RESUMO
PURPOSE: Theories provide a structural knowing about concept relationships, practice intricacies, and intuitions and thus shape the distinct body of the profession. Capturing ways of knowing and being is essential to any professions' practice, education and research. This process defines the phenomenon of the profession - its existence or experience. Theory evaluation is a systematic criterion-based assessment of a specific theory. This study presents a theory analysis of the Dental Hygiene Human Needs Conceptual Model (DH HNCM). METHODS: Using the Walker and Avant Theory Analysis, a seven-step process, the DH HNCM, was analysed and evaluated for its meaningfulness and contribution to dental hygiene. The steps include the following: (i) investigate the origins; (ii) examine relationships of the theory's concepts; (iii) assess the logic of the theory's structure; (iv) consider the usefulness to practice; (v) judge the generalizability; (vi) evaluate the parsimony; and (vii) appraise the testability of the theory. FINDINGS: Human needs theory in nursing and Maslow's Hierarchy of Need Theory prompted this theory's development. The DH HNCM depicts four concepts based on the paradigm concepts of the profession: client, health/oral health, environment and dental hygiene actions, and includes validated eleven human needs that evolved overtime to eight. It is logical, simplistic, allows scientific predictions and testing, and provides a unique lens for the dental hygiene practitioner. With this model, dental hygienists have entered practice, knowing they enable clients to meet their human needs. CONCLUSION: For the DH HNCM, theory analysis affirmed that the model is reasonable and insightful and adds to the dental hygiene professions' epistemology and ontology.
Assuntos
Assistência Odontológica , Higienistas Dentários , Necessidades e Demandas de Serviços de Saúde , Modelos Teóricos , Saúde Bucal , Profilaxia Dentária , Humanos , Relações Profissional-PacienteRESUMO
RATIONALE: Information is sparse on neurotransmitter deficiencies in frontotemporal dementia (FTD), in particular with reference to distinct histological subgroups and Alzheimer's disease (AD). OBJECTIVES: To evaluate in FTD with the major histologies, and compare with AD and controls, neurotransmission indices, as these may help in developing treatment. MATERIALS AND METHODS: Post-mortem grey matter from Brodmann Area 21, 9 and 7 of 51 brains was assayed for ten neurochemical parameters indexing neurotransmission. Repeated measures analyses of variance were carried out for each parameter comparing groups (FTD vs AD vs control) at each anatomical site. RESULTS: In FTD only the indices of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, serotonin (5-HT)(1A) and 5-HT(2A) receptors were significantly reduced from control values. Of the ten parameters only 5-HT(1A) receptors showed significant group x site interaction. This reflected disproportionate reduction in frontal and temporal compared to parietal cortex. In FTD three other receptors (muscarinic, M(1), N-methyl-D: -aspartate, NMDA, and kainate), choline acetyltransferase (ChAT) activity, 5-HT and 5-hydroxyindoleacetic acid content and 5-HT reuptake site values were not significantly reduced from control values. Only 5-HT, 5-HT reuptake site and ChAT values were significantly higher in FTD than AD. NMDA receptor and ChAT values were significantly reduced from control only in AD. CONCLUSIONS: Neurochemical results in FTD indicate degeneration and loss of pyramidal neurones in frontotemporal neocortex, yet 5-HT afferents and 5-HT concentration, which are inhibitory on pyramidal neurones, were relatively preserved. This could lead to an excess of extraneural 5-HT causing underactivity of surviving pyramidal neurones. Pharmacotherapy with a 5-HT(1A) receptor antagonist may be indicated.
Assuntos
Demência/metabolismo , Lobo Frontal/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Serotonina/metabolismo , Lobo Temporal/metabolismo , Idoso , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Colina O-Acetiltransferase/metabolismo , Demência/patologia , Feminino , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/metabolismo , Lobo Parietal/patologia , Mudanças Depois da Morte , Receptor Muscarínico M1/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Receptores de Ácido Caínico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Estudos Retrospectivos , Lobo Temporal/patologia , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismoRESUMO
The excitatory amino acids as neurotransmitters in the neocortex, hippocampus, striatum, thalamus, amygdala, nucleus basalis of Meynert and cerebellum from rats aged 4 months, 12 months and 24 months have been examined by measuring sodium-dependent high affinity uptake of D-[3H]-aspartate into preparations containing synaptosomes. Calcium-dependent K(+)-stimulated release of endogenous glutamate from the nucleus basalis was also measured. The hippocampus and cerebellum failed to show significant age-related changes in uptake of D-[3H]-aspartate. D-[3H]-aspartate uptake decreased significantly in the neocortex (29%), striatum (29%), nucleus basalis (26%), amygdala (19%) and thalamus (16%) in the middle-aged rats as compared to the young rats, but the changes were not progressive with age. The release of glutamate from the nucleus basalis was unaltered during the aging process.
Assuntos
Envelhecimento/fisiologia , Aminoácidos/fisiologia , Encéfalo/fisiologia , Transmissão Sináptica/fisiologia , Fatores Etários , Animais , Feminino , Ratos , Ratos Endogâmicos , Substância Inominada/fisiologiaRESUMO
The concentration of somatostatin-like immunoreactivity (SLI) in lumbar cerebrospinal fluid was measured in clinically suspected examples of either Alzheimer's disease (AD) or Pick's disease and controls. No significant correlation was found between the concentration of SLI and the age (22-73 years) of controls. Histological examination of brain material from the demented patients enabled the samples to be divided into AD and examples of clinically suspected AD or Pick's disease without specific histological change. The mean concentration of SLI was only slightly reduced in patients with AD in the presenium compared to control, and was unaltered from control in the examples of AD of senile age. The group of demented patients without specific histological change had a reduced concentration of SLI in lumbar CSF compared to control patients.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Peptídeos/líquido cefalorraquidiano , Fatores Etários , Idoso , Antipsicóticos/uso terapêutico , Demência/tratamento farmacológico , Humanos , Pessoa de Meia-IdadeRESUMO
Localization and other studies of glutamatergic receptors are hampered, in part, as pyramidal neurons in the neocortex cannot yet be selectively destroyed in laboratory animals. Demonstration of glutamatergic neuron dysfunction in Alzheimer's disease may allow verification of a technique suitable for the study of these cells in disorders without histopathological hallmarks. This includes Major Depressive Disorder in the elderly which has a poor prognosis.
Assuntos
Doença de Alzheimer/patologia , Córtex Cerebral/patologia , Transtorno Depressivo/patologia , Glicina/metabolismo , Fatores Etários , Aminoácidos/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , HumanosRESUMO
There is little information about major constituents of the brain in Alzheimer's disease. In the case of amino acids most of the previous data are contradictory. These have been interpreted in an anatomic and neurotransmitter as well as a metabolic context. To help clarify this, the contents of 14 amino acids and ethanolamine were determined in samples of neocortex from diagnostic craniotomies of 15 demented patients (10 with Alzheimer's disease) and other neurosurgical procedures (57 patients, 18 with intractable depression). A comprehensive survey of the effects of possible complicating factors on the concentrations of amino acids showed that artefacts were few; this was in contrast to a post mortem series of brains (16 with Alzheimer's disease and 16 controls; six regions assayed). We have used the ante mortem data to provide the basis for an accurate comparison of amino acid values between Alzheimer and control samples. In Alzheimer's disease, the mean contents of many amino acids were slightly higher (sum of the increases of those significantly affected was 15 nmol/mg protein) whereas glutamate content alone was significantly reduced (by 16 nmol/mg protein). This was not a feature of depression or a group of patients with other dementias. Glutamate content of Alzheimer samples was related to pyramidal neuron density in cortical layer III. These alterations were detected relatively early during the course of Alzheimer's disease and are considered to be due to loss of corticocortical glutamatergic association pathways.
Assuntos
Doença de Alzheimer/metabolismo , Aminoácidos/metabolismo , Encéfalo/metabolismo , Glutamatos/metabolismo , Degeneração Neural , Neurônios/metabolismo , Doença de Alzheimer/patologia , Ácido Glutâmico , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/fisiologia , Concentração Osmolar , Mudanças Depois da MorteRESUMO
Twenty antagonist substances with varying potencies for central and peripheral postsynaptic muscarinic receptors have been examined for effects on the central presynaptic muscarinic autoreceptor. This has been monitored by measuring the stimulating effects of the substances on acetylcholine synthesis by rat neocortical tissue prisms. Dose-response curves for selected agents showed that maximal stimulation of synthesis was to 136-140% of the value without an antagonist. At a concentration of 1 microM, 17 of the substances caused a significant increase in synthesis, whilst at 0.01 microM significant stimulation occurred with only atropine, dexetimide, N-methyl-piperdin-4-yl (R)-2-cyclohexyl-2-hydroxyl-2-phenylacetate, quinuclidinyl benzilate (QNB) and scopolamine. Linear regression analysis between synthesis values obtained with the substances and published data for the effects on either cholinoceptor-agonist induced contraction of guinea-pig ileum or the binding of [3H]-QNB to rat forebrain membranes gave correlation coefficients of r = 0.84 (P less than 0.01), and r = 0.75 (P less than 0.02) respectively. The results provide no indication of a pharmacological difference between the central presynaptic muscarinic autoreceptor and central and peripheral postsynaptic muscarinic receptors.
Assuntos
Receptores Muscarínicos/efeitos dos fármacos , Acetilcolina/biossíntese , Amitriptilina/farmacologia , Animais , Atropina/farmacologia , Encéfalo/metabolismo , Masculino , Oxotremorina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
1. We have investigated an aspect of the regulation of cortical pyramidal neurone activity. Microdialysis was used to assess whether topical application of drugs (in 10 microliter) to fill a burr hole over the frontal cortex, where part of the corticostriatal pathway originates, would change concentrations of the excitatory amino acids glutamate and aspartate in the striatum of the anaesthetized rat. 2. Topical application of N-methyl-D-aspartate (NMDA, 2 and 20 mM) dose-dependently increased glutamate and aspartate concentrations in the striatum. Coapplication of tetrodotoxin (10 microM) blocked the NMDA-evoked rise in these amino acids. A calcium-free medium, perfused through the probe also blocked the rise, indicating that it was due to an exocytotic mechanism in the striatum. 3. It was hypothesized that the rise observed was due to an increase in the activity of the corticostriatal pathway. As 5-hydroxytryptamine1A (5-HT1A) receptors are enriched on cell bodies of corticostriatal neurones, a selective 5-HT1A-antagonist (WAY 100135) was coapplied with the lower dose of NMDA. Compared to NMDA alone, coapplication of 50 microM WAY 100135 significantly increased glutamate release. This effect was sensitive to tetrodotoxin and calcium-dependent. Application of 50 microM WAY 100135 alone significantly enhanced glutamate release above baseline; this was also tested at 100 microM (not significant). 4. Compared to NMDA alone, coapplication of WAY 100135 (20 microM) significantly enhanced aspartate release; the mean value was also increased (not significantly) with 50 microM. This rise was calcium-dependent, but not tetrodotoxin-sensitive. WAY 100135 (100 microM) reduced NMDA-induced aspartate release. WAY 100135 (100 microM) reduced NMDA-induced aspartate release. Application of the drug alone had no effect on basal aspartate release.5. Coapplication of the 5-HT1A agonist, 8-OHDPAT (5 sanM) with NMDA did not affect the NMDA evoked increase in glutamate and aspartate.6. Topical application of high potassium (100 sanM) to the surface of the cortex did not result in a detectable rise in striatal glutamate or aspartate.7. Perfusion of WAY 100135 (tested at 50 microM) through the dialysis probe did not affect glutamate oraspartate concentrations.8. It was concluded that a selective 5-HT1A-antagonist can increase the activity of corticostriatal pyramidal neurones. As in Alzheimer's disease hypoactivity of pyramidal neurones almost certainly exists, a selective 5-HT1A-antagonist may be potentially useful in the treatment of the cognitive symptoms of this disease.
Assuntos
Ácido Aspártico/metabolismo , Córtex Cerebral/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , N-Metilaspartato/farmacologia , Piperazinas/farmacologia , Células Piramidais/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Animais , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Sinergismo Farmacológico , Masculino , Sondas Moleculares , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de SerotoninaRESUMO
1. The interactions of chlormethiazole with gamma-aminobutyric acid (GABA) synthesis and release, and with ligand binding to sites associated with the GABAA-receptor complex and the GABAB-receptor have been studied in the rat. The GABAA-receptor was studied using [3H]-muscimol, [3H]-flunitrazepam was used to label the benzodiazepine modulatory site, and [35S]-butyl-bicyclophosphorothionate ([35S]-TBPS) to label the chloride channel. 2. Chlormethiazole had no effect on GABA synthesis in the cortex, hippocampus and striatum or on GABA release from cortical slices in vitro. Chlormethiazole did not displace [3H]-baclofen binding to the GABAB-receptor. 3. Chlormethiazole (IC50 = 140 microM) and pentobarbitone (IC50 = 95 microM) both inhibited [35S]-TBPS binding by increasing the rate of [35S]-TBPS dissociation. In addition, chlormethiazole caused an apparent decrease in the affinity of [35S]-TBPS binding. 4. Chlormethiazole enhanced the binding of [3H]-muscimol but had no effect on [3H]-flunitrazepam binding. In contrast, the sedative barbiturate pentobarbitone enhanced both [3H]-muscimol and [3H]-flunitrazepam binding. 5. It is concluded that the sedative and anticonvulsant effects of chlormethiazole are probably mediated through an action at the GABAA-receptor. However, chlormethiazole does not interact with the GABAA-receptor complex in an identical manner to the sedative barbiturate pentobarbitone.
Assuntos
Encéfalo/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes , Clormetiazol/farmacologia , Receptores de GABA-A/metabolismo , Animais , Baclofeno/farmacologia , Encéfalo/efeitos dos fármacos , Compostos Bicíclicos com Pontes/farmacologia , Canais de Cloro CLC-2 , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Flunitrazepam/farmacologia , Técnicas In Vitro , Masculino , Muscimol/farmacologia , Picrotoxina/farmacologia , Ratos , Receptores de GABA-A/efeitos dos fármacos , Ácido gama-Aminobutírico/biossínteseRESUMO
In situ hybridization histochemistry has been used to study the amount of M1 muscarinic receptor mRNA in temporal cortex from subjects with Alzheimer's disease and other neurodegenerative disorders, where the duration of terminal coma was known. Total polyadenylated mRNA and glutamate decarboxylase activity were also measured. Both muscarinic receptor mRNA and enzyme activity showed a significant decline with increasing duration of terminal coma, but were not related to diagnosis. Polyadenylated mRNA signal did not show an association with coma. These data indicate the need to consider the nature of the terminal illness in post mortem studies of mRNA as well as for neurochemical research.
Assuntos
Doença de Alzheimer/metabolismo , Coma/metabolismo , Hibridização de Ácido Nucleico , Poli A/análise , Mudanças Depois da Morte , RNA Mensageiro/análise , Lobo Temporal/química , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Coma/etiologia , Coma/patologia , Reações Falso-Negativas , Regulação da Expressão Gênica , Glutamato Desidrogenase/análise , Glutamato Desidrogenase/biossíntese , Humanos , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/biossíntese , Transtornos Neurocognitivos/complicações , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/patologia , Sondas de Oligonucleotídeos , Receptores Muscarínicos/análise , Receptores Muscarínicos/biossíntese , Lobo Temporal/patologiaRESUMO
A substantial loss of cortical cholinergic nerve endings, along with a much more circumscribed cortical degeneration of pyramidal neurons, almost certainly causes glutamatergic hypoactivity in live Alzheimer's patients. These selective pathologies are discussed in terms of therapy. An additional effect of some proposed treatments is emerging as there is evidence that processing pathways for beta-amyloid precursor proteins in cortical pyramidal neurons, a target cell for acetylcholine, are affected by neuronal activity.
Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Neurotransmissores/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Doença de Alzheimer/patologia , Animais , Núcleo Caudado/metabolismo , Núcleo Caudado/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Neurônios/metabolismo , Neurônios/patologia , Tratos Piramidais/metabolismo , Tratos Piramidais/patologiaRESUMO
The concentrations of L-aspartate, L-glutamate, L-serine, glycine and gamma-aminobutyric acid (GABA) were determined in repeated samples of ventricular CSF from five patients with severe closed head injury. The values were compared with those obtained from five subjects undergoing surgical treatment for intractable depression. In the head-injured patients, the concentrations of aspartate, glutamate and glycine were 2- to 8-fold higher and the concentration of GABA 56- to 317-fold higher than control values; the concentration of serine was unaffected. Spearman correlation analysis indicated that the concentration of glutamate significantly increased after injury (Rs = 0.60, p < 0.0001, n = 42), reaching an average concentration of about 7 microM 3 days after the injury. This is probably sufficient to cause further excitotoxicity, which suggests the use of excitatory amino acid receptor antagonists as a treatment following severe head injury may require prolonged administration for maximum therapeutic benefit.
Assuntos
Aminoácidos/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Neurotransmissores/líquido cefalorraquidiano , Adolescente , Adulto , Ventrículos Cerebrais , Humanos , L-Lactato Desidrogenase/líquido cefalorraquidiano , Masculino , Concentração OsmolarRESUMO
A method for the destruction of a sub-population of neocortical pyramidal neurones is described. The technique uses unilateral striatal injections of volkensin, a toxic lectin from Adenia volkensii, which undergoes retrograde axonal transport from the site of injection to destroy subcortically projecting pyramidal cells within the neocortex. Striatal volkensin injections produce a significant reduction in the number of large pyramidal neurones of the infragranular layer. The selectivity of the lesion was demonstrated by the preservation of glutamic acid decarboxylase mRNA positive cells, considered to be cortical interneurones within ipsilateral cortex. The binding of the serotonin 1A receptor agonist [3H]-8-hydroxy-2-(n-dipropylamino)tetralin, visualised by autoradiography, was reduced in areas showing loss of large cells, indicating that these receptors may be present on subcortically projecting pyramidal cells. Ricin, another toxin lectin, but effective as a suicide transport agent in only the peripheral nervous system, produced local striatal damage but no cortical cell loss. The selective destruction by volkensin of neocortical pyramidal neurones with subcortical projection targets should aid the neurobiological investigation of such cells. Additionally, data obtained using this technique may provide insights into the interpretation of biochemical findings in neurodegenerative disease in which pyramidal cell loss is a significant feature.
Assuntos
Córtex Cerebral/citologia , Glicoproteínas , N-Glicosil Hidrolases , Neurônios/efeitos dos fármacos , Lectinas de Plantas , Proteínas de Plantas/toxicidade , Animais , Autorradiografia , Córtex Cerebral/efeitos dos fármacos , Corpo Estriado , Glutamato Descarboxilase/biossíntese , Injeções , Masculino , Vias Neurais/citologia , Vias Neurais/fisiologia , Hibridização de Ácido Nucleico , Sondas de Oligonucleotídeos , Proteínas de Plantas/farmacocinética , Tratos Piramidais/citologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Proteínas Inativadoras de Ribossomos Tipo 2 , Ricina/toxicidadeRESUMO
The binding of [3H]kainic acid to caudate nucleus membranes prepared from brains of examples of Alzheimer's dementia and controls has been determined. No changes were detected in either the affinity or the number of kainate binding sites in the Alzheimer samples compared to control, although there was a large decrease in choline acetyltransferase activity.
Assuntos
Doença de Alzheimer/metabolismo , Núcleo Caudado/metabolismo , Colina O-Acetiltransferase/metabolismo , Ácido Caínico/metabolismo , Pirrolidinas/metabolismo , Adulto , Idoso , Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Sítios de Ligação , Núcleo Caudado/análise , Núcleo Caudado/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/análiseRESUMO
The K+-evoked release of 13 amino acids has been determined from tissue prisms of neocortex from patients of various ages, and from rats. Prisms were prepared from various regions of human neocortex obtained at neurosurgery. Upon depolarization aspartate, glutamate and gamma-aminobutyrate (GABA) were shown to be preferentially released. The efflux of glutamate was calcium-dependent. Prisms prepared from human neocortex obtained shortly after death also exhibited preferential K+-induced release of putative amino acid transmitters. Absolute concentrations released into the media were similar to those found for neurosurgical samples. Comparison of the release data for rat and human samples revealed that the efflux of aspartate, glutamate and GABA occurred to a greater extent from rat brain preparations. The K+-evoked release of glutamate from human samples showed a significant linear increase from 12 to 68 years of age.
Assuntos
Aminoácidos/metabolismo , Córtex Cerebral/metabolismo , Transmissão Sináptica , Idoso , Animais , Cálcio/metabolismo , Humanos , Potássio/farmacologia , Ratos , Ratos Endogâmicos , Estimulação Química , Transmissão Sináptica/efeitos dos fármacosRESUMO
Tissue prisms prepared from neurosurgical samples of temporal neocortex of Alzheimer and control patients, upon depolarization preferentially released aspartate, glutamate and gamma-aminobutyrate (GABA). The Alzheimer and control samples did not significantly differ in the pattern of amino acid release, although acetylcholine synthesis by the Alzheimer tissue prisms was greatly reduced. There was no correlation between the efflux of any amino and acetylcholine synthesis. These observations suggest that in Alzheimer's disease there are no major changes in the extracellular concentrations of these putative amino acid transmitters.
Assuntos
Doença de Alzheimer/metabolismo , Aminoácidos/metabolismo , Demência/metabolismo , Lobo Temporal/metabolismo , Acetilcolina/biossíntese , Ácido Aspártico/metabolismo , Glutamatos/metabolismo , Ácido Glutâmico , Humanos , Potássio/farmacologia , Lobo Temporal/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
The action of D-Cycloserine (DCS) at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex has been studied with membranes from inferior parietal cortex of patients with Alzheimer's disease. The maximal response of the site, measured using [3H]MK-801 binding, was 64% of that observed with glycine. Stimulation of binding induced by DCS in the presence of fixed concentrations of glycine resulted in a family of dose-response curves, consistent with the antibiotic having the property of a partial agonist at this glycine site. It is proposed that because of circumscribed glutamatergic pyramidal cell pathology DCS will have benefit for Alzheimer's patients over and above all other types of cognitive impairment.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ciclosserina/farmacologia , Maleato de Dizocilpina/metabolismo , Ionóforos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Maleato de Dizocilpina/química , Feminino , Humanos , Ionóforos/química , Ensaio Radioligante , Receptores de N-Metil-D-Aspartato/química , EstereoisomerismoRESUMO
The binding of [3H]MK-801 to the N-methyl-D-aspartate receptor complex of well-washed cortical membranes from brains of examples of Alzheimer's disease and controls has been determined in incubations containing either glutamate or glycine plus glutamate. No changes were detected in the IC50 values for inhibition by zinc in the Alzheimer's samples compared to control although 'glycine-dependent' binding of the [3H]-ligand was significantly reduced in Alzheimer's disease.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Glicina/farmacologia , Receptores de Neurotransmissores/metabolismo , Zinco/farmacologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/efeitos dos fármacos , Dibenzocicloeptenos/metabolismo , Maleato de Dizocilpina , Feminino , Humanos , Masculino , Receptores de N-Metil-D-Aspartato , Receptores de Neurotransmissores/efeitos dos fármacosRESUMO
Seven markers of ascending (corticopetal) dopaminergic, noradrenergic and serotonergic neurones and choline acetyltransferase activity have been studied postmortem in frontal and temporal cortex from subjects with Alzheimer's disease and compared with a matched group of controls. Dopaminergic neurones (concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid) were not deficient but some markers of the other neurones were affected. Noradrenaline and serotonin concentrations were reduced whereas the concentrations of their metabolites were either unaltered (5-hydroxyindoleacetic acid) or increased (3-methoxy-4-hydroxyphenylglycol). All deficits were most pronounced in the temporal cortex. Severely demented subjects had evidence of generalized neuronal loss, whereas those with moderate dementia showed significant loss of only choline acetyltransferase activity. In Alzheimer subjects, a significant relationship (inverse) was found between 5-hydroxyindoleacetic acid concentration and the number of neurofibrillary tangles.
Assuntos
Doença de Alzheimer/metabolismo , Aminas Biogênicas/análise , Lobo Frontal/análise , Lobo Temporal/análise , Ácido 3,4-Di-Hidroxifenilacético/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Dopamina/análise , Feminino , Ácido Homovanílico/análise , Humanos , Ácido Hidroxi-Indolacético/análise , Masculino , Metoxi-Hidroxifenilglicol/análise , Pessoa de Meia-Idade , Norepinefrina/análise , Serotonina/análiseRESUMO
Experimental lesions and quantitative autoradiography were used to investigate the cellular localisation of receptors. Lesions were produced by intrastriatal injections of either volkensin or ricin, only the former is retrogradely transported. Volkensin treatment caused significant losses in Fr1/Fr2 of neocortex in the number of infragranular pyramidal neurones and binding to deep cortical layers of both [3H]pirenzepine (muscarinic cholinergic m1 receptors) and [3H]kainate (kainate sensitive glutamate receptors). In common with previous findings, which also showed sparing of interneurones, supragranular pyramidal neurones were not reduced in number and the binding to deep cortical layers of [3H]8-hydroxy-2-(n-dipropylamino)tetralin (serotonin 1A receptors) was reduced. Significant increases in [3H]prazosin binding to both total alpha adrenoceptors and the alpha 1b subtype were observed in superficial layers. Adrenoceptors were not decreased in any layer. The binding of [3H] GABA to GABAA receptors was not affected at all. Muscarinic receptors and pyramidal neurones were also reduced in deep cortical layers of Par1/Par2 in common with serotonin 1A (5-HT1A) receptors and total alpha receptors were significantly decreased in the middle layers. Overall m1 and kainate receptors were less affected than 5-HT1A receptors. The results are discussed in terms of the biology of cortical pyramidal neurones, drugs for Alzheimer's disease and novel ligands for improving human brain in vivo scanning techniques.