RESUMO
Mammalian neurons can synthesize choline by methylating phosphatidylethanolamine and hydrolyzing the resulting phosphatidylcholine. This process is stimulated by catecholamines. The phosphatidylethanolamine is synthesized in part from phosphatidylserine; hence the amino acids methionine (acting after conversion to S-adenosylmethionine) and serine can be the ultimate precursors of choline. Brain choline concentrations are generally higher than plasma concentrations, but depend on plasma concentrations because of the kinetic characteristics of the blood-brain-barrier transport system. When cholinergic neurons are activated, acetylcholine release can be enhanced by treatments that increase plasma choline (for example, consumption of certain foods).
Assuntos
Colina/fisiologia , Fibras Colinérgicas/fisiologia , Acetilcolina/análise , Acetilcolina/biossíntese , Acetilcolina/fisiologia , Animais , Barreira Hematoencefálica , Química Encefálica/efeitos dos fármacos , Colina/biossíntese , Colina/metabolismo , Colina/farmacologia , Colina O-Acetiltransferase/fisiologia , Fibras Colinérgicas/metabolismo , Metiltransferases/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolamina N-Metiltransferase , RatosRESUMO
Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.
Assuntos
Proteínas Morfogenéticas Ósseas/fisiologia , Proteínas de Membrana Transportadoras , Proteínas de Transporte Vesicular , Acetilcolina/biossíntese , Animais , Proteínas de Transporte/genética , Células Cultivadas , Sistema Nervoso Central , Colina O-Acetiltransferase/genética , Embrião de Mamíferos/metabolismo , Fator 2 de Crescimento de Fibroblastos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Fator 2 de Diferenciação de Crescimento , Camundongos , Neurônios/metabolismo , Fenótipo , RNA Mensageiro/metabolismo , Septo do Cérebro/embriologia , Septo do Cérebro/metabolismo , Medula Espinal/embriologia , Medula Espinal/metabolismo , Regulação para Cima , Proteínas Vesiculares de Transporte de AcetilcolinaRESUMO
Choline is an essential nutrient for rats and humans, and its availability during fetal development has long-lasting cognitive effects (Blusztajn, 1998). We investigated the effects of prenatal choline supplementation on memory deficits associated with status epilepticus. Pregnant rats received a control or choline-supplemented diet during days 11-17 of gestation. Male offspring [postnatal day 29 (P29)-32] were tested for their ability to find a platform in a water maze before and after administration of a convulsant dose of pilocarpine at P34. There were no differences between groups in water maze performance before the seizure. One week after status epilepticus (P41-P44), animals that had received the control diet prenatally had a drastically impaired performance in the water maze during the 4 d testing period, whereas prenatally choline-supplemented rats showed no impairment. Neither the seizures nor the prenatal availability of choline had any effect on hippocampal choline acetyltransferase or acetylcholinesterase activities. This study demonstrates that prenatal choline supplementation can protect rats against memory deficits induced by status epilepticus.
Assuntos
Colina/farmacologia , Suplementos Nutricionais , Transtornos da Memória/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Estado Epiléptico/complicações , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/patologia , Contagem de Células , Colina/metabolismo , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Pilocarpina , Gravidez , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Estado Epiléptico/induzido quimicamenteRESUMO
A new assay procedure for measurement of rat liver mitochondrial choline dehydrogenase was developed. Oxidation of [methyl-14C]choline to [methyl-14C]betaine aldehyde and [methyl-14C]betaine was measured after isolating these compounds using HPLC. We observed that NAD+ was required for conversion of betaine aldehyde to betaine in rat liver mitochondria. In the absence of this cofactor, oxidation of choline led to the accumulation of betaine aldehyde. The apparent Km of the mitochondrial choline dehydrogenase for choline was 0.14-0.27 mM, which is significantly lower than previously reported. A partially purified preparation of choline dehydrogenase catalyzed betaine aldehyde formation only in the presence of exogenous electron acceptors (e.g., phenazine methosulfate). This preparation failed to catalyze the formation of betaine even in the presence of NAD+, indicating that betaine aldehyde dehydrogenase may be a separate enzyme from choline dehydrogenase.
Assuntos
Betaína/análogos & derivados , Betaína/metabolismo , Colina/metabolismo , Mitocôndrias Hepáticas/metabolismo , Oxirredutases do Álcool/metabolismo , Animais , Colina Desidrogenase , Cromatografia Líquida de Alta Pressão/métodos , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley , SolubilidadeRESUMO
Sphingoid bases are precursors and breakdown products of sphingolipids and may function as second messengers. Here we have tested the hypothesis that sphingoid bases are produced in cells in response to external stimuli. Using a high-performance liquid chromatography system, the pattern and the amounts of free sphingoid bases in various cell types (i.e., NIH-3T3, A431, NG108-15) were determined. The predominant sphingoid base in these mammalian cells was identified as C-18 sphingosine, followed by C-18 sphinganine (dihydrosphingosine). In all cells examined, the levels of endogenous sphingoid bases can be rapidly elevated by replacing cell-conditioned medium with Hepes-buffered saline or with fresh medium, causing a dramatic increase (up to 9.5-fold) in sphingosine levels within 60 min; sphinganine levels were raised to a lesser extent (up to 4.5-fold). Addition of ammonium ions inhibited the generation of sphingoid bases. These results suggest that the machinery for metabolizing sphingoid bases can be stimulated rapidly, although the exact nature of the stimulus remains obscure. Nevertheless, the ability to control sphingosine formation in cells by changing medium conditions provides a powerful tool for investigations of the physiological roles of endogenous sphingosine.
Assuntos
Esfingosina/análogos & derivados , Esfingosina/metabolismo , Células 3T3 , Animais , Carcinoma de Células Escamosas , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Meios de Cultura , Meios de Cultivo Condicionados , Humanos , Cinética , Camundongos , Esfingosina/isolamento & purificação , Células Tumorais CultivadasRESUMO
Choline deficiency is associated with triacylglycerol accumulation in the liver, and is the only nutritional state known to trigger hepatic cancer spontaneously. In two different experiments, rats were pair-fed for 6 weeks with control (0.2% choline), or choline-deficient (CD) (0.002% choline) diets. Hepatic choline and phosphocholine declined in CD animals to 54% and 16% of control levels, respectively. In control livers, 1,2-sn-diacylglycerol (1,2-sn-DAG) concentration was (in nmol/g wet wt) 144 (+/- 25; mean +/- SE); while in CD livers it was 792 (+/- 140) in the first experiment. In the second experiment the values were 375 (+/- 26) and 1147 (+/- 74), respectively. 1,2-sn-DAG, a precursor of triacylglycerol, is an endogenous activator of protein kinase C (PKC). PKC is the presumed site of action of the tumor-promoting phorbol esters. We suggest that the 1,2-sn-DAG accumulating in CD liver could bind PKC, altering its activity, and thus contribute to the carcinogenic effect of CD diets.
Assuntos
Deficiência de Colina/metabolismo , Diglicerídeos/metabolismo , Glicerídeos/metabolismo , Neoplasias Hepáticas/etiologia , Fígado/metabolismo , Proteína Quinase C/metabolismo , Animais , Carcinógenos/metabolismo , Colina/metabolismo , Ativação Enzimática , Neoplasias Hepáticas/metabolismo , Masculino , Fosforilcolina/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Modulation of mRNA expression of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) by the glucocorticoid dexamethasone and by retinoic acid was examined in two neuronal cell lines: basal forebrain-derived SN56 and pheochromocytoma PC12. Dexamethasone up-regulated ChAT and VAChT in SN56 cells, while it had inhibitory effects on these genes in PC12 cells. Retinoic acid stimulated the cholinergic markers in both cell types, but in SN56 cells its effect was partially additive with that of dexamethasone, whereas it was much smaller and abrogated by dexamethasone in PC12 cells. Acetylcholine content correlated with these mRNA changes. The presence of a glucocorticoid response element consensus sequence in the VAChT/ChAT gene locus suggests direct transcriptional regulation by glucocorticoids.
Assuntos
Acetilcolina , Proteínas de Transporte/genética , Colina O-Acetiltransferase/genética , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana Transportadoras , Tretinoína/farmacologia , Proteínas de Transporte Vesicular , Acetilcolina/metabolismo , Animais , Northern Blotting , Linhagem Celular , Glucocorticoides/farmacologia , Camundongos , Células PC12 , RNA Mensageiro/metabolismo , Ratos , Proteínas Vesiculares de Transporte de AcetilcolinaRESUMO
The function of a particular neuronal population is in part determined by its neurotransmitter phenotype. We have found that a neuronal-derived septal cell line (SN56), known for its cholinergic properties, also synthesizes and releases luteinizing hormone-releasing hormone. In addition, these cells express the messenger RNAs encoding estrogen and progesterone receptors. The activation of these receptors by their respective ligands cooperatively modulates the depolarization-induced release of luteinizing hormone-releasing hormone in these cells. We have also found that a number of septal neurons in postnatal (1-week-old) mice are immunoreactive to both choline acetyltransferase and luteinizing hormone-releasing hormone. These results indicate that both neurotransmitters, acetylcholine and luteinizing hormone-releasing hormone, may co-exist in septal neurons of the CNS and that they could be modulated by gonadal hormones, and suggest that luteinizing hormone-releasing hormone could be involved in some of the actions of sex steroids on cholinergic neurotransmission.
Assuntos
Colina O-Acetiltransferase/metabolismo , Hormônios Esteroides Gonadais/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Prosencéfalo/metabolismo , Animais , Animais Recém-Nascidos/metabolismo , Linhagem Celular , Eletrofisiologia , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Hormônio Liberador de Gonadotropina/genética , Imuno-Histoquímica , Camundongos , Neurônios/metabolismo , Prosencéfalo/citologia , Prosencéfalo/fisiologia , RNA Mensageiro/metabolismo , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: In cholinergic neurons, the hydrolysis of phosphatidylcholine (PC) by a phospholipase D (PLD)-type enzyme generates some of the precursor choline used for the synthesis of the neurotransmitter acetylcholine (ACh). We sought to determine the molecular identity of the relevant PLD using murine basal forebrain cholinergic SN56 cells in which the expression and activity of the two PLD isoforms, PLD1 and PLD2, were experimentally modified. ACh levels were examined in cells incubated in a choline-free medium, to ensure that their ACh was synthesized entirely from intracellular choline. RESULTS: PLD2, but not PLD1, mRNA and protein were detected in these cells and endogenous PLD activity and ACh synthesis were stimulated by phorbol 12-myristate 13-acetate (PMA). Introduction of a PLD2 antisense oligonucleotide into the cells reduced PLD2 mRNA and protein expression by approximately 30%. The PLD2 antisense oligomer similarly reduced basal- and PMA-stimulated PLD activity and ACh levels. Overexpression of mouse PLD2 by transient transfection increased basal- (by 74%) and PMA-stimulated (by 3.2-fold) PLD activity. Moreover, PLD2 transfection increased ACh levels by 26% in the absence of PMA and by 2.1-fold in the presence of PMA. Overexpression of human PLD1 by transient transfection increased PLD activity by 4.6-fold and ACh synthesis by 2.3-fold in the presence of PMA as compared to controls. CONCLUSIONS: These data identify PLD2 as the endogenous enzyme that hydrolyzes PC to generate choline for ACh synthesis in cholinergic cells, and indicate that in a model system choline generated by PLD1 may also be used for this purpose.
Assuntos
Acetilcolina/biossíntese , Colina/biossíntese , Fosfolipase D/metabolismo , Acetato de Tetradecanoilforbol/análogos & derivados , Animais , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Líquido Intracelular/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Dados de Sequência Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosfolipase D/genética , RNA Mensageiro/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , TransfecçãoRESUMO
The selective vulnerability of certain cholinergic neurons in Alzheimer's disease could reflect a unique response of these neurons to a neurotoxic factor. Alternatively the etiologic factor causing the disease could affect the brain generally, and the selective death of the cholinergic neurons could occur because they have a biochemical property that makes them least able to withstand this factor. One such property might be their tendency to utilize choline-phospholipids both as a membrane constituent and as a source of free choline for acetylcholine synthesis: perhaps when choline levels in the brain's extracellular fluid are too low to sustain acetylcholine release, these neurons break down their choline-phospholipids more rapidly than they can synthesize them, thus changing membrane structure and, ultimately, neuronal viability.
RESUMO
The mouse neuroblastoma x rat glioma hybrid cell line, NG108-15, does not synthesize serotonin from tryptophan, although the cells take up tryptophan and serotonin in a saturable manner from serum-supplemented incubation medium. Since serum commonly used to supplement the growth medium contains serotonin, it is concluded that appreciable levels of serotonin found in NG108-15 cells are attributable to uptake of serotonin from the serum-supplemented medium.
RESUMO
To test the hypothesis that brain cell membranes degenerate in Alzheimer's disease (AD), we measured the levels of phospholipids, their water-soluble metabolites, and glycerophosphocholine (GPC) cholinephosphodiesterase activity in postmortem brain tissue from patients with AD and age-matched controls. We found significantly higher levels of the phospholipid catabolite GPC in AD brain. In contrast, choline and ethanolamine levels were significantly lower in AD, and phospholipid levels were slightly decreased. Furthermore, in AD the activity of the GPC-degrading enzyme GPC cholinephosphodiesterase was unaltered. Our results indicate that membrane phospholipid catabolism is increased in AD brain. Inasmuch as the tissue levels of initial phospholipid precursors were decreased, we suggest that phospholipid turnover is elevated in this neurodegenerative disease.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Glicerilfosforilcolina/metabolismo , Fosfatidiletanolaminas/metabolismo , Doença de Alzheimer/enzimologia , Humanos , Diester Fosfórico Hidrolases/metabolismoRESUMO
Choline supplementation during the second half of the gestational period in rats permanently improves visuospatial memory. Choline availability during this period also alters the turnover of choline and acetylcholine in the hippocampus in 3-4 week-old animals in a complex pattern consistent with the notion that cholinergic neurotransmission is enhanced by prenatal choline supplementation.
Assuntos
Acetilcolina/metabolismo , Colina/metabolismo , Impressão Genômica , Hipocampo/metabolismo , Prenhez/metabolismo , Transmissão Sináptica/fisiologia , Animais , Feminino , Idade Gestacional , Gravidez , Ratos , Ratos Sprague-DawleyAssuntos
Encéfalo/embriologia , Encéfalo/fisiologia , Colina/administração & dosagem , Colina/metabolismo , Acetilcolina/metabolismo , Envelhecimento , Animais , Apoptose , Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Divisão Celular , Deficiência de Colina/fisiopatologia , Cognição , Dieta , Feminino , Hipocampo/metabolismo , Humanos , Potenciação de Longa Duração , Troca Materno-Fetal , Memória , Política Nutricional , Gravidez , RatosRESUMO
We have investigated the rates of acetylcholine (ACh) synthesis and release in LA-N-2 cells in order to characterize them as a potential model of cholinergic neurons. When grown in a serum-containing medium the cells extend few neurites. In the absence of serum most cells develop processes. ACh content of the cells (determined by a radioenzymatic assay) varies with extracellular choline concentration in a saturable fashion, reaching a maximum of approximately 25 nmol/mg protein. Radiolabeled choline is taken up by the cell and converted to ACh or phosphocholine, as determined by purification from cell extracts by HPLC, in a saturable manner which is described by a single rectangular hyperbola. Hemicholinium-3 (100 microM) inhibits this uptake. The cells release ACh spontaneously and this release is enhanced upon depolarization with potassium or veratridine (the latter effect is blocked by tetrodotoxin). The data demonstrate that LA-N-2 cells exhibit some properties similar to cholinergic neurons and may therefore be useful for studies of ACh synthesis and release.
Assuntos
Acetilcolina/metabolismo , Fibras Colinérgicas/metabolismo , Neuroblastoma , Células Tumorais Cultivadas/metabolismo , Linhagem Celular , Colina/farmacocinética , Fibras Colinérgicas/efeitos dos fármacos , Hemicolínio 3/farmacologia , Humanos , Potássio/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Veratridina/farmacologiaRESUMO
This study examined the possibility that membrane phospholipids might be a source of choline used for acetylcholine (ACh) synthesis. Slices of rat striatum or cerebellum were superfused with a choline-free or choline-containing (10, 20 or 40 microM) physiological solution with eserine, for alternating 20 min periods of rest or electrical stimulation. Superfusion media were assayed for choline and ACh, and slice samples taken before and after stimulation were assayed for choline, ACh, various phospholipids, protein and DNA. The striatal slices were able to sustain the stimulation-induced release of ACh, releasing a total of about 3 times their initial ACh contents during the 8 periods of stimulation and rest. During these 8 cycles, 885 pmol/micrograms DNA free choline was released from the slices into the medium, an amount about 45-fold higher than the initial or final free choline levels in the slices. Although repeated stimulation of the striatal slices failed to affect tissue levels of free choline or of ACh, this treatment did cause significant, dose-related (i.e., number of stimulation periods) stoichiometric decreases in tissue levels of phosphatidylcholine (PC) and of the other major phospholipids; tissue protein levels also declined significantly. Addition of exogenous choline to the superfusion medium produced dose-related increases in resting and evoked ACh release. The choline also fully protected the striatal slices from phospholipid depletion for as many as 6 stimulation periods. Cerebellar slices liberated large amounts of free choline into the medium but did not release measurable quantities of ACh; their phospholipid and protein levels did not decline with electrical stimulation. These data show that membrane phospholipids constitute a reservoir of free choline that can be used for ACh synthesis. When free choline is in short supply, ACh synthesis and release are sustained at the expense of this reservoir. The consequent reduction in membrane PC apparently is associated with a depletion of cellular membrane. The use of free choline by cholinergic neurons for two purposes, the syntheses of both ACh and membrane phospholipids, may thus impart vulnerability to them in situations where the supply of free choline is less than that needed for acetylation.
Assuntos
Acetilcolina/metabolismo , Colina/farmacologia , Corpo Estriado/metabolismo , Lipídeos de Membrana/metabolismo , Fosfolipídeos/metabolismo , Animais , Cerebelo/metabolismo , Cerebelo/fisiologia , Corpo Estriado/fisiologia , Estimulação Elétrica , Técnicas In Vitro , Masculino , Ratos , Ratos EndogâmicosRESUMO
This study determined whether the effect of all-trans-retinoic acid (t-RA) on markers of cholinergic differentiation in a murine septal cell line, SN56.B5.G4, differed depending upon the cell's proliferative status. To develop a model of non-proliferating cells, aphidicolin, a DNA alpha-polymerase inhibitor, was used. Cessation of proliferation by aphidicolin increased intracellular choline and acetylcholine (ACh) levels in the absence of change to choline acetyltransferase (ChAT) activity and mRNA and vesicular ACh transporter (VAChT) mRNA. Importantly, the response to t-RA differed depending upon proliferative status. Consistent with previous reports, t-RA increased ChAT and VAChT mRNA, ChAT activity and intracellular ACh levels in proliferating SN56 cells with no effect on intracellular choline levels. When cells were treated with t-RA while undergoing proliferative arrest, an additive effect of combined treatment was observed on ACh levels; nevertheless, this was only accompanied by an increase in choline levels, VAChT and ChAT mRNAs, but not ChAT activity. Indeed, aphidicolin treatment completely suppressed the t-RA-induced increase in ChAT activity observed in proliferating cells. To explore the response to t-RA in post-mitotic cells, a sequential treatment of aphidicolin and t-RA was employed. t-RA treatment was ineffective in increasing ACh and choline levels, over and above that observed with the aphidicolin treatment alone. Comparable to the combined treatment, sequential treatment lead to an increase in ChAT mRNA without any increase in ChAT activity. In conclusion, both the magnitude and the mechanism(s) of action whereby t-RA enhances the cholinergic phenotype of SN56 cells is dependent upon the cell's proliferative status.
Assuntos
Acetilcolina/metabolismo , Colina O-Acetiltransferase/metabolismo , Colina/metabolismo , Proteínas de Membrana Transportadoras , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Tretinoína/farmacologia , Proteínas de Transporte Vesicular , Animais , Afidicolina/farmacologia , Proteínas de Transporte/genética , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Colina O-Acetiltransferase/genética , DNA Polimerase III/antagonistas & inibidores , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Camundongos , RNA Mensageiro/metabolismo , Células Tumorais Cultivadas , Proteínas Vesiculares de Transporte de AcetilcolinaRESUMO
Choline molecules are needed for the synthesis of acetylcholine and phospholipids in the mammalian brain. An enzymatic activity capable of forming lecithin (phosphatidylcholine) from the step-by-step methylation of phosphatidylethanolamine is identified in the bovine brain. This enzyme(s), phosphatidylethanolamine-N-methyltransferase (EC 2.1.1.17), is localized in the synaptosomal fraction of bovine caudate nucleus, uses S-adenosylmethionine as the methyl donor (apparent Km = 20 micrometers), and has a Vmax of 50--60 pmol/mg protein X h (i.e. about 1% of that found in rat liver). The brain may be able to meet some of its choline requirements by de novo synthesis.
Assuntos
Núcleo Caudado/enzimologia , Fosfatidilcolinas/biossíntese , Fosfatidiletanolaminas/metabolismo , Animais , Bovinos , Cinética , Metilação , Metiltransferases/metabolismo , Fosfatidiletanolamina N-Metiltransferase , Sinaptossomos/enzimologiaRESUMO
Concentrations of glycerophosphocholine and of glycerophosphoethanolamine, the metabolites of two major membrane phospholipid classes, phosphatidylcholine and phosphatidylethanolamine respectively, were determined post-mortem in cortical areas 20 and 40 and in cerebellum and caudate nucleus of brains obtained at autopsy from patients with Alzheimer's disease, Down's syndrome and age-matched control subjects. Glycerophosphocholine concentrations in all of the brain regions examined were higher by 67-150% in Alzheimer's disease than in control brains and 81-104% higher in Alzheimer's disease than in Down's syndrome. Glycerophosphoethanolamine concentrations were 21-52% higher in Alzheimer's disease than in controls, and 27-92% higher in Alzheimer's disease than Down's syndrome. Levels of glycerophosphocholine and of glycerophosphoethanolamine did not differ significantly between Down's syndrome and control brains. These data indicate that abnormal phospholipid metabolism in brain is characteristic of Alzheimer's disease but not Down's syndrome and suggest that this abnormality may be a central pathophysiological feature of Alzheimer's disease because levels of glycerophosphocholine and of glycerophosphoethanolamine are elevated in brain regions with and without manifestations of histopathology.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Síndrome de Down/metabolismo , Glicerilfosforilcolina/metabolismo , Fosfatidiletanolaminas/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Degeneração Neural/fisiologiaRESUMO
Phospholipase D (PLD) activity and PLD1 mRNA levels were determined in rat brain at ages ranging from embryonic day (E) 19 to postnatal day (P) 49. Basal, oleate-, and phosphatidylinositol-4, 5-bisphosphate-stimulated PLD activity increased between E19 and P24 by approximately 3-fold and remained unaltered thereafter. A similar developmental pattern of mRNA levels of PLD1 isoform was found by Northern blotting. The development of PLD correlates with synaptogenesis and myelination suggesting that the enzyme might have an important function in these processes.