RESUMEN
PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.
Asunto(s)
Adaptación Psicológica/fisiología , Cognición , Terapia de Reemplazo de Hormonas , Síndrome de Klinefelter , Calidad de Vida , Testosterona/uso terapéutico , Adulto , Terapia de Reemplazo de Hormonas/métodos , Terapia de Reemplazo de Hormonas/psicología , Humanos , Italia/epidemiología , Síndrome de Klinefelter/epidemiología , Síndrome de Klinefelter/psicología , Síndrome de Klinefelter/terapia , Masculino , Salud Mental , Pruebas de Estado Mental y Demencia , Determinación de la Personalidad , Distrés Psicológico , Conducta SexualAsunto(s)
Bulimia/genética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo Genético , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Bulimia/tratamiento farmacológico , Genotipo , Humanos , Glicoproteínas de Membrana/efectos de los fármacos , Proteínas de Transporte de Membrana/efectos de los fármacos , Proteínas del Tejido Nervioso/efectos de los fármacos , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND: Ghrelin and leptin are endogenous peripheral proteins involved in the regulation of eating behaviour. In particular, ghrelin stimulates hunger and promotes food ingestion, whereas leptin increases satiety and reduces food consumption. Therefore, alterations in the physiology of these peptides may play a role in the pathogenesis of eating disorders such as bulimia nervosa. In the present study, we investigated ghrelin and leptin responses to food ingestion in patients with bulimia nervosa. METHOD: Nine symptomatic drug-free bulimic women and 12 age-matched healthy women ingested a meal of 1207 kcal (60% carbohydrates, 23% fat and 17% proteins) at 12.00 a.m. and underwent blood sample collection before and 45, 60, 90, 120 and 180 min after the meal. Plasma levels of ghrelin, leptin, insulin and glucose were measured. RESULTS: In healthy women, circulating ghrelin exhibited a drastic decrease after the food intake whereas, in bulimic patients, this response was significantly blunted. No difference between the two subjects groups was observed in post-prandial profiles of plasma leptin, insulin and glucose. CONCLUSIONS: The lack of a leptin response to food ingestion, in both bulimic and healthy women, is compatible with the role of this peptide as long-term rather than short-term modulator of eating behaviour. The blunted ghrelin response to food ingestion may support the occurrence in bulimic subjects of an impaired suppression of the drive to eat following a meal. This may have implications for binge-eating.
Asunto(s)
Bulimia/sangre , Ingestión de Alimentos/fisiología , Leptina/sangre , Hormonas Peptídicas/sangre , Adulto , Glucemia/metabolismo , Bulimia/diagnóstico , Bulimia/psicología , Impulso (Psicología) , Femenino , Ghrelina , Humanos , Hambre/fisiología , Insulina/sangre , Periodo Posprandial/fisiología , Valores de Referencia , Respuesta de Saciedad/fisiologíaRESUMEN
Leptin is thought to modulate feeding behaviour, body weight and energy metabolism by acting through specific cellular receptors. Derangements of leptin production have been repeatedly reported in patients with anorexia nervosa (AN) or bulimia nervosa (BN), but no information has been provided on the functional status of leptin receptors in these disorders. Therefore, we measured plasma levels of leptin and its soluble receptor (Ob-Re) in a total of 130 women, including 22 patients with AN, 45 patients with BN, 18 patients with the binge-eating disorder (BED), 12 non-binge eating obese women and 33 healthy women. Circulating leptin was drastically reduced in underweight anorexics and normal-weight bulimics, but increased in overweight BED patients and non-binge-eating obese women. Conversely, plasma levels of Ob-Re were significantly increased in patients with AN or BN, but decreased in BED and non-binge-eating obese women. Significant inverse correlations were detected between plasma levels of leptin and those of Ob-Re in all the subject groups, except in non-binge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Ob-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated.
Asunto(s)
Anorexia Nerviosa/sangre , Bulimia/sangre , Leptina/sangre , Receptores de Superficie Celular/sangre , Adulto , Índice de Masa Corporal , Peso Corporal , Estradiol/sangre , Femenino , Humanos , Hidrocortisona/sangre , Prolactina/sangre , Receptores de Leptina , Valores de ReferenciaRESUMEN
Peripheral amino acid changes have been reported in schizophrenia, but results are not consistent. We measured serum levels of different amino acids in 11 neuroleptic-resistant schizophrenic patients before and after clozapine treatment and in 11 age- and sex-matched healthy subjects. The schizophrenic patients exhibited significantly higher levels of serum aspartate, glutamate, isoleucine, histidine and tyrosine and significantly lower concentrations of serum asparagine, tryptophan and serine. In patients, the ratio between tryptophan and large neutral amino acids (LNAA) was significantly lower than in matched controls, whereas the tyrosine/LNAA ratio did not differ significantly. Moreover, 12 weeks of clozapine administration significantly reduced serum levels of glutamate but did not restore the values observed in normal controls, nor did it affect other amino acid concentrations. These data show changes in serum amino acids that may influence central serotonergic, dopaminergic and glutamatergic transmission in neuroleptic-resistant schizophrenics.
Asunto(s)
Aminoácidos/sangre , Clozapina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Aminoácidos Neutros/sangre , Clozapina/efectos adversos , Femenino , Estudios de Seguimiento , Ácido Glutámico/sangre , Humanos , Masculino , Valores de Referencia , Esquizofrenia/sangreAsunto(s)
Clozapina/metabolismo , Fluvoxamina/farmacocinética , Esquizofrenia/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Antagonistas de la Serotonina/metabolismo , Adulto , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Leptin is known to regulate body weight, energy balance, and reproduction. Therefore, investigation of its physiology is of obvious interest in bulimia nervosa (BN), an eating disorder characterized by body weight-related psychopathology, acute changes in the energy balance, and reproductive alterations. To date, the few studies that have assessed leptin production in BN have had several limitations, including the measurement of blood leptin levels in treated patients and the lack of normal weight healthy controls, so that the information they provide is not conclusive. As the investigation of leptin dynamics is likely to be more informative, we decided to assess leptin response to acute fasting and refeeding in both untreated patients with BN and healthy controls. Twelve women meeting the diagnostic criteria for BN of the Diagnostic and Statistical Manual of Mental Disorders, and 10 healthy women of the same age range participated in a 3-day study. At 1800 h on day 1, they received a meal of 1088 Cal, with 53% carbohydrates, 17% protein, and 30% fat. Then, they fasted until 1800 h on day 2, when they received the same meal. On day 3, they received a standard hospital diet of 2600 Cal, divided into 3 meals, with the same percentages of nutrients as described above. Blood samples were collected at different time points for plasma leptin, glucose, and insulin measurements. In bulimic patients, plasma leptin values were significantly lower than in healthy women (P < 0.0001) and were positively related to body weight, expressed as body mass index (r = 0.86; P < 0.0001). The leptin response to the fasting/refeeding paradigm significantly differed between patients and controls (time x group interaction, P < 0.0001). In fact, in healthy subjects, acute fasting induced a 58% decline in the plasma leptin concentration, whereas such a decrease was only 7% in bulimic women (P < 0.001). After acute refeeding, plasma leptin increased in both groups, although in the patients it did not reach the absolute values observed in normal controls. No significant difference was observed between bulimics and controls in plasma insulin response to the fasting/refeeding paradigm, whereas an abnormal increase in blood glucose levels was observed in the patients after the first meal following acute fasting. We conclude that in untreated women with BN, leptin, despite its very low plasma values, still holds its function as a sensor of body weight changes, but loses its role of signaling acute changes in energy balance.
Asunto(s)
Bulimia/sangre , Ayuno/sangre , Leptina/sangre , Adulto , Glucemia/metabolismo , Bulimia/terapia , Ingestión de Alimentos/fisiología , Estradiol/sangre , Femenino , Humanos , Insulina/sangre , Prolactina/sangre , Factores de TiempoRESUMEN
Immune changes may occur in patients with anorexia nervosa (AN) or bulimia nervosa (BN), and a role for proinflammatory cytokines has been proposed in the pathogenesis of both disorders. We measured plasma levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble forms of the cytokine receptor proteins gp130 and leukemia inhibitory factor receptor (LIF-R), the anti-inflammatory Clara cell 16-kD protein (CC16), prolactin (PRL), cortisol and 17beta-estradiol in 21 anorexic women, 21 bulimic women and 21 healthy females. As compared to healthy subjects, anorexics exhibited significantly increased plasma levels of gp130 and LIF-R, whereas bulimics had significantly decreased blood concentrations of CC16. No significant differences emerged in the blood levels of the remaining immune parameters. Both patient groups manifested higher plasma levels of cortisol and reduced plasma concentrations of PRL and 17beta-estradiol. In anorexics, a significant negative correlation was found between plasma levels of gp130 or LIF-R and the body mass index. These findings do not support the hypothesis that proinflammatory cytokines may play a pathogenetic role in eating disorders.
Asunto(s)
Anorexia Nerviosa/inmunología , Bulimia/inmunología , Inhibidores de Crecimiento , Linfocinas , Uteroglobina , Adulto , Anorexia Nerviosa/sangre , Bulimia/sangre , Estradiol/sangre , Femenino , Humanos , Hidrocortisona/sangre , Inflamación/sangre , Inflamación/inmunología , Interleucina-1/sangre , Interleucina-6/sangre , Factor Inhibidor de Leucemia , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia , Proteínas de Membrana de los Lisosomas , Masculino , Glicoproteínas de Membrana/metabolismo , Prolactina/sangre , Proteínas/metabolismo , Receptores de Citocinas/metabolismo , Receptores OSM-LIF , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites was studied in 10 schizophrenic patients with residual negative symptoms. Patients stabilized on clozapine therapy (200-450 mg/day) received additional fluoxetine (20 mg/day) for eight consecutive weeks. During fluoxetine administration, mean plasma concentrations of clozapine, norclozapine and clozapine N-oxide increased significantly by 58%, 36% and 38%, respectively. There was no difference in negative symptomatology, as measured by the Scale for Assessment of Negative Symptoms, and the drug combination was generally well tolerated. The concomitant elevation in plasma levels of clozapine and its major metabolites suggests that fluoxetine inhibits the metabolism of clozapine by affecting pathways other than N-demethylation and N-oxidation. Close monitoring of clinical response and, possibly, plasma clozapine levels is recommended whenever fluoxetine is given to patients stabilized on clozapine therapy.
Asunto(s)
Antidepresivos de Segunda Generación/administración & dosificación , Antipsicóticos/farmacocinética , Clozapina/farmacocinética , Depresión/enzimología , Fluoxetina/administración & dosificación , Esquizofrenia/enzimología , Adulto , Antidepresivos de Segunda Generación/efectos adversos , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Biotransformación , Enfermedad Crónica , Clozapina/administración & dosificación , Clozapina/efectos adversos , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Inhibidores del Citocromo P-450 CYP2D6 , Depresión/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Monitoreo de Drogas , Quimioterapia Combinada , Femenino , Fluoxetina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/tratamiento farmacológicoRESUMEN
To investigate immune system function in obsessive-compulsive disorder (OCD) we measured plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) in 14 drug-free obsessive-compulsive patients and 14 matched healthy controls. No significant differences were observed between patients and controls in plasma levels of IL-1 beta and IL-6, whereas plasma levels of TNF-alpha were significantly lower (p = 0.001) in the former. Blood levels of prolactin did not differ between the two groups, whereas plasma cortisol concentrations were significantly higher in patients than in healthy subjects (p = 0.02). No significant correlation was found between immune parameters, on the one hand, and endocrine or psychopathological measures on the other. These results suggest that OCD is associated with a decreased production in TNF-alpha, but normal synthesis of IL-1 beta and IL-6.
Asunto(s)
Trastorno Obsesivo Compulsivo/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Análisis de Varianza , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Hidrocortisona/sangre , Interleucina-1/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana EdadRESUMEN
Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) were assessed in 17 chronic schizophrenic patients who had been drug-free for 3 weeks and in 17 age- and sex-matched healthy subjects. Plasma concentrations of both cytokines were measured again in 12 patients after a 10-week treatment with clozapine. Compared with healthy controls, drug-free schizophrenic patients exhibited similar plasma IL-6 concentrations, but significantly higher levels of TNF alpha. After clozapine treatment, blood concentrations of TNF alpha fell to normal levels. These preliminary data support an immune activation in drug-free schizophrenic patients and an effect of clozapine on immune parameters.
Asunto(s)
Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Interleucina-6/sangre , Esquizofrenia/sangre , Factor de Necrosis Tumoral alfa/análisis , Adulto , Femenino , Humanos , Masculino , Esquizofrenia/tratamiento farmacológicoRESUMEN
Plasma levels of clozapine and its major metabolites, N-desmethylclozapine and clozapine-N-oxide, were measured in 18 schizophrenic patients at different times (4, 6 and 24 weeks) during the course of treatment with multiple doses of the drug, by using high performance liquid chromatography (HPLC) with UV detection. Plasma levels of clozapine and N-desmethylclozapine were significantly higher in females than in males after 4 and 6 weeks, but not after 24 weeks, of treatment. No sex difference was found at any time with respect to plasma levels of clozapine-N-oxide.
Asunto(s)
Antipsicóticos/uso terapéutico , Clozapina/análogos & derivados , Clozapina/sangre , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Enfermedad Crónica , Clozapina/uso terapéutico , Femenino , Humanos , Masculino , Esquizofrenia/sangre , Factores Sexuales , Factores de TiempoRESUMEN
RNase protection assay and in situ hybridization were used to analyze the temporal and cellular changes in nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) mRNA content evoked by the lipophilic beta-adrenergic receptor agonist clenbuterol in adult rat brain. Clenbuterol elicited a threefold increase in NGF mRNA expression which was limited to the cerebral cortex. This increase was maximal at 5 h, still evident by 10 h, and declined to control levels by 24 h. By 10 h NGF protein was also increased. Elevated NGF mRNA hybridization following clenbuterol was localized in the superficial cortical layers II and III in large Nissl-pale cells, suggesting that NGF mRNA induction occurs in neurons. In the same animals, clenbuterol induced a twofold increase in the levels of bFGF mRNA in cerebral cortex and hippocampus. This increase was localized primarily in glial cells as demonstrated by bFGF mRNA hybridization over all cortical regions and by labeling of the stratum lacunosum moleculare of the hippocampus. Our results suggest that enhanced noradrenergic tone regulates expression of these two trophic factors by different synaptic mechanisms and suggest that neurotransmitter(s) can coordinate trophic influences on different cell populations.
Asunto(s)
Corteza Cerebral/metabolismo , Clenbuterol/farmacología , Factor 2 de Crecimiento de Fibroblastos/genética , Factores de Crecimiento Nervioso/genética , ARN Mensajero/metabolismo , Animales , Hipocampo/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Steady-state plasma levels of mianserin, amitriptyline, and nortriptyline were determined by HPLC in two groups of elderly depressed patients who underwent a 5-week treatment with mianserin (60 mg/day in three oral doses) or amitriptyline (75 mg/day in three oral doses). Both treatments proved to be effective in reducing depressive symptoms. In the mianserin group, responder patients had steady-state plasma concentrations of mianserin higher than nonresponders. No relationship was found between amitriptyline, nortriptyline, or amitriptyline+nortriptyline plasma levels and clinical response in amitriptyline treated patients.
Asunto(s)
Envejecimiento/psicología , Amitriptilina/sangre , Amitriptilina/uso terapéutico , Trastorno Depresivo/sangre , Trastorno Depresivo/tratamiento farmacológico , Mianserina/sangre , Mianserina/uso terapéutico , Anciano , Anciano de 80 o más Años , Amitriptilina/efectos adversos , Cromatografía Líquida de Alta Presión , Trastorno Depresivo/psicología , Humanos , Masculino , Mianserina/efectos adversos , Persona de Mediana Edad , Nortriptilina/sangre , Escalas de Valoración Psiquiátrica , Método Simple CiegoRESUMEN
At two weeks post-transplantation, sciatic nerves inserted into the lesioned septo-hippocampal pathway contain NGF levels more than twice that of normal nerves. These transplanted nerves also contain regenerating cholinergic axons. Moreover, transplanted animals exhibit septal NGF levels that are significantly greater than in animals with lesions only. These results suggest a role for NGF in the ingrowth of axons into the transplants and in the increase in ChAT(+) septal neurons previously observed at this post-transplant time.
Asunto(s)
Trasplante de Tejido Encefálico/fisiología , Hipocampo/fisiología , Factores de Crecimiento Nervioso/fisiología , Nervio Ciático/trasplante , Acetilcolinesterasa/metabolismo , Animales , Femenino , Hipocampo/metabolismo , Histocitoquímica , Técnicas para Inmunoenzimas , Degeneración Nerviosa/fisiología , Factores de Crecimiento Nervioso/metabolismo , Neuronas/fisiología , Sistema Nervioso Parasimpático/anatomía & histología , Sistema Nervioso Parasimpático/citología , Ratas , Ratas Endogámicas , Nervio Ciático/metabolismoRESUMEN
Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (Kd = 0.045 nM) and low (Kd = 21 nM) affinity 125I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50-90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that the levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.
Asunto(s)
Encéfalo/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Fisostigmina/farmacología , Receptores de Superficie Celular/metabolismo , Escopolamina/farmacología , Animales , Inhibidores de la Colinesterasa/farmacología , Factores de Crecimiento Nervioso/genética , Parasimpaticomiméticos/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas , Receptores de Factor de Crecimiento Nervioso , Factores de TiempoRESUMEN
The stimulation of beta-adrenergic receptors by isoproterenol increases nerve growth factor (NGF) biosynthesis in C6 rat glioma cells, suggesting that norepinephrine may regulate NGF biosynthesis in vivo. We have tested this hypothesis in 21-day-old rats by depleting catecholamine stores with reserpine. Northern blot analysis of NGF mRNA, in combination with a two-site enzyme immunoassay for NGF, showed that depletion of catecholamines was associated with a 3-fold increase in NGF mRNA, which was followed by a significant increase in the NGF content of cerebral cortex. The increase in NGF mRNA was most marked 9 hr after reserpine administration (2 mg/kg, subcutaneously) and was no longer apparent 24 hr after drug administration, when brain monoamine stores were still depleted. Moreover, the lowest dose of reserpine that significantly increased NGF mRNA levels induced only a small change in the content of cortical catecholamines. These results suggest that reserpine mediates the increase in NGF production by a mechanism other than monoamine depletion. Because reserpine increases plasma glucocorticoid concentrations through the pituitary-adrenal axis, we investigated whether adrenal steroids could be responsible for the induction of NGF biosynthesis. The effect of reserpine on NGF biosynthesis was abolished in adrenalectomized rats. Moreover, dexamethasone, a synthetic glucocorticoid, given at a dose of 0.5 mg/kg, subcutaneously, increased the amount of NGF mRNA and NGF in cerebral cortex. NGF biosynthesis in the central nervous system may, thus, be regulated by adrenocortical hormonal secretion.
Asunto(s)
Encéfalo/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Reserpina/farmacología , Corticoesteroides/sangre , Animales , Monoaminas Biogénicas/metabolismo , Northern Blotting , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Inyecciones Subcutáneas , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas , Reserpina/administración & dosificación , Esteroides/farmacología , Estimulación QuímicaRESUMEN
Northern blot hybridization analysis was used to study regulation of nerve growth factor receptor (NGFR) mRNA content by glucocorticoids. Treatment for 6 h with dexamethasone (1 microM) caused a 40% decrease of NGFR mRNA content in PC12 cells and a 60% decrease in C6-2B glioma cells which was time and dose dependent. Dexamethasone (1 microM/kg) administered s.c. for two days to 21-day-old rats, elicits a 60% decrease in NGFR mRNA content in septum. These results suggest that the expression of NGFR gene in the brain could be inhibited by endogenous glucocorticoids. Whether dexamethasone inhibits NGFR gene expression by directly affecting cis-regulatory elements in the promoter regions of the gene remains to be elucidated.
Asunto(s)
Encéfalo/metabolismo , Dexametasona/farmacología , Factores de Crecimiento Nervioso/metabolismo , ARN Mensajero/genética , Receptores de Superficie Celular/genética , Neoplasias de las Glándulas Suprarrenales , Animales , Encéfalo/efectos de los fármacos , Línea Celular , Relación Dosis-Respuesta a Droga , Glioma , Cinética , Feocromocitoma , ARN Mensajero/efectos de los fármacos , Ratas , Receptores de Factor de Crecimiento NerviosoRESUMEN
Bilateral (3 nmol/side) i.c.v. infusion of ethylcholine aziridinium ion (AF64A) causes a 70% decrease of hippocampal acetylcholine content lasting for longer than 30 days without changing the density of hippocampal recognition sites for muscarinic ligands. In hippocampal slices prepared from rats receiving i.c.v. AF64A, the activation of phosphoinositide turnover or the inhibition of cyclic AMP accumulation elicited by muscarinic receptor agonists is facilitated. This AF64A treatment also causes a long-lasting decrease of hippocampal norepinephrine and serotonin (5-HT) content. Even a smaller dose of AF64A (1.5 nmol/side) reduces the hippocampal 5-HT content. The number of alpha-1 adrenoceptor recognition sites is slightly increased by 3 nmol/side of AF64A and the stimulation of phosphoinositide turnover by norepinephrine is facilitated. In contrast the decrease of hippocampal 5-HT concentration elicited by AF64A fails to change the 5-HT receptor indices that were measured. These results indicate that in rat hippocampus muscarinic receptors and alpha-1 adrenoceptors are denervated by AF64A and that this denervation promotes a receptor supersensitivity. These results also suggest that we could not find appropriate conditions to express a complete specificity of AF64A in destroying cholinergic axons and therefore this drug cannot be used readily to induce a selective deficiency of central cholinergic transmission.