RESUMO
BACKGROUND/AIM: Few studies have specifically investigated treatment of prednisolone-induced hyperglycaemia. AIM: To determine if a basal bolus insulin (BBI) protocol for inpatient hyperglycaemia is effective in patients prescribed acute prednisolone for an inflammatory disease. METHODS: In a cross-sectional study, 66 patients with type 2 diabetes admitted to a general medical ward and treated with BBI for up to 5 days were studied. Twenty-four patients were taking prednisolone ≥10 mg/day to treat an acute inflammatory disease. The remaining 42 patients were a control group. The primary outcome was mean daily blood glucose level. RESULTS: There were no significant differences in glycosylated haemoglobin (8.1 ± 1.0 vs 8.1 ± 1.6%, P = 0.88), age (77 ± 11 vs 75 ± 14 years, P = 0.57), male sex (63 vs 60%, P = 0.81) or body mass index (30.0 ± 5.3 vs 30.2 ± 11.5 kg/m(2) , P = 0.90) between patients taking prednisolone and controls. Mean daily glucose concentration was higher in patients taking prednisolone than in controls (12.2 ± 0.3 vs 10.0 ± 0.1 mmol/L, P < 0.001). Blood glucose level was higher in patients on prednisolone at 1700 h (14.6 ± 0.6 vs 10.3 ± 0.3 mmol/L, P < 0.001) and 2100 h (14.5 ± 0.6 vs 10.5 ± 0.3 mmol/L, P < 0.001), with no significant differences at 0700 h and 1200 h. These findings occurred despite patients taking prednisolone receiving a higher daily insulin dose than controls (0.67-0.70 vs 0.61-0.65 U/kg, P = 0.001) because of higher doses of ultra-rapid-acting insulin at 1200 h and 1700 h. CONCLUSIONS: Hospitalised patients taking prednisolone had substantial afternoon and evening hyperglycaemia despite receiving BBI via a protocol for inpatient hyperglycaemia. Specific insulin regimens for prednisolone-induced hyperglycaemia are needed that recommend more insulin during this time period.
Assuntos
Hospitalização , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Insulina/administração & dosagem , Prednisolona/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Glucocorticoides/efeitos adversos , Humanos , Hiperglicemia/sangue , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
We have assessed whether glucose concentration and patient outcome are related in hospitalised patients when glycaemia is quantified in detail. Continuous glucose monitoring was performed on 47 consecutive subjects with an acute exacerbation of chronic obstructive pulmonary disease. Length of hospital stay increased by 10% for each mmol/L increase in mean glucose (P = 0.01). In a multivariable analysis, mean glucose was independently associated with length of hospital stay (P = 0.02). These data add weight to evidence that hyperglycaemia may adversely affect patient outcomes in hospitalised patients.
Assuntos
Glicemia/metabolismo , Índice Glicêmico/fisiologia , Tempo de Internação/tendências , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
Deposition of amyloid beta-protein (A beta) in the brain plays a key role in the pathogenesis of Alzheimer's disease. Apolipoprotein E epsilon 4 allele (apo E-epsilon 4) is a strong risk factor for Alzheimer's disease, and there is in vitro evidence that apo E is directly involved in A beta deposition. Head injury is an epidemiological risk factor for Alzheimer's disease and deposition of A beta occurs in approximately one-third of individuals dying after a severe head injury. We report here that the frequency of apo E-epsilon 4 in those individuals with A beta deposition following head injury (0.52) is higher than in most studies of Alzheimer's disease, while in those head-injured individuals without A beta deposition the apo E-epsilon 4 frequency (0.16) is similar to controls without Alzheimer's disease (P < 0.00001). This finding provides further evidence linking apo E-epsilon 4 with A beta deposition in vivo and suggests that known environmental and genetic risk factors for Alzheimer's disease may act additively. In addition our finding indicates a genetic susceptibility to the effects of a head injury.
Assuntos
Peptídeos beta-Amiloides/análise , Apolipoproteínas E/genética , Córtex Cerebral/química , Traumatismos Craniocerebrais/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Alelos , Doença de Alzheimer/etiologia , Apolipoproteína E4 , Córtex Cerebral/patologia , Traumatismos Craniocerebrais/patologia , Dosagem de Genes , Frequência do Gene , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases, the most studied, but still unidentified ones, are those involved in the release of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma-secretase is the last processing step resulting in release of A beta. Cleavage occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42 [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus generally believed that inhibition of this enzyme could aid in prevention of AD. Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site for A beta(1-40) generation. It is interesting that intracellular generation of A beta seemed to be unique to neurons, because we found that nonneuronal cells produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell surface. The specific production of the critical A beta isoform in the ER of neurons links this compartment with the generation of A beta and explains why primarily ER localized (mutant) proteins such as the presenilins could induce AD. We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/biossíntese , Fragmentos de Peptídeos/biossíntese , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide , Animais , Ácido Aspártico Endopeptidases , Células COS , Compartimento Celular , Membrana Celular/metabolismo , Endopeptidases/metabolismo , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Humanos , Microscopia Imunoeletrônica , Neurônios/metabolismo , Neurônios/ultraestrutura , RatosRESUMO
Prion diseases in humans show considerable clinical and pathological heterogeneity. The identification of a new variant of Creutzfeldt-Jakob disease, and its interpretation as evidence of transmission of mad cow disease to man, rely critically on our understanding of the epidemiology of prion diseases.
Assuntos
Síndrome de Creutzfeldt-Jakob , Encefalopatia Espongiforme Bovina/transmissão , Adulto , Animais , Bovinos , Humanos , Pessoa de Meia-Idade , Doenças Priônicas/etiologia , PríonsRESUMO
Recent prospective studies indicate that schizophrenia manifests itself in behavioural abnormalities much earlier than was previously thought, supporting the view that schizophrenia is a developmental disorder.
Assuntos
Neurônios , Esquizofrenia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Humanos , Neurônios/patologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologiaRESUMO
Structural abnormalities are found in the brains of schizophrenics. They affect preferentially, but not exclusively, medial temporal lobe structures (parahippocampal gyrus, hippocampus and amygdala), and can be found in all sub-types of schizophrenia. The structures of the medial temporal lobe are believed to have a crucial role in the integration and processing of the output from association cortex. It is probable that all schizophrenics have abnormalities in the medial temporal lobe that differ in degree but not in kind. Dysfunction of this system could result in the clinical symptoms that form the core of the schizophrenia syndrome. The changes in brain structure are not the result of neurodegenerative processes or destructive lesions but suggest a disturbance in the normal pattern of brain development.
Assuntos
Esquizofrenia/patologia , Lobo Temporal/patologia , Humanos , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologiaRESUMO
Schizophrenia is associated with structural changes (eg, a mild degree of ventricular enlargement) in the brain, although whether these precede onset of illness or progress with episodes is not established. In a postmortem study, we find that ventricular enlargement affects the posterior and particularly the temporal horn of the lateral cerebral ventricle. By comparison with controls and with patients suffering from Alzheimer-type dementia (in which there is also temporal horn enlargement), the change is highly significantly selective to the left hemisphere. This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique). The findings are consistent with the view that schizophrenia is a disorder of the genetic mechanisms that control the development of cerebral asymmetry.
Assuntos
Encéfalo/patologia , Lateralidade Funcional , Esquizofrenia/patologia , Doença de Alzheimer/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Ventrículos Cerebrais/crescimento & desenvolvimento , Ventrículos Cerebrais/patologia , Ventriculografia Cerebral , Feminino , Lateralidade Funcional/genética , Gliose/patologia , Humanos , Masculino , Esquizofrenia/genéticaRESUMO
The histologically apparent polymorphism of plaques containing beta-amyloid in Alzheimer's disease is thought to represent different stages in plaque evolution. beta-amyloid-immunopositive plaques were classified according to the pattern of beta-amyloid distribution (diffuse vs dense-core) and the presence or absence of dystrophic beta-amyloid precursor protein-immunopositive (beta-APP+) neurites (neuritic vs non-neuritic). The potential contribution of microglia-derived interleukin-1 (IL-1), an immune response cytokine that induces synthesis and processing of beta-APP, to the possible sequential development of these plaque types was examined through determination of the number of IL-1 alpha+ microglia associated with each of four identified plaque types. Diffuse non-neuritic plaques had the least dense and most widely dispersed beta-amyloid, did not exhibit beta-APP+ dystrophic neurites, but most (78%) contained activated IL-1 alpha+ microglia (2 +/- 0.2/plaque; mean +/- SEM). Diffuse neuritic plaques had more dense, but still widely dispersed beta-amyloid, displayed a profusion of beta-APP+ dystrophic neurites, and had the greatest numbers of associated activated IL-1 alpha+ microglia (7 +/- 0.8/plaque). Dense-core neuritic plaques had both compact and diffuse beta-amyloid and had fewer IL-1 alpha+ microglia (4 +/- 0.4/plaque). Dense-core, non-neuritic plaques had compact beta-amyloid, lacked associated diffuse beta-amyloid, and were devoid of both IL-1 alpha+ microglia and beta-APP+ dystrophic neurites. These results suggest an important immunological component in the evolution of amyloid-containing plaques in Alzheimer's disease and further suggest that IL-1-expressing cells are necessary to initiate dystrophic neurite formation in diffuse beta-amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença de Alzheimer/patologia , Interleucina-1/análise , Lobo Temporal/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/imunologia , Autopsia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Lobo Temporal/imunologiaRESUMO
Synaptophysin immunoreactivity can be quantified by image analysis to evaluate loss of presynaptic terminals in human neurodegenerative diseases. The extent and regional distribution of such loss is reported in motor neuron disease (MND). Autopsy samples of spinal cord and cerebral cortex were examined from 28 cases of MND and 28 age and sex matched controls. The MND group included individuals with amyotrophic lateral sclerosis (17[ALS]), and progressive muscular atrophy (11[PMA]). In the spinal cord, there was significant reduction of presynaptic terminals in the lateral ventral horn (15%) in both the ALS (p < 0.01) and PMA (p < 0.05) groups. Perisomatic synaptophysin profiles on lower motor neurons are preserved late in the disease and are not related to corticospinal innervation. Less marked presynaptic loss was demonstrable more widely in the medial ventral, intermediate and dorsal spinal grey matter (10%) in both ALS (p = 0.03) and PMA (p = 0.05). In the cerebral cortex no synaptic loss was demonstrated in motor or anterior cingulate regions in any of the MND cases. Spinal degeneration in MND is associated with loss of presynaptic terminals in all grey matter regions. It is most marked in the limb motor neuron area and is independent of corticospinal tract degeneration. The cerebral pathology of ALS is not associated with significant loss of presynaptic terminals in the cortical areas studied.
Assuntos
Esclerose Lateral Amiotrófica/patologia , Córtex Cerebral/patologia , Doença dos Neurônios Motores/patologia , Medula Espinal/patologia , Sinaptofisina/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Substância Cinzenta Periaquedutal/patologiaRESUMO
The role of glial inflammatory processes in Alzheimer's disease has been highlighted by recent epidemiological work establishing head trauma as an important risk factor, and the use of anti-inflammatory agents as an important ameliorating factor, in this disease. This review advances the hypothesis that chronic activation of glial inflammatory processes, arising from genetic or environmental insults to neurons and accompanied by chronic elaboration of neuroactive glia-derived cytokines and other proteins, sets in motion a cytokine cycle of cellular and molecular events with neurodegenerative consequences. In this cycle, interleukin-1 is a key initiating and coordinating agent. Interleukin-1 promotes neuronal synthesis and processing of the beta-amyloid precursor protein, thus favoring continuing deposition of beta-amyloid, and activates astrocytes and promotes astrocytic synthesis and release of a number of inflammatory and neuroactive molecules. One of these, S100beta, is a neurite growth-promoting cytokine that stresses neurons through its trophic actions and fosters neuronal cell dysfunction and death by raising intraneuronal free calcium concentrations. Neuronal injury arising from these cytokine-induced neuronal insults can activate microglia with further overexpression of interleukin-1, thus producing feedback amplification and self-propagation of this cytokine cycle. Additional feedback amplification is provided through other elements of the cycle. Chronic propagation of this cytokine cycle represents a possible mechanism for progression of neurodegenerative changes culminating in Alzheimer's disease.
Assuntos
Doença de Alzheimer/patologia , Citocinas/fisiologia , Inflamação/fisiopatologia , Neuroglia/citologia , Neurônios/citologia , Comunicação Celular/fisiologia , Progressão da Doença , Humanos , Fatores de RiscoRESUMO
Schizophrenia-like psychoses occur more frequently than expected in patients with chronic temporal lobe epilepsy. We have analyzed pathological and clinical data from a series (n = 249) of temporal lobectomies to determine the factors that may relate to the development of schizophrenia-like psychosis. Schizophrenia-like psychoses did not occur at random; they were significantly associated with lesions that (1) originated in the fetus or perinatally, (2) affected neurons in the medial temporal lobe, and (3) gave an early age of first fit. Gangliogliomas--developmental lesions of the medial temporal lobe containing aberrant neurons--were disproportionately (p less than 0.001) associated with risk of psychosis. Schizophrenia-like psychoses arising preoperatively occurred more often (p = 0.1) with left-sided lesions. Asymmetry of lesion was not present in cases with postoperative psychoses. These findings are of interest in relation to recent studies suggesting that the structural abnormalities found in the brains of schizophrenics arise during fetal brain development.
Assuntos
Epilepsia do Lobo Temporal/patologia , Transtornos Neurocognitivos/patologia , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Adulto , Mapeamento Encefálico , Delusões/patologia , Dominância Cerebral/fisiologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Alucinações/patologia , Humanos , Masculino , Neuroglia/patologia , Neurônios/patologia , Psicocirurgia , Lobo Temporal/cirurgia , Pensamento/fisiologiaRESUMO
Increased gliosis has been previously described in schizophrenic brain. In this study, the degree of gliosis in schizophrenic and control brains was assessed quantitatively using an antibody to glial fibrillary acidic protein, immunocytochemical techniques, and a computed image analysis system. Twenty separate brain areas were assessed, and no significant differences were found between the schizophrenic and control groups. It seems unlikely that a specific pattern of pathologically significant gliosis is present in schizophrenic brains. These negative findings are of note because of previously reported structural differences in the temporal lobe in the schizophrenic group in this series.
Assuntos
Encéfalo/patologia , Esquizofrenia/patologia , Adulto , Idoso , Atrofia , Encéfalo/metabolismo , Computadores , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Gliose , Humanos , Doença de Huntington/patologia , Masculino , Pessoa de Meia-Idade , Esquizofrenia/metabolismo , Tomografia Computadorizada por Raios XRESUMO
Recent studies have described two indicators of pathology in the schizophrenic brain--gliosis and atrophy. The degree of gliosis in the temporal lobe of groups of schizophrenics (with demonstrable atrophy), affectives, and controls was quantified using immunocytochemical techniques and computer-assisted densitometry. Twenty areas within the temporal lobe were assessed. Our data showed no evidence of increased gliosis in the schizophrenic group compared to controls and affectives. This extends and replicates our previous findings, demonstrating that the atrophy/aplasia in schizophrenia is not associated with pathologically significant gliosis. Our observations are consistent with other studies, suggesting that the structural change in schizophrenic brains is due to an embryonic insult or developmental anomaly of an, as yet, undetermined nature.
Assuntos
Gliose/patologia , Transtornos Neurocognitivos/patologia , Esquizofrenia/patologia , Lobo Temporal/patologia , Idoso , Atrofia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/patologia , Tomografia Computadorizada por Raios XRESUMO
Chronic overexpression of the neurite growth-promoting factor S100beta has been implicated in the pathogenesis of neuritic plaques in Alzheimer's disease. Such plaques are virtually universal in middle-aged Down's syndrome, making Down's a natural model of Alzheimer's disease. We determined numbers of astrocytes overexpressing S100beta, and of neurons overexpressing beta-amyloid precursor protein (beta-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down's syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100beta-immunoreactive (S100beta+) astrocytes in Down's patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down's patients. The numbers of S100beta+ astrocytes in young and adult Down's patients correlated with the numbers of neurons overexpressing beta-APP (p < 0.05). Our findings are consistent with the idea that conditions--including Down's syndrome--that promote chronic overexpression of S100beta may confer increased risk for later development of Alzheimer's disease.
Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Síndrome de Down/metabolismo , Proteínas S100/biossíntese , Adulto , Fatores Etários , Idoso , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Astrócitos/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Química Encefálica , Contagem de Células , Criança , Pré-Escolar , Síndrome de Down/patologia , Feto/química , Feto/metabolismo , Humanos , Lactente , Pessoa de Meia-Idade , Neurônios/química , Neurônios/patologia , Proteínas S100/análise , Proteínas tau/análiseRESUMO
The distribution of pancreastatin immunoreactivity was investigated in porcine brain, spinal cord, dorsal root ganglia, and pituitary. In the brain, immunoreactive cell bodies were present in many areas including the cortex, basal ganglia, hippocampus, thalamus, hypothalamus, mesencephalic reticular formation, cerebellum, and medulla oblongata. Immunoreactive fibres were most abundant in the globus pallidus, stria terminalis, entopeduncular nucleus, hippocampus, and in the substantia nigra. In the spinal cord, immunoreactive cells were found in laminae IV-IX. Immunoreactive fibres were concentrated in the dorsal horn. Pancreastatin immunoreactivity was localised to fibres and small cells (5-10% of the total) in the dorsal root ganglia. In the posterior pituitary, many immunoreactive fibres were present and in the anterior lobe subsets of gonadotrophs and thyrotrophs were pancreastatin-immunoreactive. The localisation of pancreastatin showed a parallel distribution with chromogranin A. Coexistence of pancreastatin with calcitonin gene-related peptide (CGRP) immunoreactivity in cell bodies in the spinal cord, including motoneurones, and with CGRP or galanin immunoreactivities in dorsal root ganglion cells was also noted. The differential pattern of pancreastatin immunostaining was reflected in the extractable levels of peptide with highest concentrations in the cortex (55.8 +/- 6.0 pmol/g wet weight, mean +/- S.E.M.), thalamus (60.0 +/- 5.0 pmol/g), hypothalamus (54.4 +/- 6.5 pmol/g), and anterior pituitary (2,714 +/- 380 pmol/g). Characterisation of pancreastatin immunoreactivity in the hypothalamus and pituitary by gel permeation and high-pressure liquid chromatography revealed multiple molecular forms, one of which was indistinguishable from natural porcine pancreastatin. The widespread distribution of pancreastatin immunoreactivity suggests this peptide may play a part in several neuroendocrine, autonomic, somatic, and sensory functions, and its colocalisation with chromogranin A is consistent with a precursor-product relationship.
Assuntos
Sistema Nervoso Central/metabolismo , Cromograninas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Hormônios Pancreáticos/metabolismo , Hipófise/metabolismo , Suínos/metabolismo , Animais , Animais Recém-Nascidos , Sistema Nervoso Central/citologia , Cromogranina A , Imuno-Histoquímica , Hipófise/citologiaRESUMO
The amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from Alzheimer's disease (AD) and Down's syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD). Using monoclonal antibodies to a synthetic peptide corresponding to a portion of beta-protein and rabbit antiserum to hamster scrapie PrP 27-30, we examined in situ amyloid plaques on sections from cases of neurodegenerative diseases, including cases with a spectrum of plaque types. Anti-beta-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases. Anti-PrP stained plaques in CJD, kuru, and Gerstmann-Sträussler syndrome cases but not cerebrovascular amyloid or plaques in AD. Dual localization experiments showed that in cases with a mixture of plaque types, the antibodies identified different populations of plaques that showed anatomic heterogeneity. Colocalization of the two proteins was not observed in any plaque type. The data suggest that in neurodegenerative diseases two major plaque types exist, which have different etiologic origins. Our results emphasize the need for classification of CNS amyloids based not on their morphology but on the macromolecular components comprising these pathologic polymers.
Assuntos
Doença de Alzheimer/metabolismo , Amiloide/análise , Química Encefálica , Síndrome de Creutzfeldt-Jakob/metabolismo , Medula Espinal/análise , Proteínas Virais/análise , Peptídeos beta-Amiloides , Humanos , Imuno-Histoquímica , Neurofibrilas/análise , Proteína PrP 27-30 , Doenças por Vírus Lento/metabolismoRESUMO
Nitric oxide is a free radical which is produced in the brain and is thought to be the first of a new class of neural messenger molecules. It is postulated to act by inducing an increase in cyclic guanosine monophosphate levels in target cells. The neuronal isoform of nitric oxide synthase, the enzyme responsible for the calcium-dependent synthesis of nitric oxide from L-arginine, has been purified from brain homogenate. Using a specific polyclonal antibody, we have localized brain nitric oxide synthase to the cytosol of discrete neuronal subpopulations and glial elements. These include non-pyramidal cells in the cerebral cortex, pyramidal and non-pyramidal cells of the hippocampus, aspiny neurons of the corpus striatum, basket, Purkinje and granule cells in the cerebellum and neurons of various brain stem nuclei. The localization of nitric oxide-producing neurons in morphologically different and neurochemically diverse cell types suggests a widespread neuromodulatory role for nitric oxide in the central nervous system of man.
Assuntos
Aminoácido Oxirredutases/análise , Encéfalo/enzimologia , Neurônios/enzimologia , Adulto , Encéfalo/anatomia & histologia , Humanos , Imuno-Histoquímica/métodos , Isoenzimas/análise , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase , Especificidade de Órgãos , Valores de ReferênciaRESUMO
The distribution of the neuropeptides vasoactive intestinal polypeptide, cholecystokinin octapeptide, substance P, neurotensin, methionine-enkephalin and somatostatin has been mapped immunocytochemically in the bed nucleus of the stria terminalis, one of the major sites of termination for efferent projections from the amygdala. Immunoreactive fibres and terminals were distributed more or less topographically and largely in accordance with the previously described localization of peptide-containing cell bodies in the amygdala and the amygdaloid projection fields in the bed nucleus as described by neuroanatomical techniques. Thus, vasoactive intestinal polypeptide, which was found in some of the lateral amygdaloid nuclei, had a substantial projection to the lateral bed nucleus. The lateral bed nucleus also contained cholecystokinin-octapeptide, substance P, neurotensin and methionine-enkephalin immunoreactivity which probably derived from the central amygdaloid nucleus, whilst cholecystokinin-octapeptide, and especially substance P-containing fibres, were found in the medial bed nucleus and probably arise from cells in the medial amygdala. Reciprocal amygdalopetal projections were suggested by the presence of substance P- and somatostatin-containing cell bodies in the mediodorsal bed nucleus and vasoactive intestinal polypeptide cells in the lateral bed nucleus, but somatostatin otherwise had a widespread distribution. Numerous local peptidergic connections were also noted both within the bed nucleus and between it and adjacent structures, especially the preoptic area, hypothalamus and the basal ganglia. These data provide further evidence that neuropeptides play a major role in the connectivity of the limbic system and show that the bed nucleus of the stria terminalis is an important relay station, particularly between amygdaloid efferents and other forebrain areas.
Assuntos
Núcleo Caudado/análise , Sistema Límbico/análise , Sistema Nervoso/metabolismo , Peptídeos/análise , Área Pré-Óptica/análise , Ratos/fisiologia , Septo Pelúcido/análise , Animais , Técnicas Imunoenzimáticas , Masculino , Distribuição TecidualRESUMO
The distribution of six neuropeptides (vasoactive intestinal polypeptide, cholecystokinin octapeptide, substance P, neurotensin, methionine-enkephalin and somatostatin) has been mapped in the amygdala using immunocytochemical methods. Cell bodies containing each peptide showed a differential distribution throughout the various subnuclei. Large numbers of vasoactive intestinal polypeptide and cholecystokinin-octapeptide-containing cell bodies were located in the lateral and cortical nuclei respectively, neurotensin-and methionine enkephalin-containing cell bodies in the central nucleus, and substance P-containing cell bodies primarily in the medial nucleus. Somatostatin-containing cell bodies were found in all nuclei. Neuropeptide-containing fibres were also differentially distributed. Substance P and cholecystokinin fibres formed dense plexuses in the medial nucleus whilst the greatest concentration of vasoactive intestinal polypeptide, neurotensin and methionine enkephalin fibres were seen in the central nucleus. Close observation of serial sections showed that all the neuropeptides studied had extensive intra-amygdaloid pathways and connections with other brain areas. The central nucleus and stria terminalis have particular importance in the organisation of peptides within the amygdala. The central nucleus acts as a focus for a number of converging/diverging peptide pathways and incoming catecholaminergic afferents. The stria terminalis contains all six peptides and represents the major efferent peptidergic system. The amygdala is thought to control a number of endocrine responses and to regulate complex behavioural functions. The abundance of neuropeptides within the amygdala and their complex pattern imply that they may act to regulate endocrine responses to external events (e.g. stress) or alter emotional tone functions thought to be controlled by the amygdala.