Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Acta Diabetol ; 54(7): 663-668, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28409274

RESUMO

AIMS: Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. METHODS: In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([3H]AZ1, [3H]AZ2 and [3H]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma. RESULTS: [3H]AZ1 showed improved specificity to FFAR1, with decreased off-target binding compared to [3H]AZ2 and [3H]TAK-875, while retaining high affinity in the nanomolar range. FFAR1 density in human islets was approximately 50% higher than in exocrine tissue. CONCLUSIONS: AZ1 is a suitable lead compound for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity and reduced off-target binding.


Assuntos
Células Secretoras de Insulina/metabolismo , Imagem Molecular/métodos , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/metabolismo , Animais , Benzofuranos/química , Benzofuranos/farmacocinética , Linhagem Celular Tumoral , Descoberta de Drogas/métodos , Células HEK293 , Humanos , Insulina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pâncreas/metabolismo , Ligação Proteica , Ratos , Sulfonas/química , Sulfonas/farmacocinética , Trítio/química , Trítio/farmacocinética
2.
Acta Diabetol ; 53(3): 413-21, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26467464

RESUMO

AIMS: To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2. METHODS: GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [(3)H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [(3)H]DTBZ. RESULTS: GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [(3)H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-ßH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [(3)H]AZD 3825 than for [(3)H]DTBZ. CONCLUSION: GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.


Assuntos
Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Células HEK293 , Humanos , Especificidade de Órgãos , Ratos , Receptores Imunológicos/genética , Receptores de Prostaglandina/genética , Proteínas Vesiculares de Transporte de Monoamina/genética , Proteínas Vesiculares de Transporte de Monoamina/metabolismo
3.
Amyloid ; 21(1): 21-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24286359

RESUMO

Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar proteins arranged in ß-pleated sheets. [(11)C]PIB has been used in PET studies to assess Aß deposition in brain of patients with Alzheimer's disease (AD). The possibility to visualize other types of amyloid deposits with [(11)C]PIB would be of potential clinical importance in early diagnosis and for following therapeutic effects. In the present study, we evaluated in vitro binding of [(3)H]PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain (AL), amyloid protein A (AA) and Aß amyloid. We found significantly higher binding of [(3)H]PIB in tissue from systemic amyloidoses than in control tissue, i.e. 4.7 times higher (p < 0.05). [(3)H]PIB showed the highest affinity to cortex of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and AL type of amyloidosis and large variations in affinity were observed even within tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which disrupts the ß-sheet structure, decreased the protein levels and, concomitantly, the binding of [(3)H]PIB in all four types of amyloidoses.


Assuntos
Compostos de Anilina/química , Placa Amiloide/química , Compostos Radiofarmacêuticos/química , Tiazóis/química , Trítio/química , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Precursor de Proteína beta-Amiloide/química , Estudos de Casos e Controles , Humanos , Cadeias Leves de Imunoglobulina/química , Pessoa de Meia-Idade , Pré-Albumina/química , Ligação Proteica , Cintilografia , Proteína Amiloide A Sérica/química , Extratos de Tecidos/química
4.
Neurochem Int ; 54(5-6): 347-57, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19162107

RESUMO

beta-Amyloid (Abeta) deposits are one of the major histopathological hallmarks of Alzheimer's disease (AD). The amyloid-imaging positron emission tomography (PET) tracer [(11)C]PIB (N-methyl[(11)C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole) is used in the assessment of Abeta deposits in the human brain. [(11)C]PIB-amyloid interaction and insoluble Abeta40 and Abeta42 peptide levels in the brain were quantified in postmortem tissue from nine AD patients and nine age-matched control subjects in the temporal, frontal and parietal cortices and the cerebellum. Autoradiographical studies showed significantly higher densities of specific [(11)C]PIB-amyloid binding in gray matter in the temporal and parietal cortex (62fmol/mg tissue) in AD patients as compared to control subjects, whereas the density was somewhat lower in the frontal cortex (56fmol/mg tissue). No specific binding could be detected in the AD cerebellum or in the tissues from the control subjects (< or =5fmol/mg tissue). Insoluble Abeta40 and total Abeta levels (i.e. sum of Abeta40 and Abeta42) were significantly higher in patients than in controls in all measured cortical regions as determined using ELISA, which was confirmed using immunohistochemistry. The present findings show a more regional selective distribution of [(11)C]PIB amyloid binding than previously reported. Moreover, it is suggested that some of the [(11)C]PIB binding and insoluble Abeta seen in control subjects may be amyloid in the blood vessels.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Benzotiazóis , Encéfalo/metabolismo , Fragmentos de Peptídeos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/análise , Compostos de Anilina , Autorradiografia , Ligação Competitiva/fisiologia , Biomarcadores/análise , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/metabolismo , Angiopatia Amiloide Cerebral/fisiopatologia , Artérias Cerebrais/metabolismo , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Ensaio Radioligante , Cintilografia , Tiazóis
5.
Metabolism ; 54(2): 247-54, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15690320

RESUMO

Epidemiological studies associate smoking with reduced insulin secretion. We hypothesized that nicotine could negatively affect pancreatic beta-cell function. Acute or 48-hour exposures to nicotine (10(-4) to 10(-6) mol/L) moderately inhibited insulin release at basal (3.3 mmol/L) and/or elevated (27 mmol/L) glucose in rat and human islets. Acute exposure to nicotine (10(-6) mol/L) inhibited tolbutamide (200 micromol/L)-induced insulin release by 41% (P < .05), but did not affect secretion induced by KCl (20 mmol/L) or 3-isobutyl-1-methylxanthine (1 mmol/L) (tested in rat islets). Specific binding of [3H]nicotine was demonstrated in rat islets and in a beta -cell line of rat origin, INS-1. Such binding was enhanced by 48 hours of coculture with nicotine (10(-7) mol/L). Expression of mRNA for the nicotinic receptor subunits alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, and beta 2 was detected in INS-1 cells by reverse transcriptase polymerase chain reaction. Acute exposure to cytisine (10(-6) mol/L), an agonist of alpha 4, beta 2 subunits, partially inhibited tolbutamide-induced insulin release. Specific binding of alpha bungarotoxin (10(-10) mol/L), an antagonist of the alpha 7 subunit, could be demonstrated in INS-1 cells, and culture with alpha bungarotoxin modestly increased insulin release in postculture incubations at basal and elevated glucose, P < .05. Our data indicate that functional nicotinic receptors are present in pancreatic islets and beta cells.


Assuntos
Ilhotas Pancreáticas/metabolismo , Receptores Nicotínicos/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Alcaloides/farmacologia , Animais , Azocinas/farmacologia , Bungarotoxinas/farmacologia , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Insulina/biossíntese , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Nicotina/metabolismo , Nicotina/farmacologia , Agonistas Nicotínicos/metabolismo , Agonistas Nicotínicos/farmacologia , Quinolizinas/farmacologia , RNA/biossíntese , RNA/genética , RNA/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/biossíntese , Receptores Nicotínicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sais de Tetrazólio , Tiazóis
6.
Eur J Neurosci ; 19(10): 2703-10, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15147304

RESUMO

Ten days treatment with nicotine reduced insoluble amyloid A beta 1-40 and Alpha beta 1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more than that observed in 14.5-month-old mice following nicotine treatment for 5.5 months. A reduction in A beta associated with cerebral vessels was observed in addition to that deposited as parenchymal plaques after 5.5 months treatment. The diminution in A beta peptides observed was not accompanied by changes in brain alpha, beta or gamma secretase-like activities, NGF or BDNF protein expression measured in brain homogenates. A significant increase in sAPP was observed after nicotine treatment of SH-SY5Yneuroblastoma cells that could be blocked by the nicotinic antagonist mecamylamine. Attenuation of elevated [(125)I]-alpha bungarotoxin binding (alpha 7) in APPsw mice was observed after 5.5 months nicotine treatment. Both these observations suggest that the reduction in insoluble A beta by nicotine might be in part mediated via the alpha 7 nicotinic receptor. Further studies are required to identify potential mechanisms of the nicotine's amyloid-reducing effect.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Vasos Sanguíneos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Artérias Cerebrais/efeitos dos fármacos , Nicotina/administração & dosagem , Fatores Etários , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/sangue , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases , Western Blotting/métodos , Encéfalo/metabolismo , Química Encefálica , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Bungarotoxinas/farmacocinética , Linhagem Celular Tumoral , Artérias Cerebrais/metabolismo , Esquema de Medicação , Embrião de Mamíferos , Endopeptidases/metabolismo , Transportador de Glucose Tipo 1 , Humanos , Imuno-Histoquímica/métodos , Isótopos de Iodo/farmacocinética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas de Transporte de Monossacarídeos/metabolismo , Fator de Crescimento Neural/metabolismo , Neuroblastoma , Nicotina/farmacologia , Fragmentos de Peptídeos/análise
7.
Brain Res Dev Brain Res ; 142(2): 151-60, 2003 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-12711366

RESUMO

Neuronal nicotinic acetylcholine receptors are thought to be involved in regulation of several processes during neurogenesis of the brain. In this study the expression of the alpha7 nicotinic acetylcholine receptor subtype was investigated in human fetal (9-11 weeks of gestation), middle-aged (28-51 years) and aged (68-94 years) medulla oblongata, pons, frontal cortex, and cerebellum. The specific binding of the alpha7 receptor antagonist [(125)I]alpha-bungarotoxin was significantly higher in fetal than in both middle-aged and aged medulla oblongata and aged pons. No significant decrease in [(125)I]alpha-bungarotoxin binding sites was observed from fetal to adult cortex and cerebellum. The alpha7 mRNA expression was significantly higher in all fetal brain regions investigated, except for aged cortex, than in corresponding middle-aged and aged tissue. The high expression of alpha7 nicotinic acetylcholine receptors in fetal compared to adult brain supports the view that these receptors play an important role during brain development.


Assuntos
Encéfalo/embriologia , Encéfalo/metabolismo , Diferenciação Celular/genética , Neurônios/metabolismo , Receptores Nicotínicos/genética , Células-Tronco/metabolismo , Regulação para Cima/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/metabolismo , Sítios de Ligação/genética , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/genética , Encéfalo/citologia , Bungarotoxinas , Ciclofilinas/genética , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Neurônios/citologia , Mudanças Depois da Morte , RNA Mensageiro/metabolismo , Ensaio Radioligante , Células-Tronco/citologia , Receptor Nicotínico de Acetilcolina alfa7
8.
Brain Res ; 956(2): 358-66, 2002 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-12445706

RESUMO

Reductions in the number of neuronal nicotinic acetylcholine receptors (nAChRs) have been shown to occur in connection with Parkinson's disease (PD), but it is still unclear which subtype of this receptor is affected. In the present study we examined various nAChR subtypes employing ligand binding, as well as levels of subunit protein and mRNA in the brains of PD patients and age-matched controls. Binding of [3H]epibatidine and levels of alpha3 mRNA in the caudate nucleus and temporal cortex, but not in the hippocampus were significantly decreased in the PD brain. The level of the alpha3 protein subunit was significantly reduced in all these brain regions but there was no change in the level of alpha4. The level of the beta2 protein subunit in the temporal cortex and hippocampus and the beta2 mRNA in the temporal cortex was lowered. Both the levels of the alpha7 subunit protein and [125I]alpha-bungarotoxin binding were significantly increased in the temporal cortex of PD patients whereas the alpha7 mRNA level was unchanged. These findings reveal selective losses of the alpha3- and beta2-containing nAChRs and an increase in the alpha7 nAChRs that might be related to the pathogenesis of PD.


Assuntos
Encéfalo/metabolismo , Doença de Parkinson/metabolismo , Receptores Nicotínicos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Autopsia , Western Blotting , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Bungarotoxinas/farmacologia , Colinérgicos/farmacologia , Humanos , Radioisótopos do Iodo , Agonistas Nicotínicos/farmacologia , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trítio , Receptor Nicotínico de Acetilcolina alfa7
9.
Respiration ; 69(4): 289-93, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12169737

RESUMO

Many epidemiological studies support a relationship between maternal smoking during pregnancy and adverse neurobehavioral effects later in life. Prenatal exposure to tobacco seems to increase the risks for cognitive deficits, attention deficit/hyperactivity disorder, conduct disorder, criminality in adulthood and a predisposition in the offspring to start smoking and alcohol abuse. Nicotine readily crosses the placenta and the fetuses of mothers who smoke are exposed to relatively higher nicotine concentrations than their mothers. In the fetal brain nicotine can activate nicotinic receptors which play an important role during development of the brain. A direct specific action on the developing human brain is plausible during the major part of the prenatal life, since the nicotinic receptors are already present in the brain during the first trimester.


Assuntos
Encéfalo/efeitos dos fármacos , Feto/efeitos dos fármacos , Nicotina/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Fumar/epidemiologia , Animais , Encéfalo/embriologia , Cognição/efeitos dos fármacos , Feminino , Humanos , Gravidez , Receptores Nicotínicos/efeitos dos fármacos , Fumar/fisiopatologia
10.
Neurosci Lett ; 328(3): 269-72, 2002 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-12147323

RESUMO

The binding sites of nicotinic acetylcholine receptor (nAChR) subtypes were measured in the parietal cortex and hippocampus of transgenic mice carrying mutant human APPswe and presenilin 1 (PS1) genes (APPswe/PS1 mice) between the ages of 3 weeks and 17 months. Soluble and insoluble beta-amyloid peptide (Abeta1-40 and Abeta1-42) levels were investigated in parallel. No significant differences in binding sites of [(3)H]cytisine (alpha4beta2 nAChRs) and [(125)I]alpha-bungarotoxin (alpha7 nAChRs) were observed in APPswe/PS1 mice and wild-type control mice at any age studied. At three weeks of age, soluble Abeta1-40 was detectable in the parietal cortex and hippocampus of APPswe/PS1 mice, whereas Abeta1-42 was detectable from 12 months of age. A pronounced increase in insoluble Abeta1-42 was observed between 3 weeks and 17 months compared with that of insoluble Abeta1-40 in both brain regions, indicating a shift that favors accumulation of Abeta1-42 in older APPswe/PS1 mice. The findings indicate that elevated Abeta levels in the brains of APPswe/PS1 mice do not alter the number of alpha4beta2 and alpha7 receptors, the two major brain nAChR subtypes.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/fisiologia , Encéfalo/metabolismo , Proteínas de Membrana/fisiologia , Fragmentos de Peptídeos/metabolismo , Receptores Nicotínicos/metabolismo , Envelhecimento/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Sítios de Ligação , Hipocampo/metabolismo , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos/genética , Mutação/fisiologia , Lobo Parietal/metabolismo , Presenilina-1 , Isoformas de Proteínas/metabolismo , Valores de Referência
11.
Mol Cell Neurosci ; 20(2): 354-65, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12093166

RESUMO

The nicotinic (nAChRs) and muscarinic (mAChRs) acetylcholine receptors and acetylcholinesterase (AChE) activity were studied in the brains of APP(SWE) transgenic mice (Tg+) and age-matched nontransgenic controls (Tg-) that were between 4 and 19 months of age. A significant increase in the binding of 125I-labeled alpha-bungarotoxin (alpha7 nAChRs) was observed in most brain regions analyzed in 4-month-old Tg+ mice, preceding learning and memory impairments and amyloid-beta (Abeta) pathology. The enhanced alpha7 receptor binding was still detectable at 17-19 months of age. Increase in [3H]cytisine binding (alpha4beta2 nAChRs) was measured at 17-19 months of age in Tg+ mice, at the same age when the animals showed heavy Abeta pathology. No significant changes in [3H]pirenzepine (M1 mAChRs) or [3H]AFDX 384 (M2 mAChRs) binding sites were found at any age studied. The upregulation of the nAChRs probably reflects compensatory mechanisms in response to Abeta burden in the brains of Tg+ mice.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/biossíntese , Precursor de Proteína beta-Amiloide/genética , Encéfalo/metabolismo , Neurônios/metabolismo , Receptores Nicotínicos/metabolismo , Regulação para Cima/genética , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Sítios de Ligação/genética , Encéfalo/patologia , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Feminino , Deficiências da Aprendizagem/genética , Deficiências da Aprendizagem/metabolismo , Deficiências da Aprendizagem/fisiopatologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/patologia , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/genética , Placa Amiloide/metabolismo , Placa Amiloide/patologia , RNA Mensageiro/metabolismo , Ensaio Radioligante , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/genética , Receptor Nicotínico de Acetilcolina alfa7
12.
J Neurochem ; 81(3): 655-8, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12065674

RESUMO

Alzheimer's disease neuropathology is characterised by beta-amyloid plaques and neurofibrillary tangles. Inhibition of beta-amyloid accumulation may be essential for effective therapy in Alzheimer's disease. In this study we have treated transgenic mice carrying the Swedish mutation of human amyloid precursor protein [Tg(Hu.APP695.K670N-M671L)2576], which develop brain beta-amyloid deposits, with nicotine in drinking fluid (200 microg/mL) from 9-14.5 months of age (5.5 months). A significant reduction in amyloid beta peptide 1-42 positive plaques by more than 80% (p < 0.03) was observed in the brains of nicotine treated compared to sucrose treated transgenic mice. In addition, there was a selective reduction in extractable amyloid beta peptides in nicotine treated mice; cortical insoluble 1-40 and 1-42 peptide levels were lower by 48 and 60%, respectively (p < 0.005), whilst there was no significant change in soluble 1-40 or 1-42 levels. The expression of glial fibrillary acidic protein was not affected by nicotine treatment. These results indicate that nicotine may effectively reduce amyloid beta peptide aggregation in brain and that nicotinic drug treatment may be a novel protective therapy in Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Nicotina/administração & dosagem , Placa Amiloide/efeitos dos fármacos , Administração Oral , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/biossíntese , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Química Encefálica , Contagem de Células , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Progressão da Doença , Esquema de Medicação , Feminino , Proteína Glial Fibrilar Ácida/biossíntese , Hipocampo/química , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Condutos Olfatórios/química , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/biossíntese , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Fatores Sexuais , Resultado do Tratamento
13.
J Neurochem ; 80(3): 457-65, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11905992

RESUMO

The alpha7 nicotinic acetylcholine receptor subtype is believed to be involved in the regulation of neuronal growth, differentiation and synapse formation during the development of the human brain. In this study the expression of the alpha7 nicotinic acetylcholine receptor was investigated in human fetal brain and spinal cord of 5-11 weeks gestational age. Both the specific binding of [125I]alpha-bungarotoxin to prenatal brain membranes and the expression of alpha7 mRNA were significantly higher in the pons, medulla oblongata, mesencephalon and spinal cord of 9-11 weeks gestational age compared with cerebellum, cortex and subcortical forebrain. A significant positive correlation between gestational age and the expression of alpha7 mRNA was observed in all brain regions except cortex. A positive correlation was also observed between the gestational age and the [125I]alpha-bungarotoxin binding in the pons, medulla oblongata, mesencephalon, and cerebellum. Consequently, a significant relationship between the alpha7 mRNA levels and the binding sites for [125I]alpha-bungarotoxin was found in the fetal brain. The increasing levels of the alpha7 nicotinic acetylcholine receptor during the first trimester support the important role of nAChRs for the development of the central nervous system.


Assuntos
Sistema Nervoso Central/química , Sistema Nervoso Central/embriologia , Receptores Nicotínicos/análise , Receptores Nicotínicos/genética , Actinas/genética , Bungarotoxinas/metabolismo , Bungarotoxinas/farmacologia , Ciclofilinas/genética , Feto/química , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Humanos , Radioisótopos do Iodo , RNA Mensageiro/análise , Ensaio Radioligante , Receptores Nicotínicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor Nicotínico de Acetilcolina alfa7
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...