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Implication des cellules gliales dans la modulation de l’activité synaptique à la jonction neuromusculaire sénescenteMoustaine, Ayman 10 1900 (has links)
No description available.
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Neuromodulation des réseaux neuronaux : contrôle sérotoninergique de la balance excitation-inhibition dans le cortex visuel de rat.Moreau, Alexandre 11 December 2009 (has links) (PDF)
Le traitement de l'information sensorielle par le cortex cérébral requiert l'activation harmonieuse de micro-circuits neuronaux excitateurs et inhibiteurs interconnectés, ciblant les neurones pyramidaux de couche 5. Ces derniers élaborent les signaux de sortie corticaux et reçoivent un ratio de 20% d'excitation (E) et 80% d'inhibition (I). La dérégulation de cette balance E-I ou du système sérotoninergique conduit à des neuropathologies telles la dépression et la schizophrénie mais les interrelations entre la sérotonine et la balance E-I sont inconnues. Nous avons montré que la 5-HT endogène module la balance E-I en fonction du type de récepteur 5-HT recruté (1A, 2A, 3, 4, 7) et de sa localisation spécifique dans la colonne corticale. Ces données électrophysiologiques constituent la première évidence pour une action modulatrice fine de la sérotonine corticale sur la balance E-I et révèle la ségrégation fonctionnelle des récepteurs 5-HT dans les réseaux de neurones sensoriels.
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Emergence de circuits neuromimétiques orientés sous l'effet de l'épissage associé à la plasticité synaptique à modulation temporelle relative (STDP)Iglesias, Javier 22 August 2005 (has links) (PDF)
L'élagage massif des synapses après une croissance excessive est une phase normale de la maturation du cerveau des mammifères. L'élagage commence peu avant la naissance et est complété avant l'âge de la maturité sexuelle. Les facteurs déclenchants capables d'induire l'élagage des synapses pourraient être liés à des processus dynamiques qui dépendent de la temporalité relative des potentiels d'actions. La plasticité synaptique à modulation temporelle relative STDP correspond à un changement de la force synaptique basé sur l'ordre des décharges pré- et post-synaptiques. La relation entre l'efficacité synaptique et l'élagage des synapses suggère que les synapses les plus faibles pourraient être modifiées et retirées au moyen d'une règle "d'apprentissage" faisant intervenir une compétition. Cette règle de plasticité pourrait produire le renforcement des connections parmi les neurones qui appartiennent à une assemblée de cellules caractérisée par des motifs de décharge récurrents. A l'inverse, les connections non activées de façon récurrente pourraient voir leur efficacité diminuée et être finalement éliminées. Le but principal de notre travail est de déterminer dans quelles conditions de telles assemblées pourraient émerger d'un réseau d'unités integrate-and-fire connectées aléatoirement à la surface d'une grille bidimensionnelle recevant à la fois du bruit et des entrées organisées dans les dimensions temporelle et spatiale. L'originalité de notre étude tient dans la taille relativement grande du réseau, 10'000 unités, dans la durée des simulations, 1 million d'unités de temps, et dans l'utilisation d'une règle STDP originale compatible avec une implémentation matérielle.
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Induktion und Spezifikation serotonerger Neurone des ventralen Rhombencephalon der Maus / Induction and specification of serotonergic neurons from mouse ventral rostral hindbrainOsterberg, Nadja 12 January 2009 (has links)
No description available.
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ETUDE DU MODE D'ACTION NEUROTOXIQUE D'UN REPULSIF, LE DEET UTILISE SEUL ET EN ASSOCIATION AVEC UN INSECTICIDE SUR L'ACETYLCHOLINESTERASE DES DUM NEURONES D'UN INSECTE LA BLATTE PERIPLANETA AMERICANAMohamed, Aly Ahmed Abd-Ella 31 March 2011 (has links) (PDF)
Le DEET (N, N-diéthyl-m-toluamide), est connu comme le répulsif le plus utilisé au monde. Bien qu'il soit efficace contre un large groupe d'arthropodes, son mode d'action exact et sa cible moléculaire ne sont pas encore connus précisément. Grâce à l'utilisation des techniques d'électrophysiologie (patch-clamp et oil-gap), d'imagerie calcique et biochimique, nous avons étudié le mode d'action du DEET sur des cellules neurosécrétrices identifiées, les DUM neurones de la blatte Periplaneta americana. Le DEET, à forte concentration, inhibe l'activité de l'acétylcholinestérase (AChE) au niveau du DUM neurone. A faible concentration, il induit une augmentation de la concentration en calcium intracellulaire via l'activation des récepteurs cholinergiques de type muscariniques (mAChRs). Dans un deuxième temps, les interactions synergiques entre le DEET et le propoxur, un carbamate connu pour inhiber l'AChE, ont été étudiées. Les résultats ont révélé que les mAChRs, correspondent bien à une nouvelle cible potentielle pour le DEET et qu'ils sont impliqués dans l'effet synergique. Le DEET, à faible et à forte concentration, agit sur des sites allostériques positifs et négatifs des mAChRs respectivement. L'action du DEET sur le site allostérique positif des mAChRs est responsable de l'effet synergique via une augmentation de la concentration en calcium intracellulaire qui potentialise l'effet anti-AChE du propoxur. L'utilisation d'outils pharmacologiques sélectifs a permis l'identification de la voie de signalisation intracellulaire (PLC, PI-PLC, CaMKinase II, récepteurs IP3) impliquée dans l'effet synergique du propoxur. Les résultats présentés dans ce mémoire vont contribuer au développement de nouvelles stratégies basées sur l'utilisation de combinaisons d'insecticides de familles chimiques différentes afin de réduire les doses des traitements tout en augmentant l'efficacité.
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The monoamine oxidase inhibition properties of caffeine analogues containing saturated C–8 substituents / Paul GroblerGrobler, Paul Johan January 2010 (has links)
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized
pathologically by a marked loss of dopaminergic nigrostriatal neurons and clinically by disabling
movement disorders. PD can be treated by inhibiting monoamine oxidase (MAO), specifically
MAO–B, since this is a major enzyme involved in the catabolism of dopamine in the substantia
nigra of the brain. Inhibition of MAO–B may conserve the dopamine supply in the brain and may
therefore provide symptomatic relief for PD patients.
Selegiline is an irreversible MAO–B inhibitor and is currently used for the treatment of PD.
Irreversible inhibitors inactivate enzymes by forming stable covalent complexes. The process is
not readily reversed either by removing the remainder of the free inhibitor or by increasing the
substrate concentration. Even dilution or dialysis does not dissociate the enzyme inhibitor
complex and restore enzyme activity. From a safety point of view it may therefore be more
desirable to develop reversible inhibitors of MAO–B. In this study, caffeine was used as lead
compound to design, synthesize and evaluate new reversible inhibitors of MAO–B. This study is
based on the finding that C–8 substituted caffeine analogues are potent MAO inhibitors.
For example, (E)–8–(3–chlorostyryl)caffeine (CSC) is an exceptionally potent competitive inhibitor
of MAO–B with an enzyme–inhibitor dissociation constant (Ki value) of 128 nM. In this study
caffeine was similarly conjugated at C–8 to various side–chains. The effect that these chosen
side–chains had on the MAO–B inhibition activity of C–8 substituted caffeine analogues will then
be evaluated. The caffeine analogues were also evaluated as human MAO–A inhibitors. For the
purpose of this study, saturated C–8 side chains were selected with the goal of discovering new
C–8 side chains that enhance the MAO–A and ?B inhibition potency of caffeine. As mentioned
above, the styryl side chain is one example of a side chain that enhances the MAO–B inhibition
potency of caffeine. Should a side chain with promising MAO inhibition activity be identified in this study, the inhibition potency will be further optimized in a future study by the addition of a
variety of substituents to the C–8 side chain ring. For example, halogen substitution of (E)–8–
styrylcaffeine enhances the MAO–B inhibition potency by up to 10 fold. The saturated side
chains selected for the present study included the phenylethyl (1), phenylpropyl (2), phenylbutyl
(3) and phenylpentyl (4) functional groups. Also included are the cyclohexylethyl (8), 3–oxo–3–
phenylpropyl (5), 4–oxo–4–phenylbutyl (6) moieties. A test compound containing an unsaturated
linker between C–8 of caffeine and the side chain ring, the phenylpropenyl analogue 7, was also
included. This study is therefore an exploratory study to discover new C–8 moieties that are
favorable for MAO– inhibition. All the target compounds were synthesized by reacting 1,3–dimethyl–5,6–diaminouracil with an
appropriate carboxylic acid in the presence of a carbodiimide dehydrating agent. Following ring
closure and methylation at C–7, the target inhibitors were obtained. Inhibition potencies were
determined using recombinant human MAO–A and MAO–B as enzyme sources. The inhibitor
potencies were expressed as IC50 values. The most potent MAO–B inhibitor was 8–(5–
phenylpentyl)caffeine (4) with an IC50 value of 0.656 ?M. In contrast, all the other test inhibitors
were moderately potent MAO–B inhibitors. In fact the next best MAO–B inhibitor, 8–(4–
phenylbutyl)caffeine (3) was approximately 5 fold less potent than 4 with an IC50 value of 3.25
?M. Since the 5–phenylpentyl moiety is the longest side chain evaluated in this study, this
finding demonstrates that longer C–8 side chains are more favorable for MAO–B inhibition. Interestingly, compound 5 containing a cyclohexylethyl side chain (IC50 = 6.59 ?M) was
approximately 4 fold more potent than the analogue containing the phenylethyl linker (1) (IC50 =
26.0 ?M). This suggests that a cyclohexyl ring in the C–8 side chain of caffeine may be more
optimal for MAO–B inhibition and should be considered in future studies. The caffeine analogues
containing the oxophenylalkyl side chains (5 and 6) were weak MAO–B inhibitors with IC50
values of 187 ?M and 46.9 ?M, respectively. This suggests that the presence of a carbonyl
group in the C–8 side chain is not favorable for the MAO–B inhibition potency of caffeine. The
unsaturated phenylpropenyl analogue 7 was also found to be a relatively weak MAO–B inhibitor
with an IC50 value of 33.1 ?M.
In contrast to the results obtained with MAO–B, the test caffeine analogues were all weak MAOA
inhibitors. With the exception of compound 5, all of the analogues evaluated were selective
inhibitors of MAO–B. The most potent MAO–B inhibitor, 8–(5–phenylpentyl)caffeine (4) was the
most selective inhibitor, 48 fold more potent towards MAO–B than MAO–A.
This study also shows that two selected analogues (5 and 3) bind reversibly to MAO–A and ?B,
respectively, and that the mode of MAO–A and –B inhibition is competitive for these
representative compounds. / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.
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The monoamine oxidase inhibition properties of caffeine analogues containing saturated C–8 substituents / Paul GroblerGrobler, Paul Johan January 2010 (has links)
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized
pathologically by a marked loss of dopaminergic nigrostriatal neurons and clinically by disabling
movement disorders. PD can be treated by inhibiting monoamine oxidase (MAO), specifically
MAO–B, since this is a major enzyme involved in the catabolism of dopamine in the substantia
nigra of the brain. Inhibition of MAO–B may conserve the dopamine supply in the brain and may
therefore provide symptomatic relief for PD patients.
Selegiline is an irreversible MAO–B inhibitor and is currently used for the treatment of PD.
Irreversible inhibitors inactivate enzymes by forming stable covalent complexes. The process is
not readily reversed either by removing the remainder of the free inhibitor or by increasing the
substrate concentration. Even dilution or dialysis does not dissociate the enzyme inhibitor
complex and restore enzyme activity. From a safety point of view it may therefore be more
desirable to develop reversible inhibitors of MAO–B. In this study, caffeine was used as lead
compound to design, synthesize and evaluate new reversible inhibitors of MAO–B. This study is
based on the finding that C–8 substituted caffeine analogues are potent MAO inhibitors.
For example, (E)–8–(3–chlorostyryl)caffeine (CSC) is an exceptionally potent competitive inhibitor
of MAO–B with an enzyme–inhibitor dissociation constant (Ki value) of 128 nM. In this study
caffeine was similarly conjugated at C–8 to various side–chains. The effect that these chosen
side–chains had on the MAO–B inhibition activity of C–8 substituted caffeine analogues will then
be evaluated. The caffeine analogues were also evaluated as human MAO–A inhibitors. For the
purpose of this study, saturated C–8 side chains were selected with the goal of discovering new
C–8 side chains that enhance the MAO–A and ?B inhibition potency of caffeine. As mentioned
above, the styryl side chain is one example of a side chain that enhances the MAO–B inhibition
potency of caffeine. Should a side chain with promising MAO inhibition activity be identified in this study, the inhibition potency will be further optimized in a future study by the addition of a
variety of substituents to the C–8 side chain ring. For example, halogen substitution of (E)–8–
styrylcaffeine enhances the MAO–B inhibition potency by up to 10 fold. The saturated side
chains selected for the present study included the phenylethyl (1), phenylpropyl (2), phenylbutyl
(3) and phenylpentyl (4) functional groups. Also included are the cyclohexylethyl (8), 3–oxo–3–
phenylpropyl (5), 4–oxo–4–phenylbutyl (6) moieties. A test compound containing an unsaturated
linker between C–8 of caffeine and the side chain ring, the phenylpropenyl analogue 7, was also
included. This study is therefore an exploratory study to discover new C–8 moieties that are
favorable for MAO– inhibition. All the target compounds were synthesized by reacting 1,3–dimethyl–5,6–diaminouracil with an
appropriate carboxylic acid in the presence of a carbodiimide dehydrating agent. Following ring
closure and methylation at C–7, the target inhibitors were obtained. Inhibition potencies were
determined using recombinant human MAO–A and MAO–B as enzyme sources. The inhibitor
potencies were expressed as IC50 values. The most potent MAO–B inhibitor was 8–(5–
phenylpentyl)caffeine (4) with an IC50 value of 0.656 ?M. In contrast, all the other test inhibitors
were moderately potent MAO–B inhibitors. In fact the next best MAO–B inhibitor, 8–(4–
phenylbutyl)caffeine (3) was approximately 5 fold less potent than 4 with an IC50 value of 3.25
?M. Since the 5–phenylpentyl moiety is the longest side chain evaluated in this study, this
finding demonstrates that longer C–8 side chains are more favorable for MAO–B inhibition. Interestingly, compound 5 containing a cyclohexylethyl side chain (IC50 = 6.59 ?M) was
approximately 4 fold more potent than the analogue containing the phenylethyl linker (1) (IC50 =
26.0 ?M). This suggests that a cyclohexyl ring in the C–8 side chain of caffeine may be more
optimal for MAO–B inhibition and should be considered in future studies. The caffeine analogues
containing the oxophenylalkyl side chains (5 and 6) were weak MAO–B inhibitors with IC50
values of 187 ?M and 46.9 ?M, respectively. This suggests that the presence of a carbonyl
group in the C–8 side chain is not favorable for the MAO–B inhibition potency of caffeine. The
unsaturated phenylpropenyl analogue 7 was also found to be a relatively weak MAO–B inhibitor
with an IC50 value of 33.1 ?M.
In contrast to the results obtained with MAO–B, the test caffeine analogues were all weak MAOA
inhibitors. With the exception of compound 5, all of the analogues evaluated were selective
inhibitors of MAO–B. The most potent MAO–B inhibitor, 8–(5–phenylpentyl)caffeine (4) was the
most selective inhibitor, 48 fold more potent towards MAO–B than MAO–A.
This study also shows that two selected analogues (5 and 3) bind reversibly to MAO–A and ?B,
respectively, and that the mode of MAO–A and –B inhibition is competitive for these
representative compounds. / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.
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ALS-En livsförändring i vardagen : -En litteraturöversikt / ALS-A life change in everyday life : -A litterature reviewCarina, Engström, Fogelström, Ludvig, Julia, Granbom January 2018 (has links)
Syfte: Att beskriva närståendes upplevelser av att leva med en person med ALS. Metod: En litteraturöversikt med kvalitativ metod och en induktiv ansats. Resultat: Sjukdomen ALS är ovanlig och de som drabbas av den är i stort behov av omvårdnad. Närstående till en anhörig som har fått diagnosen ALS, upplever att vårdpersonalen har kunskapsbrist angående sjukdomen och vårdandet. De upplever bristande information om sjukdomens förlopp. Egentiden tas ifrån dem, sådant som förr togs förgivet läggs istället åt sidan, då all fokus ligger på den anhöriges omvårdnad. Slutsats: Närstående väljer ofta att vårda den anhöriga i hemmet, trots det snabba sjukdomsförloppet. Vårdandet av den anhöriga leder till känslomässiga påfrestningar hos de närstående, både psykiska och fysiska. / Purpose: To describe next of kin experiences of living with person with ALS. Method: A literature review with qualitative method and an inductive approach. Result: The disease ALS is unusual and those who suffer from it are in great need of nursing. The next of kin those who has been diagnosed with ALS, find that healthcare professionals have a lack of knowledge regarding the disease and care. They experience insufficient information about the course of the disease. The true time is taken away from them, as was previously taking for granted, instead being put aside, as all focus is on the patient's nursing. Conclusion: Next of kin often choose to care for their relatives in spite of the progress of the ilness. The care of the relatives leads to emotional stresses of the related, both mental and physical.
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Fabrication de microstructures pour le recrutement de protéines synaptiques par polymérisation à deux photonsGagnon, Maxime 12 1900 (has links)
No description available.
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Recherche des oscillations de neutrinos par apparition du τ avec désintégration muonique du vτ dans l’expérience OPERATran, Ngoc Tiem 18 October 2010 (has links)
La physique des oscillations de neutrinos occupe une place majeure dans les études s’intéressant à cetteparticule. Le mécanisme des oscillations, basé sur un changement d’état de saveur d’un neutrino durant sapropagation, permet d’élucider les déficits observés de neutrinos solaires et atmosphériques et apporte des indicationsintéressantes de physique au delà du Modèle Standard par l'étude des angles de mélanges et du schéma de masse desneutrinos.OPERA est un détecteur hybride combinant à la fois latechnique d'une détection électronique en temps réel et la technique de la chambre à brouillard à émulsion ou ECC(EmulsionCloud Chamber). Le détecteur ECC est un détecteur massif (cible) composé de 150000 briques dontchacune est constituée de feuilles de plombs, utilisées comme cible, alternées avec des émulsions nucléaires dont laprécision de reconstruction des traces est de l'ordre du micron. Le détecteur comprend également deux spectromètresavec des plaques de fer magnétisé de 5 cm d'épaisseur alternées avec les détecteurs RPC (Resistive Plate Chamber)associés à six ensembles de drift tubes (PT) pour la mesure de la charge et de l'impulsion du muon, et un plan de vetoservant à la rejection des particules extérieures à la cible. / The physics of neutrino oscillations plays a major role in studies concerned with cetteparticule. The mechanism of oscillations, based on a change of state of a neutrino flavor during sapropagation, elucidates the deficits observed solar and atmospheric neutrinos and provides indicationsintéressantes of physics beyond the Standard Model by studying the angles mixtures and mass desneutrinos.OPERA scheme is a hybrid sensor combining both latechnique an electronic real-time detection technology and the cloud chamber emulsion or ECC (EmulsionCloud chamber). The ECC is a solid detector detector (target) consisting of bricks dontchacune 150000 consists of sheets of lead, used as a target, with alternate nuclear emulsion whose traces laprécision reconstruction is of the order of one micron. The detector also includes two spectromètresavec magnetized iron plates 5 cm alternating with RPC (Resistive Plate Chamber) detectors associated with six sets of drift tubes (PT) to measure the charge and momentum of the muon thickness and plan vetoservant the rejection of foreign particles to the target.
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