RESUMO
BACKGROUND: Societal preferences have to be taken into consideration to ensure difficult healthcare decisions are legitimate and acceptable. It has been interesting to ascertain whether attitudes towards the principles of public healthcare resources allocation are homogenous. In particular, it has been thought provoking to ask whether advancement in medical technologies, and growing accessibility issues due to scarcity of healthcare resources, have influenced the beliefs of the general public with regard to allocative principles in recent years. The objective of this study was to compare preferences towards the distribution of healthcare resources between younger and older members of society. METHODS: Discrete choice experiments using the equivalence of numbers technique and the social welfare function were conducted in Poland. Public preferences towards disease severity, and potential to benefit, as well as aversion to inequity, were elicited. In order to ensure full understanding of questions by the older respondents, a pilot study with ten respondents aged 65+ was conducted. RESULTS: In total, 52 adult respondents (seniors) and 45 students (juniors) were interviewed. While the first were unwilling to trade between different patients, the latter chose a higher number of individuals to compensate for the loss of ten patients with a more severe disease and a higher potential to treat everything else being equal. Juniors were more inequality averse compared to seniors as well. CONCLUSIONS: While the revealed preferences of seniors were egalitarian, juniors were more willing to differentiate between disease severity and potential to benefit. Differences in opinion between juniors and seniors should be considered in open dialogue regarding healthcare rationing. Insight into the preferences towards health maximization of the former group and the egalitarian beliefs of the latter group could be useful for decision makers in the search for public acceptance of allocation of scarce healthcare resources.
Assuntos
Atitude Frente a Saúde , Atenção à Saúde/organização & administração , Alocação de Recursos para a Atenção à Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/organização & administração , Opinião Pública , Adulto , Distribuição por Idade , Idoso , Comportamento de Escolha , Tomada de Decisões , Feminino , Prioridades em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polônia/epidemiologia , Valores Sociais , Inquéritos e QuestionáriosRESUMO
Lifestyle modifications, including dietary and physical activity, are treatments for many chronic health conditions. Therefore, there is continued interest in improving the quantity and quality of nutrition information provided to the patient by the physician. This paper reviews the evidence to support motivational interviewing and other similar strategies for nutrition communications. Limited but positive data were found.
Assuntos
Comunicação , Promoção da Saúde/métodos , Motivação , Ciências da Nutrição/educação , Relações Médico-Paciente , Humanos , Estilo de VidaRESUMO
The mechanism of action of lithium, the primary treatment for bipolar affective disorder, is unknown but may involve inhibition of second messenger production in the brain. Therefore, the concentrations of three second messengers, inositol 1,4,5 trisphosphate (Ins 1,4,5P3), cyclic adenosine monophosphate (AMP), and cyclic guanosine monophosphate (GMP), were measured in rat cerebral cortex and hippocampus after acute or chronic lithium administration, as well as after treatment with the cholinergic agonist pilocarpine alone or in combination with lithium at a dose that induces seizures only in lithium pretreated rats. Neither acute nor chronic lithium treatment altered the hippocampal or cortical concentration of Ins 1,4,5P3, cyclic AMP, or cyclic GMP. Pilocarpine administered alone increased Ins 1,4,5P3 in both regions, did not alter cyclic AMP, and slightly increased cyclic GMP in the cortex. Coadministration of lithium plus pilocarpine caused large increases in the concentrations of all three second messengers and the production of each of them was uniquely attenuated: lithium reduced pilocarpine-induced increases of Ins 1,4,5P3 in the cortex at 60 min; chronic lithium administration reduced stimulated cyclic AMP production in the hippocampus; and chronic lithium treatment impaired stimulated cyclic GMP production in both regions. In summary, chronic lithium treatment appeared only to reduce Ins 1,4,5P3 and cyclic AMP concentrations after a long period of stimulation whereas cyclic GMP production was reduced by chronic lithium administration after both short and long periods of stimulation. Thus cyclic GMP was most sensitive to lithium and lithium attenuation of second messenger formation may be most important in excessively activated pathways.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Cloretos/farmacologia , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Hipocampo/efeitos dos fármacos , Inositol 1,4,5-Trifosfato/metabolismo , Lítio/farmacologia , Convulsões/fisiopatologia , Animais , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Relação Dose-Resposta a Droga , Hipocampo/fisiopatologia , Cloreto de Lítio , Masculino , Pilocarpina/farmacologia , Ensaio Radioligante , Ratos , Ratos Endogâmicos , Convulsões/induzido quimicamenteRESUMO
In this article I describe challenges to medical-nutrition educators and an opportunity provided by the Association of American Medical Colleges Medical School Objectives Project. Brief snapshots of nutrition education are given during the family medicine residency and through continuing medical education programming. An argument is made to provide education that focuses not on knowledge, but on confidence and skill in providing nutrition services to primary care patients. Medical-nutrition educators are challenged to share curriculum ideas and to explore ways to use technology to become a more effective community.
Assuntos
Medicina de Família e Comunidade , Internato e Residência , Ciências da Nutrição/educação , Atenção Primária à Saúde , Currículo , Educação Médica Continuada , HumanosRESUMO
There is a need and a desire for educators working toward implementation of nutrition in medical schools and residency programs to share ideas and materials. The World Wide Web enables computer-mediated communications through which a medical nutrition curriculum could be discussed; however, existing formats lack focus and structure. In January 1999, a virtual seminar that focused on nutrition education in medical schools and residency programs was conducted. The seminar, titled "Making Room for Nutrition Education, was sponsored by organizations that have active medical nutrition educators. The seminar included 5 topics discussed over a 4-d period. The transcript was made available at http://www.preventivenutrition. com. There were 119 registered participants. Responses to a postseminar questionnaire were positive; there was interest in an ongoing series of virtual seminars.
Assuntos
Currículo , Educação Médica/métodos , Ciências da Nutrição/educação , Internet , Interface Usuário-ComputadorRESUMO
Norepinephrine and trans-1-aminocyclopentyl-1,3-dicarboxylic acid (ACPD) each individually stimulated hydrolysis of phosphoinositides and when tested in combination caused a stimulation that was 50-90% greater than additive in hippocampal and cortical slices of the rat but not in striatal slices. This synergistic augmentation of hydrolysis of phosphoinositide was evident with all stimulatory concentrations of norepinephrine and of ACPD up to 1 mM, at which point ACPD was inhibitory. A time-course study revealed no lag in the synergistic interaction and no down-regulation through 60 min of incubation of the augmented response to the combined agonists. The synergistic reaction was mediated by alpha 1-adrenergic receptors and by metabotropic excitatory amino acid receptors. Increased intracellular calcium, but not activation of protein kinase C, may play a role in mediating the synergistic interaction. Thus, a unique synergistic stimulatory interaction was found between two receptors coupled with phosphoinositide metabolism, a finding which also supports the suggestion that these two systems are co-localized in some cells.
Assuntos
Química Encefálica/efeitos dos fármacos , Cicloleucina/análogos & derivados , Norepinefrina/farmacologia , Fosfatidilinositóis/metabolismo , Animais , Biotransformação/efeitos dos fármacos , Cicloleucina/farmacologia , Sinergismo Farmacológico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hidrólise , Técnicas In Vitro , Inositol/metabolismo , Masculino , Propranolol/farmacologia , Ratos , Ratos Sprague-Dawley , Rutênio Vermelho/farmacologia , Verapamil/farmacologiaRESUMO
Following cholinergic denervation of the hippocampus by medial septal lesions, an unusual neuronal reorganization occurs in which peripheral adrenergic fibers arising from superior cervical ganglia grow into the hippocampus (hippocampal sympathetic ingrowth). Recent studies suggest that a similar process, in which sympathetic noradrenergic axons invade the hippocampus, can occur in Alzheimer's disease patients. In the last few years, the occurrence of apoptotic cell death has been studied in Alzheimer's disease patients and in animal models of this disorder. Several studies suggest that the hippocampus is an important area to be considered for apoptotic cell death. In our studies in the rat hippocampus, we have measured the expression of inducers and blockers of apoptosis in membrane, cytosolic and mitochondrial fractions, and the activity of caspases. The level of cytosolic Fas was increased in cholinergic denervation compared to control and hippocampal sympathetic ingrowth groups. The membrane Fas ligand expression was significantly increased in hippocampal sympathetic ingrowth and in cholinergic denervation compared to the control group. The level of caspase-3 (CPP32) was increased in the cholinergic denervation group compared to control and hippocampal sympathetic ingrowth groups. The cytosolic expression of bcl-x was increased in hippocampal sympathetic ingrowth compared to control and cholinergic denervation. The cytosolic activity of caspase-3 appeared to be significantly decreased in hippocampal sympathetic ingrowth and increased in cholinergic denervation groups compared to control and cholinergic denervation/hippocampal sympathetic ingrowth, respectively. From the present results, we suggest that cholinergic denervation may be responsible for pro-apoptotic responses, while hippocampal sympathetic ingrowth may protect neurons from apoptosis in rat dorsal hippocampus.
Assuntos
Apoptose/fisiologia , Caspases/metabolismo , Fibras Colinérgicas/metabolismo , Hipocampo/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/biossíntese , Plasticidade Neuronal/fisiologia , Gânglio Cervical Superior/crescimento & desenvolvimento , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Caspase 3 , Denervação/efeitos adversos , Proteína Ligante Fas , Hipocampo/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Vias Neurais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Núcleos Septais/metabolismo , Gânglio Cervical Superior/metabolismo , Proteína bcl-X , Receptor fas/metabolismoRESUMO
Following cholinergic denervation of the hippocampus by medial septal lesions, an unusual neuronal reorganization occurs in which peripheral adrenergic fibers arising from the superior cervical ganglia grow into the hippocampus (hippocampal sympathetic ingrowth). We have reported previously that cholinergic denervation and hippocampal sympathetic ingrowth differentially affected cholinergically stimulated phosphoinositide hydrolysis, concentration and affinity of muscarinic receptors, Go-protein level and protein kinase C activity. To complete these studies, we determined whether cholinergic denervation and hippocampal sympathetic ingrowth influenced phospholipase C and protein kinase C expression in dorsal hippocampal membranes and cytosol. Using immunoblotting methods, the results showed that the 100,000 mol. wt subunit of phospholipase Cbeta was increased in the membrane fraction in the hippocampal sympathetic ingrowth group by 45% compared to controls and the 150,000 mol.wt subunit was increased by 75% and 59% compared to controls and cholinergic denervation, respectively. For protein kinase C detection, immunoblots were prepared using antibodies selective for "classical" protein kinase C members (alpha, beta, gamma) and for the "novel" protein kinase C subfamily members (delta, θ). Membrane protein kinase Cbeta was decreased in hippocampal sympathetic ingrowth by 35% compared to controls and by 41% compared to cytosolic hippocampal sympathetic ingrowth. Membrane protein kinase Cbeta was decreased in cholinergic denervation by 28% compared to controls. When compared to membranes from controls and the cholinergic denervation group, and to cytosolic fractions from the hippocampal sympathetic ingrowth groups, respectively, the following membrane protein kinase isoforms were found to be decreased by hippocampal sympathetic ingrowth: gamma by 55%, 40% and 57%; delta by 91.5%, 70% and 120%; theta; by 95%, 100% and 86%.In conclusion, our results may indicate the connection between the previously reported differential influence of hippocampal sympathetic ingrowth and cholinergic denervation on cholinergically stimulated phosphoinositol hydrolysis. The "normalization" of phosphoinositol hydrolysis found in hippocampal sympathetic ingrowth may be due to the increase in phospholipase Cbeta expression in hippocampal sympathetic ingrowth membrane fractions. Since the activation of protein kinase C is known to block phosphoinositol hydrolysis, hippocampal sympathetic ingrowth "normalization" of phosphoinositol hydrolysis may result from a reduction in protein kinase expression in hippocampal sympathetic ingrowth membranes.
Assuntos
Hipocampo/metabolismo , Proteína Quinase C/metabolismo , Septo do Cérebro/metabolismo , Fosfolipases Tipo C/metabolismo , Animais , Membrana Celular/metabolismo , Citosol/metabolismo , Hipocampo/citologia , Masculino , Ratos , Ratos Sprague-Dawley , Septo do Cérebro/cirurgia , SimpatectomiaRESUMO
Following cholinergic denervation of the hippocampal formation, via medial septal lesions, peripheral noradrenergic fibers, originating from the superior cervical ganglion, grow into the hippocampus. In previous studies, we have found that hippocampal sympathetic ingrowth and cholinergic denervation alone (animals with concurrent medial septal lesions and superior cervical ganglionectomy) alter phosphoinositide turnover and muscarinic cholinergic receptors in such a way as to suggest an alteration in coupling between the muscarinic cholinergic receptors and phosphoinositol turnover. To test this hypothesis we examined the effect of hippocampal sympathetic ingrowth and cholinergic denervation on phospholipase C activity, G-protein function and the whole receptor complex by measuring the amount of phosphoinositide hydrolysed in hippocampal membranes of the rat. Neither hippocampal sympathetic ingrowth nor cholinergic denervation was found to alter phospholipase C activity when activated by increasing concentrations of Ca2+. In dorsal hippocampus, cholinergic denervation, when compared to hippocampal sympathetic ingrowth and controls, was found to decrease the amount of phosphoinositol hydrolysed when stimulated with the GTP analog, guanosine-5'-O-(3-thiotriphosphate). When guanosine-5'-O-(3-thiotriphosphate) plus carbachol (1 mM) was utilized to stimulate the entire receptor complex, phosphoinositol hydrolysis was found to be decreased in the cholinergic denervation group as compared to both hippocampal sympathetic ingrowth and control groups. This effect was maximum at 3 microM guanosine-5'-O-(3-thiotriphosphate). These results suggest that both hippocampal sympathetic ingrowth and cholinergic denervation affect the efficiency of coupling between the muscarinic cholinergic receptors and phosphoinositol turnover, with cholinergic denervation decreasing and hippocampal sympathetic ingrowth "normalizing" efficiency. Further, they suggest that the G-protein is the site at which hippocampal sympathetic ingrowth and cholinergic denervation mediate their effects. The results of these experiments are also discussed within the context of recent findings demonstrating G-protein abnormalities in Alzheimer's disease.
Assuntos
Fibras Adrenérgicas/fisiologia , Fibras Colinérgicas/fisiologia , Proteínas de Ligação ao GTP/fisiologia , Hipocampo/enzimologia , Fosfolipases Tipo C/metabolismo , Animais , Cálcio/farmacologia , Carbacol/farmacologia , Colina O-Acetiltransferase/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Hipocampo/química , Hipocampo/citologia , Hidrólise , Masculino , Parassimpatomiméticos/farmacologia , Fosfatidilinositóis/metabolismo , Fosfatidilinositóis/farmacologia , Ratos , Ratos Sprague-Dawley , Simpatectomia , TrítioRESUMO
Our laboratory has been utilizing the model of hippocampal sympathetic ingrowth, which has been suggested to occur in Alzheimer's disease, to investigate the effects of cholinergic denervation and hippocampal rearrangements. After cholinergic denervation by medial septal lesions, peripheral sympathetic fibres originating from the superior cervical ganglia grow into the rat hippocampus. This hippocampal sympathetic ingrowth can be prevented by superior cervical ganglionectomy. We examined the long-term effects of these treatments on muscarinic receptors by comparing [3H]quinuclidinyl benzilate binding in rat dorsal hippocampus four and 12 weeks post lesion. Four groups of animals were employed, including controls (sham lesion+sham ganglionectomy), animals with ingrowth (medial septal lesion+ sham ganglionectomy), animals with cholinergic denervation alone (medial septal lesion+ ganglionectomy), and ganglionectomy alone (sham lesion+ganglionectomy) animals. In dorsal hippocampus four weeks post lesion, binding affinity was similar among all groups, while muscarinic receptor number was increased in ingrowth animals as compared to both the control (P<0.0002) and ganglionectomy animals (P<0.01). By 12 weeks, receptor affinity was significantly decreased in ingrowth (P<0.0001) and cholinergic denervation (P<0.0003) groups, and receptor number remained significantly elevated in ingrowth animals as compared to control (P<0.01), ganglionectomy (P<0.02) and cholinergic denervation (P<0.01) groups. The decrease in muscarinic receptor affinity may provide some insight into the ineffectiveness of cholinomimetic therapies in Alzheimer's disease, in that agonist efficacy would be reduced at the receptor.
Assuntos
Hipocampo/metabolismo , Parassimpatectomia , Receptores Muscarínicos/metabolismo , Sistema Nervoso Simpático/fisiologia , Animais , Colina O-Acetiltransferase/metabolismo , Ganglionectomia , Hipocampo/citologia , Cinética , Masculino , Plasticidade Neuronal/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/efeitos dos fármacos , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/crescimento & desenvolvimentoRESUMO
OBJECTIVE: To describe the attitudes about adolescent health issues, especially school-based health services, held by adults in a rural community. DESIGN: "Before-after," quasi-experimental design involving independent, cross-sectional population-based surveys in 1989 and 1992. SETTING: Rural county located in the southeastern United States. PARTICIPANTS: Probability sample of adults, 18 years and older, who were residents of the county, including 831 respondents in the first survey and 210 respondents in the second survey. INTERVENTION: County-wide public education campaign involving public service announcements on television and radio, newspaper advertisements, posters, and open-to-the-public adolescent health programs and events. MAIN OUTCOME MEASURES: Attitudes about the types of health services that should be included in a public school-based adolescent health program. RESULTS: Rural adults' attitudes toward public school-based adolescent health services were similar before and after the community-wide campaign. Respondents believed the public schools should provide teenagers with information and counseling on substance abuse, sexual activity, birth control, and the acquired immunodeficiency syndrome but should not provide primary health care or birth control products. Most adults believed that sex and acquired immunodeficiency syndrome education should begin before high school. CONCLUSIONS: A comprehensive, public school-based adolescent health program providing health information but not health services may be acceptable to this community. Adults' attitudes about adolescent health issues do not appear to have been modified by the adolescent health awareness campaign.
Assuntos
Serviços de Saúde do Adolescente , Atitude Frente a Saúde , Serviços de Saúde Escolar , Comportamento Sexual , Adolescente , Comportamento do Adolescente , Adulto , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Opinião Pública , População Rural , Estados UnidosRESUMO
Electrolytic lesions of the medial septal region leads to an unusual neuronal reorganization in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the cholinergically denervated areas of the hippocampus. Since these lesions disrupt cells and fibers of passage which are non-cholinergic, there has been a debate whether Hippocampal Sympathetic Ingrowth is due only to cholinergic denervation of the hippocampus. Using the intraseptal administration of 192-IgG-Saporin, a specific cholinergic neurotoxin, we have found that hippocampal sympathetic ingrowth occurs in the cholinergically denervated hippocampus at 4, 8 and 12 weeks post Saporin injection. These results clearly suggest that hippocampal sympathetic ingrowth is due to the specific loss of the cholinergic projection from the medial septum.
Assuntos
Anticorpos Monoclonais/farmacologia , Fibras Colinérgicas/efeitos dos fármacos , Hipocampo/patologia , Imunotoxinas/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Fibras Simpáticas Pós-Ganglionares/patologia , Acetilcolina/metabolismo , Acetilcolinesterase/metabolismo , Animais , Comunicação Celular/fisiologia , Colinérgicos/farmacologia , Fibras Colinérgicas/patologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , N-Glicosil Hidrolases , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Regeneração Nervosa/fisiologia , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Plasticidade Neuronal/fisiologia , Neurotoxinas/farmacologia , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Inativadoras de Ribossomos Tipo 1 , Saporinas , Núcleos Septais/patologia , Núcleos Septais/fisiopatologia , Gânglio Cervical Superior/patologia , Gânglio Cervical Superior/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Fatores de TempoRESUMO
Phosphoinositide hydrolysis induced by norepinephrine, quisqualate, or trans-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), but not by carbachol, was approximately 50% greater in hippocampal slices from adrenalectomized (14 days) rats compared with controls. These changes appeared to be selective for the hippocampus because no effects of adrenalectomy on phosphoinositide hydrolysis were detected in cortical or striatal slices. The enhanced response to norepinephrine in hippocampal slices after adrenalectomy was observed throughout the effective concentration range of norepinephrine, was not influenced by in vitro addition of corticosterone, was not mimicked or altered by incubation with dibutyryl cyclic adenosine 3',5'-monophosphate (AMP), and did not appear to be due to impaired inhibition of the response to norepinephrine which was elicited by activation of protein kinase C or by inclusion of an inhibitory concentration of quisqualate. These findings indicate that adrenalectomy either removes an inhibitory influence of glucocorticoids on the phosphoinositide system in the hippocampus or that the neurodegeneration of granule cells in the dentate gyrus following adrenalectomy is associated with neurotransmitter-selective increases in phosphoinositide hydrolysis. These data provide further evidence that glucocorticoids modify signal transduction in the brain and extends their known influence to the phosphoinositide second messenger system.
Assuntos
Adrenalectomia , Aminoácidos/metabolismo , Hipocampo/metabolismo , Norepinefrina/farmacologia , Fosfatidilinositóis/metabolismo , Animais , Bucladesina/farmacologia , Hipocampo/efeitos dos fármacos , Hidrólise , Técnicas In Vitro , Masculino , Ácido Quisquálico/farmacologia , Ratos , Ratos EndogâmicosRESUMO
After cholinergic denervation of the hippocampus, via medial septal (MS) lesions, peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. In this study, we sought to determine the effect of hippocampal sympathetic ingrowth (HSI) on the M2 subtype of muscarinic cholinergic receptors, by examining the membrane binding of [3H]AF-DX 384 in hippocampal tissue from control rats, rats with HSI and rats with MS lesions + concurrent ganglionectomy (CD group). In dorsal hippocampus, Kd was found to be increased while Bmax was decreased in the CD group as compared with both the HSI and control group which did not differ from one another. In ventral hippocampus, Kd was found to be increased while Bmax was decreased in the CD group when compared only with the control group. These results suggest that sympathetic ingrowth, which has its greatest concentration in dorsal hippocampus, can 'normalize' the M2 receptor in hippocampus.
Assuntos
Fibras Colinérgicas/fisiologia , Hipocampo/fisiologia , Receptores Muscarínicos/fisiologia , Animais , Ligação Competitiva , Denervação , Masculino , Ratos , Ratos Sprague-Dawley , Sistema Nervoso SimpáticoRESUMO
Hippocampal sympathetic ingrowth (HSI), a form of neuronal plasticity, is induced by medial septal lesions and consists of the sprouting of peripheral sympathetic fibers, arising from the superior cervical ganglion, into the dentate gyrus and CA3 region of the hippocampus. HSI has been previously shown to alter learned and spontaneous behaviors, phosphatidyl inositide hydrolysis, and the antagonist binding kinetics of both muscarinic cholinergic receptors and phorbol ester receptors. We now report that sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C (PKC) following septohippocampal denervation of the rat hippocampus. Further, no changes were found in alpha, beta or gamma PKC isoenzymes among experimental groups, suggesting that the group A PKC isoforms do not mediate the observed changes in activity and phorbol ester binding.
Assuntos
Denervação , Hipocampo/fisiologia , Fibras Nervosas/fisiologia , Plasticidade Neuronal , Proteína Quinase C/metabolismo , Sistema Nervoso Simpático/fisiologia , Análise de Variância , Animais , Western Blotting , Membrana Celular/enzimologia , Giro Denteado/fisiologia , Hipocampo/enzimologia , Isoenzimas/metabolismo , Masculino , Células Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley , Gânglio Cervical Superior/fisiologiaRESUMO
Diazepam increased the acetylcholine content in the striatum and the hippocampus of the rat. This effect was antagonized in both brain areas by treatment with the specific central benzodiazepine blockers ethyl-beta-carboline-3-carboxylate and Ro 15-1788, whereas the peripheral antagonist Ro 5-4864 was ineffective. Pretreatment with picrotoxin, a known GABA antagonist did not interfere with the diazepam-induced acetylcholine increase. These results indicate a specific involvement of benzodiazepine receptors in the cholinergic action of diazepam and this effect appears to be independent of GABA receptor activation.
Assuntos
Acetilcolina/biossíntese , Benzodiazepinonas/farmacologia , Carbolinas/farmacologia , Corpo Estriado/efeitos dos fármacos , Diazepam/farmacologia , Indóis/farmacologia , Animais , Benzodiazepinas/antagonistas & inibidores , Química Encefálica/efeitos dos fármacos , Corpo Estriado/metabolismo , Feminino , Flumazenil , Ratos , Ratos Endogâmicos , Receptores de GABA-ARESUMO
Following cholinergic denervation of the hippocampus by medial septal lesions, and unusual neuronal reorganization occurs, in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. Previously, we have found that both hippocampal sympathetic ingrowth (HSI) and cholinergic denervation (CD), alone, altered the total number and affinity of muscarinic cholinergic receptors (mAChR). In this study, we utilized the muscarinic antagonist [3H]Pirenzepine, in combination with membrane radioligand binding techniques, to determine the effects of HSI and CD on hippocampal M1 and M1 + M3 mAChR subtypes, 4 weeks after MS lesions. In both the dorsal and ventral hippocampus, HSI was found to markedly diminish the number of M1 AChRs, while CD was found to increase the number of M1 AChRs. Neither treatment affected the affinity of the M1 AChR. However, when M1 + M3 binding was assessed, CD was found to decrease the affinity in both hippocampal regions, without altering the number of receptors. Neither affinity nor number of M1 + M3 receptors was altered by HSI. The results of this study suggest that both cholinergic denervation and hippocampal sympathetic ingrowth uniquely affect hippocampal muscarinic receptors.
Assuntos
Acetilcolina/fisiologia , Hipocampo/fisiologia , Receptores Muscarínicos/metabolismo , Gânglio Cervical Superior/fisiologia , Análise de Variância , Animais , Denervação , Hipocampo/metabolismo , Masculino , Fibras Nervosas/fisiologia , Pirenzepina/metabolismo , Quinuclidinil Benzilato/metabolismo , Ensaio Radioligante , Ratos , Ratos Sprague-DawleyRESUMO
Following cholinergic denervation of the hippocampus by medial septal (MS) lesions, an unusual neuronal reorganization occurs in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus (hippocampal sympathetic ingrowth; HSI). Previously, we have found that with MS lesions, animals with (the HSI(+) group) and without (HSI(-) group) ingrowth differed in carbachol stimulated PI hydrolysis, in PKC activity, and in muscarinic cholinergic receptors (mAChR). In this study, performed in hippocampal slices obtained four weeks after MS lesions, we utilized the hydrophilic muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) and hydrophobic muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB) in the presence of either 4-alpha-phorbol or phorbol 12,13-dibutyrate (PDBu) to determine the effect of MS lesions with and without ingrowth on PKC-mediated mAChR internalization. In the presence of PDBu, a group effect was observed in [3H]NMS binding, with control groups > HSI(+) group > HSI(-) group. However, [3H]QNB binding was similar across groups. These results suggest that the cholinergic denervation of the hippocampus enhances the internalization of mAChRs, which is modified in the presence of HSI.
Assuntos
Acetilcolina/fisiologia , Hipocampo/fisiologia , Receptores Muscarínicos/metabolismo , Gânglio Cervical Superior/fisiologia , Animais , Denervação , Regulação para Baixo/efeitos dos fármacos , Hipocampo/metabolismo , Técnicas In Vitro , Masculino , N-Metilescopolamina , Fibras Nervosas/fisiologia , Neurônios/fisiologia , Dibutirato de 12,13-Forbol/farmacologia , Quinuclidinil Benzilato/metabolismo , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Derivados da Escopolamina/metabolismoRESUMO
Tiaspirone, a potential antipsychotic drug, reduced the acetylcholine content of rat hemispheric brain regions (striatum 35%, hippocampus 20%, cortex 32% with no effect on N. accumbens) at an oral dose of 40 mg/kg. Choline content was uniformly raised in the same brain regions. A kinetic study showed that the drug is evenly distributed in the brain. Tiaspirone's effects on acetylcholine and choline in the striatum were not related in time. The fall off (30-240 min) of tiaspirone's effect on choline content paralleled the decline in striatal drug concentration (t1/2 = 240 min) whereas that on acetylcholine did not. No tolerance was observed to an acute challenge with tiaspirone on acetylcholine and choline in the striatum after 11 days' subchronic treatment. In vitro the drug had no effect on striatal choline acetyltransferase and acetylcholinesterase activities up to a concentration of 300 microM. The muscarinic agonist oxotremorine did not interfere with the acetylcholine decrease produced by the drug suggesting that muscarinic receptors are not essential for this effect. Tiaspirone, however, was found to be a competitive, reversible inhibitor of the sodium-dependent high-affinity choline uptake (SDHACU) by crude hippocampal and striatal synaptosomal preparations, giving IC50 values of respectively 3.69 microM and 1.14 microM. The compound did not alter SDHACU ex vivo despite the fact that it readily crosses the blood-brain barrier and achieves brain concentrations equivalent to its in vitro IC50 concentration. Tiaspirone antagonized the striatal acetylcholine increasing effect of apomorphine, a selective dopaminergic receptor agonist, supporting the idea that the drug affects the striatal cholinergic system by a primary action on dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)