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Chinese Journal of Preventive Medicine ; (12): 793-800, 2023.
Article in Chinese | WPRIM | ID: wpr-985474


Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.

Humans , Choline/metabolism , Phosphatidylcholines/metabolism , Central Nervous System/metabolism
Chinese Journal of Biotechnology ; (12): 45-59, 2023.
Article in Chinese | WPRIM | ID: wpr-970358


There are a variety of post-transcriptional modifications in mRNA, which regulate the stability, splicing, translation, transport and other processes of mRNA, followed by affecting cell development, body immunity, learning and cognition and other important physiological functions. m6A modification is one of the most abundant post-transcriptional modifications widely existing in mRNA, regulating the metabolic activities of RNA and affecting gene expression. m6A modified homeostasis is critical for the development and maintenance of the nervous system. In recent years, m6A modification has been found in neurodegenerative diseases, mental diseases and brain tumors. This review summarizes the role of m6A methylation modification in the development, function and related diseases of the central nervous system in recent years, providing potential clinical therapeutic targets for neurological diseases.

Methylation , Central Nervous System/metabolism , RNA, Messenger/metabolism , RNA
Journal of Zhejiang University. Medical sciences ; (6): 738-749, 2023.
Article in English | WPRIM | ID: wpr-971085


Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.

Humans , Fibroblast Growth Factors , Phosphatidylinositol 3-Kinases/metabolism , Central Nervous System/metabolism , Signal Transduction/physiology , Alzheimer Disease
Neuroscience Bulletin ; (6): 519-530, 2023.
Article in English | WPRIM | ID: wpr-971575


Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Animals , Neuroglia/metabolism , Central Nervous System/metabolism , Astrocytes/metabolism , Oligodendroglia/metabolism , Cerebral Small Vessel Diseases/metabolism , Antigens/metabolism , Mammals/metabolism
Journal of Zhejiang University. Medical sciences ; (6): 651-658, 2021.
Article in English | WPRIM | ID: wpr-922255


The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3‑containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3‑containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3‑containing atypical NMDARs and the physiological and pathological relevance.

Central Nervous System/metabolism , Protein Subunits/metabolism , Receptors, N-Methyl-D-Aspartate , Synapses
Arq. neuropsiquiatr ; 74(9): 737-744, Sept. 2016. graf
Article in English | LILACS | ID: lil-796045


ABSTRACT Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.

RESUMO A fisiologia celular está prejudicada antes da agregação proteica podendo ser mais importante para a neurodegeneração do que as próprias inclusões. Assim, o objetivo deste estudo é caracterizar um modelo animal para analisar os mecanismos e efeitos da agregação proteica. Ratos Lewis com 10 meses de idade foram expostos a rotenona (1 ou 2 mg/kg/dia), administrada subcutaneamente, utilizando minibombas osmóticas. Os níveis de peptídeo beta-amiloide, TAU hiperfosforilada, alfa-sinucleína e proteínas carboniladas (indicativo de estresse oxidativo) foram avaliados por imunohistoquímica e western blot no hipocampo, substância negra e locus coeruleus. Foi demonstrado que 2 mg/kg/dia de rotenona promoveu aumento do peptídeo beta-amiloide, hiperfosforilação da TAU e alfa-sinucleína. Já 1 mg/kg/dia de rotenona não alterou os níveis dessas proteína nessas regiões. As proteínas carboniladas não se alteraram. Foi demonstrado que ratos Lewis idosos expostos a baixas doses de rotenona são modelo de estudo dos processos celulares antes da agregação proteica, enquanto 2 mg/kg/dia de rotenona permite estudos sobre os efeitos da agregação proteica.

Animals , Male , Rotenone/administration & dosage , Central Nervous System/drug effects , Central Nervous System/pathology , Disease Models, Animal , Protein Aggregation, Pathological/chemically induced , Protein Aggregation, Pathological/pathology , Rats, Inbred Lew , Substantia Nigra/drug effects , Immunohistochemistry , Central Nervous System/metabolism , Blotting, Western , Reproducibility of Results , Amyloid beta-Peptides/drug effects , Amyloid beta-Peptides/metabolism , Oxidative Stress , alpha-Synuclein/drug effects , alpha-Synuclein/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 36(3): 251-258, Jul-Sep/2014. graf
Article in English | LILACS | ID: lil-718447


Sepsis and the multiorgan dysfunction syndrome are among the most common reasons for admission to an intensive care unit, and are a leading cause of death. During sepsis, the central nervous system (CNS) is one of the first organs affected, and this is clinically manifested as sepsis-associated encephalopathy (SAE). It is postulated that the common final pathway that leads to SAE symptoms is the deregulation of neurotransmitters, mainly acetylcholine. Thus, it is supposed that inflammation can affect neurotransmitters, which is associated with SAE development. In this review, we will cover the current evidence (or lack thereof) for the mechanisms by which systemic inflammation interferes with the metabolism of major CNS neurotransmitters, trying to explain how systemic inflammation drives the brain crazy.

Humans , Brain/physiopathology , Encephalitis/physiopathology , Sepsis-Associated Encephalopathy/physiopathology , Sepsis/physiopathology , Amines/metabolism , Brain/metabolism , Central Nervous System/metabolism , Central Nervous System/physiopathology , Cytokines/metabolism , Encephalitis/metabolism , Sepsis-Associated Encephalopathy/metabolism , Sepsis/metabolism , gamma-Aminobutyric Acid/metabolism
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 36(2): 156-167, may. 13, 2014. graf
Article in English | LILACS | ID: lil-710208


Introduction: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. Methodology: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. Results: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. Conclusions: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects. .

Humans , Central Nervous System/physiopathology , Mental Disorders/physiopathology , Mitochondria/physiology , Mitochondrial Diseases/physiopathology , Apoptosis/physiology , Central Nervous System/metabolism , Energy Metabolism , Mental Disorders/etiology , Mental Disorders/metabolism , Mitochondria/drug effects , Mitochondrial Diseases/metabolism
São Paulo; s.n; s.n; out. 24, 2013. 133 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-836965


Diversos estudos relatam os efeitos da exposição à nicotina nos períodos pré e pós-natal, contudo, pouco se sabe a respeito dos efeitos da fumaça do cigarro na cascata de eventos que caracteriza o desenvolvimento do sistema nervoso central (SNC). Neste contexto, o objetivo deste trabalho foi esclarecer se a exposição à fumaça do cigarro no início do período pós-natal induz prejuízo ao desenvolvimento do SNC na infância, e as possíveis consequências na adolescência e na fase adulta. Camundongos BALB/c foram expostos a uma mistura de fumaça central e lateral do cigarro referência 3R4F (Universidade de Kentucky, EUA), desde o 3° dia de vida pós-natal (P) até P14 por duas horas diárias. Nossos resultados indicam que a exposição à fumaça do cigarro no início do período pós-natal induz prejuízo ao processo de aprendizado e memória e aumento na ansiedade em todas as idades avaliadas, além de induzir diminuição da atividade locomotora na infância e na adolescência. Ainda, observamos diminuição dos níveis de BDNF e das proteínas sinápticas sinapsina e sinaptofisina no hipocampo, cerebelo, córtex pré-frontal e estriado. A fumaça do cigarro também induz diminuição na porcentagem de fibras mielinizadas no nervo óptico e aumento da proteína básica de mielina (PBM) no cerebelo na infância, além de diminuição da PBM no telencéfalo e tronco encefálico na adolescência e no cerebelo na fase adulta. Nossos resultados sugerem que a exposição à fumaça do cigarro no início do período pós-natal causa prejuízo ao desenvolvimento do SNC, sendo que não há reversão dos efeitos observados no aprendizado e memória ou mesmo nos níveis de proteína pré-sináptica na adolescência e na fase adulta

Several studies show the effects of nicotine exposure during pre- and postnatal period. However, little is known about the effects of environmental tobacco smoke (ETS) in the cascade of events that characterizes the brain development. Thus, the aim of this study was to evaluate the effects of ETS in early brain development. BALB/c mice were exposed to a mixture of mainstream and sidestream of tobacco smoke of reference cigarettes 3R4F (University of Kentucky, EUA) from the 3rd (P3) to the 14th (P14) day of life, during 2h/day. Our results showed that ETS induced impairment in learning and memory and increased anxiety in all the ages evaluated. In addition, there was a decrease in locomotor activity during childhood and adolescence. ETS also induced impairment in synaptic transmission, by a decrease in synapsin, synaptophysin and BDNF in hippocampus, cerebellum and prefrontal cortex as compared to the control group. The percentage of myelinated fibers in the optic nerve in childhood and in myelin basic protein (MBP) in the telencephalon and brainstem were lower in adolescents mice exposed to ETS when compared to the control group. In cerebellum, there was an increase in MBP in infants and a decrease in adults compared to the control group. Taken all together, our results suggest that the exposure to ETS in the early postnatal period induces impairment to the brain development. It is noteworthy that the effects on learning and memory or even in the presynaptic protein levels were not reversed in adolescence and adulthood

Animals , Male , Mice , Tobacco Smoke Pollution/analysis , Central Nervous System/metabolism , Tobacco Products , Nicotiana , Toxicology , Toxicology/standards , Environmental Exposure
Mem. Inst. Oswaldo Cruz ; 108(6): 730-734, set. 2013. tab, graf
Article in English | LILACS | ID: lil-685488


Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies (Abs) represents conclusive evidence of a specific immune response in the central nervous system of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a confirmatory test for HTLV-1 infection. The aim of this study was to standardise the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1 proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative patients and two HTLV-1 patients without definite HAM/TSP. The presence of reactive bands of greater intensity in the CSF compared to serum (or bands in only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1 Abs; these Abs were not detected in the control patients. The most frequent intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal immune response against env (GD21 and rgp46-I) and gag (p24) proteins represents the most important humoral pattern in HAM/TSP. This response may be used as a diagnostic marker, considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis with HAM/TSP and the pathogenesis of this neurological disease.

Humans , Antibodies, Viral , Blotting, Western/standards , Central Nervous System/immunology , Human T-lymphotropic virus 1/immunology , Paraparesis, Tropical Spastic/immunology , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Central Nervous System/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Products, env/immunology , Gene Products, gag/immunology , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Paraparesis, Tropical Spastic/blood , Paraparesis, Tropical Spastic/cerebrospinal fluid , Sensitivity and Specificity
Article in Portuguese | LILACS | ID: lil-604944


Epidemiological studies indicate the health protective effect of fruits andvegetables. A significant part of this effect may be due to their contentof flavonoids. These bioactive compounds from vegetables in the diet of humans feature many biological properties. Such properties include the ones related to the Central Nervous System physiology. Currently, literature suggests that flavonoids can modulate many enzymes, including those with anti-inflammatory action, in reduction of atherosclerotic plaques, inhibition of platelet aggregation, vasodilation, exhibit hormonal activity (specifically isoflavones) and significant antioxidant activity. Studies indicate that the prevalence of mental illness in developed countries increased in correlation with the deterioration of the dietary pattern of these populations, as a result of Western Diet adoption. Flavonoids pass beyond the Blood-Brain Barrier through several channels, most of which are still under investigation, and reach almost all brain nuclei. These compounds are able to increase the antioxidant capacity of the brain and improve its blood perfusion, interact with neuronal genes and modulate the activity of certain neuronal receptors. The data reported in this review reinforce the recommendations for promoting the consumption of fruits and vegetables, which supply food flavonoids, in order to prevent and treat diseases affecting the Central Nervous System, as recommended bythe World Health Organization.

Los estudios epidemiológicos muestran el efecto protector de la salud del consumo de frutas y verduras, que puede ser en gran parte atribuidoa los flavonoides. Estos compuestos bioactivos provenientes de los vegetales de la dieta humana, presentan numerosas propiedades biológicas. Entre ellas se encuentran las actividades relacionadas con la fisiología del Sistema Nervioso Central. En la actualidad, la literatura sugiere que los flavonoides por mediode la modulación de numerosas enzimas, tienen acción en el sistema vascular, incluyendo acción antiinflamatoria, de reducción delas placas arterioscleróticas, inhibiciónde la agregación plaquetaria, promociónde vasodilatación, actividad hormonal (específicamente las isoflavonas) y significativa actividad antioxidante. Los estudios indican que la prevalencia de enfermedades mentales en los países desarrollados aumentó en correlación con la deterioración de los hábitos alimentarios de estas poblaciones, como resultado de la adopción de la dieta occidental. Los flavonoides penetran la barrera hematoen cefálica através de varios canales, la mayoría de los cuales están todavía bajo investigación, y alcanzan prácticamente todos los núcleos cerebrales. Estos compuestos son capaces de aumentar la capacidad antioxidante del cerebro, mejorar su perfusión sanguínea, interactuar con genes neuronales y modular la actividad de receptores neuronales. Los datos presentados en esta revisión refuerzan las recomendaciones depromoción del consumo de frutas y hortalizas, los principales proveedores de flavonoides de la dieta, de acuerdo con la OMS, a fin de preveniry tratar enfermedades que afectan el Sistema Nervioso Central.

Estudos epidemiológicos demonstram o efeito protetor à saúde do consumo de frutas e hortaliças; uma parcela significativa deste efeito pode ser atribuída aos flavonoides. Estes compostos bioativos, provenientes dos vegetais presentes na dieta dos seres humanos, exibem inúmeras propriedades biológicas. Dentre elas, destacam-se atividades ligadas à fisiologiado Sistema Nervoso Central. Atualmente, a literatura aponta que os flavonoides são capazes de modular numerosas enzimas, têm ação no sistema vascular, inclusive ação anti-inflamatória, redução de placas ateroscleróticas, inibição da agregação plaquetária, promoção da vasodilatação, ação hormonal (especificamente isoflavonas) e significante atividade antioxidante. Estudos apontam que a prevalência de doenças mentais aumentou nos países desenvolvidos em correlação com a deterioração do padrão alimentar destas populações, como resultado da adoção da Dieta Ocidental. Os flavonoidesultra passam a Barreira Hemato-Encefálica por diversas vias, a maioria das quais ainda em investigação, e atingem praticamente todos os núcleos cerebrais. Estes compostos são capazes de aumentar a capacidade antioxidante do cérebro, melhorar sua perfusão sanguínea, interagir com genes neuronais e modulara atividade de determinados receptores neuronais. Os dados relatados nesta revisão reforçam as recomendações de promoção do consumo de frutas e hortaliças, principais fornecedores de flavonoides na alimentação, em consonância com a OMS, como modo deprevenir e tratar doenças que acometem o Sistema Nervoso Central.

Flavonoids/analysis , Flavonoids/biosynthesis , Central Nervous System/enzymology , Central Nervous System/metabolism , Nervous System Diseases/prevention & control , Micronutrients/therapeutic use , Phytotherapeutic Drugs , Plants/chemistry
Rev. colomb. biotecnol ; 13(1): 42-51, jul. 2011. graf, ilus, tab
Article in Spanish | LILACS | ID: lil-600572


Los modelos experimentales en rata han sido de gran utilidad en las evaluaciones terapéuticas o de reemplazo de células en enfermedades neurodegenerativas. Se ha comprobado que las células de la médula ósea (CMO) de ratas pueden diferenciarse en células que no forman parte de sus linajes normales. Hay evidencias de estos procesos de trans-diferenciación, pero aún no se conocen los mecanismos moleculares que activan estos procesos. El propósito de nuestro trabajo fue estudiar el polimorfismo genético del ADN de los tipos celulares que conforman las CMO y las células del sistema nervioso central (SNC), estríatales y de la corteza de ratas mediante la técnica de RAPD. Las CMO, las células mononucleares (CMMO), las células estromales (CEMO) y las del SNC fueron obtenidas de ratas, y su ADN genómico fue purificado y amplificado mediante la técnica de RAPD, utilizando 15 cebadores al azar. Se construyó un dendograma de las bandas de amplificación generadas utilizando el método de UPGMA. Las células estudiadas según el análisis del RAPD quedaron en 2 grupos bien definidos, pudiéndose diferenciar las CEMO del resto de las células estudiadas. Los cebadores OPA-6, 7 y 12, mostraron el polimorfismo genético de los linajes de células estudiadas. Mediante la técnica de RAPD se demostró la variabilidad genética entre las CEMO y las CMMO, células estriadas y de corteza que mostraron una homogeneidad genética, proponiéndose marcadores específicos de RAPD para cada grupo de células. Este es el primer estudio del polimorfismo genético de las CMO y del SNC de ratas.

Experimental models have been of grate usefulness in the therapeutic or replacement cells in neurodegenerative diseases. It has been demonstrated that bone marrow cells (BMC), can be difefferentiated in cells that do not form part of their normal lineage. There is evidence of these trans-differentiation processes in these cells, but nevertheless, molecular mechanisms that activate these differentiation process still not known. The purpose of our work was to study the genetic polymorphism of those cellular types; that conform the rat bone marrow cells (BMC) as well as those of the central nervous system (CNS), striatum cells and cortex ones, trough RAPD technique. BM, mononuclear cells (BMMC), estromal cells (BMSC) and the CNS cells were obtained from rats and genomic ADN was purified and amplified through RAPD technique, using 15 random primers. A dendogram was constructed according to UPGMA method of the amplifying RAPD bands. Studied cells as- according to the RAPD analysis- were grouped into 2 well- defined groups, as CEMO coud be differentiated from the rest of studied cells. OPA-6, 7 and 12 primers showed the genetic polymorphism of the studied lineages cells. Also will be proposed specific RAPD genetic markers. Through RAPD technique permitted the genetic variability was demonstrated betwen BMEC and BMMC of striated cells and of cortex, which demonstratd a genetic homogeneity through RAPD technique so specific genetic markers of RAPD were thus propose for each group of cells. These constitute the first study on genetic polymorphism of BMC and CNS.

Bone Marrow/abnormalities , Bone Marrow/growth & development , Bone Marrow/immunology , Bone Marrow/ultrastructure , Polymorphism, Genetic/physiology , Polymorphism, Genetic/genetics , Random Amplified Polymorphic DNA Technique , Central Nervous System/abnormalities , Central Nervous System/injuries , Central Nervous System/metabolism , Central Nervous System/microbiology , Central Nervous System/ultrastructure
Indian J Biochem Biophys ; 2011 Apr; 48(2): 73-81
Article in English | IMSEAR | ID: sea-135303


Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. PPAR-alpha is involved in wound healing, stimulation of lipid and folic acid catabolism, inflammation control, inhibition of ureagenesis and peroxisome proliferation. The PPAR/ is involved wound healing, cell proliferation, embryo implantation, adipocyte differentiation, myelination alteration and apoptosis. The PPAR is involved in fat, lipid and calorie utilization, sugar control, inflammation control and macrophage (MQ) matutation. Homocysteine (Hcy) binds to nuclear peroxisome proliferator activated receptor. Increase in PPAR expression decreases the level of nitrotyrosine and increases endothelial nitric oxide concentration, decreases metalloproteinase activity and expression as well as elastinolysis and reverses Hcy-mediated vascular dysfunction. The PPAR initially recognized as a regulator of adipocyte development has become a potential therapeutic target for the treatment of diverse disorders. In addition, the activation of PPAR receptor ameliorates neurodegenerative disease. This review focuses on the recent knowledge of PPAR in neuroprotection and deals with the mechanism of neuroprotection of central nervous system disorder by PPAR.

Animals , Brain Ischemia/metabolism , Brain Ischemia/pathology , Brain Ischemia/therapy , Cell Death , Central Nervous System/cytology , Central Nervous System/metabolism , Central Nervous System/pathology , Cytoprotection , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/therapy , Neurons/cytology , Neurons/pathology , Neuroprotective Agents/metabolism , PPAR gamma/metabolism
Article in English | IMSEAR | ID: sea-135596


The role of apolipoprotein E (apo E) in lipid metabolism and cholesterol transport is well established. About 14 per cent of the variation in plasma cholesterol levels is attributed to polymorphisms in apo E gene (APOapo E). E consists of three common alleles, designated as ε2, ε3 and ε4 which code for E2, E3 and E4 proteins respectively resulting in three homozygous (E2/E2, E3/E3, E4/E4) and three heterozygous (E3/E2, E4/E2 and E4/E3) phenotypes. Different populations studied worldwide inherit variable frequencies of the E alleles and genotypes, with the most frequent allele being ε3.The ε4 allele has been consistently shown to be associated with Alzheimer’s disease, coronary heart disease and cerebrovascular disorders. In this review, we have discussed the role of apo E polymorphisms in cerebrovascular and coronary heart diseases. The status of apo E polymorphisms and their disease associations in Asian Indians besides, other populations has also been discussed. Further, studies elucidating the pathophysiology of apo E deficiency conducted in knock-out mice have been reviewed.

Alleles , Alzheimer Disease/genetics , Animals , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Central Nervous System/metabolism , Cerebrovascular Disorders/genetics , Cholesterol/metabolism , Coronary Disease/genetics , Humans , India , Lipids/blood , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Mice , Mice, Knockout , Polymorphism, Genetic/genetics
Rev. chil. nutr ; 35(supl.1): 250-260, nov. 2008. ilus
Article in Spanish | LILACS | ID: lil-523024


Alzheimer's disease (AD) is a major public health problem in many countries of the world; however the specific cause of this disease is still unknown. Currently, a bulk of evidence supports the hypothesis that beta-amiloidpeptide could be the cause of synaptic injuries and neuronal death observed at the initial stages of the disease. Patients with AD show lower levels of docosahexaenoic acid (DHA, C22:6; omega-3) in plasma and brain tissue, as compared with age-matched controls. In addition, epidemiological studies indicate that a high intake of DHA may have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that diets rich in DHA reduce synaptic injuries and cognitive defects induced by the beta-amyloid peptide. Although the molecular basis of these neuroprotective effects are still unknown, a number of mechanisms have been proposed to explain this protection, such as: regulation in the expression of potentially protective genes, activation of anti-inflammatory pathways, and modulation of the functional properties of neuronal membranes along with changes in their structural characteristics and physical-chemical properties. The present work reviews and discusses the molecular basis of the hypothesis on the protective role of DHA in the prevention of AD.

La enfermedad de Alzheimer (EA) constituye un importante problema de salud pública en muchos países del mundo, sin embargo la causa específica de esta enfermedad todavía es desconocida. Actualmente, numerosas evidencias apoyan la hipótesis que modificaciones del péptido beta-amiloide podrían ser la causa más próxima de las lesiones sinápticas y muerte neuronal que ocurren en las etapas iniciales de la enfermedad. Los pacientes con EA muestran niveles más bajos de ácido docosahexaenoico (DHA, C22: 6; omega-3) en plasma y tejido cerebral, en comparación con controles pareados por edad. Además, los estudios epidemiológicos indican que una alta ingesta de DHA podría tener propiedades protectoras contraías enfermedades neurodegenerativas. Estas observaciones se sustentan por estudios in vivo que demuestran que las dietas ricas en DHA, limitan las lesiones sinápticas y disminuyen los defectos cognitivos inducidos por el péptido beta-amiloide. Aunque las bases moleculares de estos efectos neuroprotectores aún siguen siendo desconocidas, se han propuesto varios mecanismos, tales como: la regulación de la expresión de genes potencialmente protectores, la activación de vías antiinflamatorias, la modulación de las propiedades funcionales de las membranas neuronales, junto con cambios en las características estructurales y físico-químicas de las mismas. Este trabajo revisa y discute el fundamento molecular de estas hipótesis sobre el rol del DHA en la protección de la EA.

Humans , Diet , Docosahexaenoic Acids , Alzheimer Disease/prevention & control , Docosahexaenoic Acids , Alzheimer Disease/metabolism , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/prevention & control , Inflammation , Oxidative Stress , Amyloid beta-Peptides/metabolism , Central Nervous System/metabolism
Biocell ; 32(1): 1-8, Apr. 2008. ilus
Article in English | LILACS | ID: lil-541117


Cellular and subcellular organization and distribution of actin filaments have been studied with various techniques. The use of fluorescence photo-oxidation combined with phalloidin conjugates with eosin has allowed the examination of the precise cellular and subcellular location of F-actin. Correlative fluorescence light microscopy and transmission electron microscopy studies of F-actin distribution are facilitated with this method for morphological and physiological studies. Because phalloidin-eosin is smaller than other markers, this method allows the analysis of the three-dimensional location of F-actin with high-resolution light microscopy, three-d serial sections reconstructions, and electron tomography. The combination of selective staining and three-dimensional reconstructions provide a valuable tool for revealing aspects of the synaptic morphology that are not available when conventional electron microscopy is used. By applying this selective staining technique and three-dimensional imaging, we uncovered the structural organization of actin in the postsynaptic densities in physiological and pathological conditions.

Humans , Animals , Actins/metabolism , Eosine Yellowish-(YS)/pharmacology , Eosine Yellowish-(YS)/metabolism , Photooxidation , Central Nervous System/metabolism , Central Nervous System/ultrastructure , Staining and Labeling/methods , Fluorescent Dyes/pharmacology , Phalloidine/pharmacology , Imaging, Three-Dimensional/methods , Models, Molecular , Actin Cytoskeleton/metabolism , Actin Cytoskeleton/ultrastructure , Microscopy, Fluorescence/methods , Oxidation-Reduction , Photons
Indian J Exp Biol ; 2008 Mar; 46(3): 185-90
Article in English | IMSEAR | ID: sea-60069


Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.

Animals , Anticonvulsants/pharmacology , Antidepressive Agents/pharmacology , Biogenic Monoamines/metabolism , Central Nervous System/metabolism , Dopamine/metabolism , Male , Motor Activity/drug effects , Norepinephrine/metabolism , Pentylenetetrazole/toxicity , Phytotherapy/methods , Plant Extracts/chemistry , Plant Leaves/chemistry , Rats , Rats, Sprague-Dawley , Seizures/chemically induced , Serotonin/metabolism , Spinacia oleracea/chemistry
RBCF, Rev. bras. ciênc. farm. (Impr.) ; 42(1): 17-27, jan.-mar. 2006. tab
Article in Portuguese | LILACS | ID: lil-431420


O efeito ergogênico da cafeína sobre a performance em exercícios físicos anaeróbios ainda não esta claro, da mesma forma que os mecanismos de ação envolvidos nesse tipo de esforço físico. As teorias que têm tentado explicar o efeito ergogênico da cafeína durante o exercício físico anaeróbio esta relacionada ao efeito da cafeína em alguma porção do sistema nervoso central (SNC), e a propagação dos sinais neurais entre o cérebro e a junção neuromuscular, e também ao efeito da cafeína sobre o músculo esquelético, facilitando a estimulação-contração do músculo esquelético. Alguns estudos têm indicado aumento da força muscular acompanhado de maior resistência à instalação do processo de fadiga muscular após a ingestão de cafeína. Sugere-se que isso ocorra muito mais pela ação direta da cafeína no SNC do que pela sua ação em nível periférico. Com relação aos exercícios máximos e supramáximos de curta duração, os estudos têm-se demonstrado controversos, embora a maior parte indique que a cafeína parece melhorar significativamente a performance em exercícios máximos de curta duração (<5 min), quando não precedidos por exercícios submáximos prolongados. Entretanto, esses resultados necessitam de confirmação, assim como de maior esclarecimento quanto aos mecanismos de ação da cafeína nesses tipos de esforços.

Caffeine/toxicity , Exercise , Muscle, Skeletal , Central Nervous System/metabolism , Muscle Fatigue