treatment effects were found between both the L-deprenyl groups (2 mg/kg and 10 mg/kg, respectively) and the saline group (F1.13 = 14.870, P < .005; and F1.13 = 8.937, P = .01; respectively). In the thalamus, significant treatment effects were seen in the 2-mg/kg L-deprenyl group (F1.13 = 11.638, P < .005) and the 10-mg/kg group (F1.13 = 8.347, P < .05) compared with the control group. No significant damage decrease was seen in the hippocampus and the cortex. CONCLUSIONS: The results show that L-deprenyl is effective as a prophylactic treatment for brain tissue when it is administered before hypoxia/ischemia. Mechanisms responsible for the observed protection remain unclear. The regional differences in damage, however, are in accordance with the reported regional increase in superoxide dismutase and catalase activities after L-deprenyl treatment, suggesting the involvement of free radicals and scavenger enzymes.
Asunto(s)
Hipoxia Encefálica/prevención & control , Ataque Isquémico Transitorio/prevención & control , Inhibidores de la Monoaminooxidasa/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Selegilina/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Catalasa/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/patología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipoxia Encefálica/patología , Ataque Isquémico Transitorio/patología , Masculino , Inhibidores de la Monoaminooxidasa/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Prosencéfalo/efectos de los fármacos , Prosencéfalo/patología , Ratas , Ratas Wistar , Selegilina/administración & dosificación , Superóxido Dismutasa/metabolismo , Tálamo/efectos de los fármacos , Tálamo/patologíaRESUMEN
The possibility of using radiolabeled divalent cations to visualize nerve cell degeneration in the brain was investigated after intoxication with neurotoxins. At different survival times after the intracerebral injection of kainic acid or 6-hydroxydopamine, autoradiographs were made from brain sections of rats that had received 45CaCl2 intravenously 24 h before death. Brain sections, adjacent to those used for autoradiography, of the 6-hydroxydopamine-treated rats were used for histofluorescence of catecholamines to check the neurochemical effect of the treatment. These experiments show that radioactive Ca accumulates in brain tissue during a particular phase of degeneration. Not only could degenerating cell bodies be traced by 45Ca autoradiography, but also degenerating nerve terminals in the striato-nigral and nigro-striatal projection systems. In positron emission tomography (PET) studies, 55CoCl2 was used as a marker for Ca2+. Unilateral lesions of the cat forebrain, produced by kainic acid, could be imaged in vivo by PET with 55CoCl2. PET with this radiolabel may provide diagnostic potentials for human neurodegenerative disorders.
Asunto(s)
Autorradiografía , Encefalopatías/patología , Encéfalo/patología , Calcio/metabolismo , Degeneración Nerviosa , Neuronas/patología , Tomografía Computarizada de Emisión , Animales , Encéfalo/metabolismo , Encefalopatías/inducido químicamente , Cloruro de Calcio , Radioisótopos de Calcio , Gatos , Cobalto , Radioisótopos de Cobalto , Cuerpo Estriado/patología , Lóbulo Frontal/patología , Hipocampo/patología , Hidroxidopaminas , Ácido Kaínico , Masculino , Neuronas/metabolismo , Oxidopamina , Ratas , Ratas Endogámicas , Sustancia Negra/patologíaRESUMEN
Amino acid transmitters and cations were assessed in the frontal cortex and hippocampus of 12 Alzheimer's disease (AD), 4 multi-infarct dementia (MID) patients, and 12 age-matched controls. In the hippocampus, but not in the frontal cortex of AD patients we observed an increase of sodium (Na) and a decrease of potassium (K) and magnesium (Mg) content as compared to controls. Calcium (Ca) was not changed. These cation shifts were highly correlated with glutamate, which was significantly decreased in AD hippocampus. Hippocampal Na and K levels correlated also highly with gamma-aminobutyrate, cholineacetyltransferase and noradrenaline levels in the hippocampus and dementia scores. These results show that Na and K changes are sensitive markers for neurodegenerative processes in AD and suggest a loss of glutamatergic neurons in AD hippocampus.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Demencia/metabolismo , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Aminoácidos/metabolismo , Cationes/metabolismo , Demencia/patología , Femenino , Lóbulo Frontal/patología , Hipocampo/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The cations, calcium, magnesium, sodium, and potassium, putative amino acid transmitters, and total protein contents were assessed in the frontal cortex, putamen, and substantia nigra of Huntington's disease (HD) patients and age-matched nonneurologic control subjects. In the HD frontal cortex and HD substantia nigra, only small increases in sodium levels and decreases in potassium levels were observed, but in the HD putamen there were major cation shifts, suggesting a twofold increase of the extracellular space. In all three brain areas that were investigated, potassium was positively correlated with gamma-aminobutyric acid and in the putamen sodium was negatively correlated with the amino acid. These correlations suggest loss of gamma-aminobutyric acidergic neurons or nerve terminals in these areas. The elevation of sodium in the HD basal ganglia may be visualized in vivo by nuclear magnetic resonance of sodium.
Asunto(s)
Aminoácidos/metabolismo , Encéfalo/metabolismo , Cationes/metabolismo , Enfermedad de Huntington/metabolismo , Neurotransmisores/metabolismo , Adulto , Anciano , Femenino , Lóbulo Frontal/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Putamen/metabolismo , Sustancia Negra/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The influence of desmethylimipramine (DMI) on the release of endogenous gamma-aminobutyric acid (GABA) and some other amino acids from the rat thalamus was studied with a push-pull perfusion technique. Following HPLC the amino acids were fluorimetrically estimated. Added to the perfusion medium at a concentration of 10 mumol L-1, DMI caused a 5- to 10-fold increase in the release of GABA. Similar effects were found with imipramine, trimeprimine, haloperidol, and propranolol. The elevation of GABA release induced by DMI was Ca dependent. The release of aspartate and glutamate was also increased by DMI, but in contrast to K ions, DMI did not reduce the thalamic output of glutamine.
Asunto(s)
Aminoácidos/metabolismo , Desipramina/farmacología , Neurotransmisores/metabolismo , Tálamo/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Cloruro de Calcio/farmacología , Femenino , Glutamatos/metabolismo , Ácido Glutámico , Glutamina/metabolismo , Técnicas In Vitro , Cinética , Magnesio/farmacología , Cloruro de Magnesio , Masculino , Ratas , Ratas Endogámicas , Tálamo/efectos de los fármacosRESUMEN
Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg-1 to 15 mumol kg-1, 350 ng--5 mg kg-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or gamma-hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2 x 36 mumol kg-1 (10 mg kg-1), last dose 89 mumol kg-1 (25 mg kg-1), 2--3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.
Asunto(s)
Encéfalo/metabolismo , Imipramina/sangre , Animales , Tronco Encefálico/metabolismo , Cerebelo/metabolismo , Cuerpo Estriado/metabolismo , Relación Dosis-Respuesta a Droga , Lóbulo Frontal/metabolismo , Hidroxibutiratos/farmacología , Hipotálamo/metabolismo , Masculino , Mesencéfalo/metabolismo , Lóbulo Occipital/metabolismo , Ratas , Ratas Endogámicas , Oxibato de Sodio , Tiopental/farmacologíaRESUMEN
The distribution of the noradrenaline-containing neurons of the rat locus coeruleus has been investigated with retrograde labeling techniques using two different fluorescent tracers. Injections were placed in the prefrontal cortex, the striatum, the thalamus, the hippocampus, the cerebellar cortex and the lumbar spinal cord. No evidence for locus coeruleus projections to the striatum was found. Injections in the cortex, thalamus and hippocampus revealed not only ipsilateral but also contralateral labeling of cells in the locus coeruleus. Following unilateral or bilateral homo- or heterotopic injections of the two tracers several cells of the locus coeruleus were double labeled. Combined injections of the two fluorophores in any of these forebrain areas and in the spinal cord also produced double labeled cells. The majority of double labeled cells was located in an area between the ventral and the dorsal parts of the locus coeruleus. These results indicate that individual neurons of the locus coeruleus have the possibility to influence adrenergic receptors at remote areas in the central nervous system.
Asunto(s)
Axones/fisiología , Vías Eferentes/anatomía & histología , Locus Coeruleus/anatomía & histología , Neuronas/fisiología , Animales , Corteza Cerebelosa/anatomía & histología , Corteza Cerebral/anatomía & histología , Cuerpo Estriado/anatomía & histología , Hipocampo/anatomía & histología , Masculino , Microscopía Fluorescente , Norepinefrina/análisis , Ratas , Médula Espinal/anatomía & histología , Tálamo/anatomía & histologíaRESUMEN
Evans Blue (EB) and a mixture of 4'-6'-diamidino-2-phenylindol 2 HCl and primuline (DAPI-Pr), fluorescing at different wave-lengths were injected into the rat hippocampus, frontal cortex or lateral part of the thalamus. After unilateral injection either of the two substances was retrogradely transported not only to ipsilateral but also to contralateral locus coeruleus (LC) neurons. Moreover after simultaneous injections of EB and DAPI-Pr respectively into the opposite brain structures of individual animals double-labeled neurons were observed in the bilateral LC. Unilateral electrical stimulation of the LC induced significant decreases of norepinephrine and increases of 3-methoxy-4-hydroxyphenylethylene-glycol in both the ipsi- and contralateral frontal cortex and whole forebrain, respectively. These ipsi- and contralateral alterations of the amine and its metabolite correlated highly significantly. These results indicate that several LC neurons have both contralateral and bilateral projections to the brain areas mentioned above.