Fundamental studies towards the fabrication of electroactive monolithic stationary phases in microfluidic channels

The long term goal of this project is to develop a monolithic stationary phase which utilises an electroactive polymer combining the advantages of EMLC, monolithic technology and microfluidic separation, thus creating an electroactive monolithic microchip (EMμ). In this thesis, fundamental studies towards the fabrication of EMμ are presented, i.e. integration of an electrochemical cell into a microfluidic chip, colloidal crystallization in microfluidic channels and PANI growth through a colloidal crystal template. Polyaniline was selected as the electroactive material for the fabrication of the monolithic stationary phase as its use for EMLC had already been demonstrated. Colloidal crystals have been used to microstructure materials and the inverse opal structure comprises pore sizes of the order of what was needed for EMμ; therefore electropolymerization of aniline through a polystyrene colloidal crystal template strategy was chosen. Two alternative chip designs, CD1 and CD2, were investigated for this thesis. Their applicability for EMμ was assessed in terms of their flow velocity profile using computational fluid dynamic, colloidal crystallization feasibility and electrochemical behavior using ferricyanide electrochemistry. The integration of a fully operational three-electrode electrochemical cell within a microfluidic channel and its use for polyaniline electropolymerization was demonstrated, and self-assembly of the sacrificial polystyrene template in these channels was shown. Polyaniline microstructure morphology exhibited a dependence on the surfactant concentration present in the polystyrene suspension. Finally, electrochemical switching of conducting polymer within microfluidic channels was assessed by studying polypyrrole switching by atomic force microscopy (AFM). Pore swelling and contraction was observed on application of a potential, demonstrating that the monolith properties could be dynamically controlled. It was found that volume increase in the polymer could be responsible for a deformation of flow through pores due to physical confinement of the polymer

In vivo PET quantification of the dopamine transporter in rat brain with [¹⁸F]LBT-999.

INTRODUCTION: We examined whether [(18)F]LBT-999 ((E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4'-tolyl)nortropane) is an efficient positron emission tomography (PET) tracer for the quantification of the dopamine transporter (DAT) in the healthy rat brain. METHODS: PET studies were performed using several experimental designs, i.e. test-retest, co-injection with different doses of unlabelled LBT, displacement with GBR12909 and pre-injection of amphetamine. RESULTS: The uptake of [(18)F]LBT-999 confirmed its specific binding to the DAT. The non-displaceable uptake (BP(ND)) in the striatum, between 5.37 and 4.39, was highly reproducible and reliable, and was decreased by 90% by acute injection of GBR12909. In the substantia nigra/ventral tegmental area (SN/VTA), the variability was higher and the reliability was lower. Pre-injection of amphetamine induced decrease of [(18)F]LBT-999 BP(ND) of 50% in the striatum. CONCLUSIONS: [(18)F]LBT-999 allows the quantification of the DAT in living rat brain with high reproducibility, sensitivity and specificity. It could be used to quantify the DAT in rodent models, thereby allowing to study neurodegenerative and neuropsychiatric diseases

Electroactive monolith μchips based on nanostructured polyaniline

The extensive application of monolithic columns for HPLC is severely hindered by a lack of column-to-column reproducibility. EMμ(Electroactive Monolithic μChip) is a new concept that solves the significant reproducibility problems, as well as allowing miniaturization and improving overall efficiency through electrochemically controlled dynamic separations. This novel μchip has a micro-structured monolith fabricated from intelligent, electroactive polymer. By application of a specific potential, conducting polymers such as polyaniline (PANI) can be reproducibly grown and readily fine-tuned in terms of porosity, hydrophobicity an d ionic capacity. This unique chip provides for an Electroac tive Monolithic μchip capable of multi-dimensional chromatographic separations. The monolith microstructuring (provided by templating) wi ll provide reproducibility and improve efficiency by decre asing the A-term of the Van Deemter equation. Furthermore, the use of these intelligen t materials will enable gradient control and redox reaction s to be exploited during separations of large biomolecules

EMµ: the next generation of separation science.

The extensive application of monolithic columns for HPLC is severely hindered by a lack of column-to-column reproducibility. EMμ (Electroactive Monolithic mChip) is a new concept that solves the significant reproducibility problems, as well as allowing miniaturization and improving overall efficiency through electrochemically controlled dynamic separations. This novel μchip has a micro-structured monolith fabricated from intelligent, electroactive polymer. By application of a specific potential, conducting polymers such as polyaniline (PANI) can be reproducibly grown and readily fine-tuned in terms of porosity, hydrophobicity and ionic capacity. This unique chip provides for an Electroactive Monolithic μchip capable of multi-dimensional chromatographic separations. Additionally, EMμ can exploit on-chip electrodes permitting incorporation of contactless conductivity detection (C4D). The monolith microstructuring (provided by templating) will provide reproducibility and improve efficiency by decreasing the A term of the Van Deemter equation. Furthermore, the use of these intelligent materials will enable gradient control and redox reactions to be exploited during separations of larges biomolecules

Synthesis and Characterization of Advanced Carbon-Based Nanowires – Study of Composites Actuation Capabilities Containing These Nanowires as Fillers

International audienc

Impulsive and compulsive behaviors can be induced by opposite GABAergic dysfunctions inside the primate ventral pallidum

Introduction: The ventral pallidum (VP) is central in the limbic Basal Ganglia circuit, controlling both appetitive (approach) and aversive (avoidance) motivated behaviors. Nevertheless, VP involvement in pathological aspects remains unclear, especially in the behavioral expression of different motivational dysfunctions. This study aimed to investigate how the VP contributes to the expression of abnormal behaviors via opposite GABAergic dysfunctions.Methods: Opposite GABAergic dysfunctions were induced by injecting muscimol (a GABAA agonist) and bicuculline (a GABAA antagonist) into monkeys. We determined the effects of both substances on self-initiated behaviors in lab-chair and in free-moving home-cage contexts in six monkeys, and in two animals performing an approach-avoidance task in appetitive and aversive contexts.Results: While the self-initiated behaviors induced by bicuculline injections in VP were characterized by compulsive behaviors such as repetitive grooming and self-biting, muscimol injections induced impulsive behaviors including limb movements in a lab-chair context and exploration behaviors in a free-moving context. More specific behavioral effects were observed in the approach-avoidance task. The muscimol injections induced premature responses and erroneous screen touches, which characterize impulsive and attention disorders, while the bicuculline injections into the VP increased passive avoidance (non-initiated action) and task-escape in an aversive context, suggesting an anxiety disorder.Conclusions: These results show that activating or blocking GABAergic transmission in the VP impairs motivated behaviors. Furthermore, the behavioral expressions produced by these opposite disturbances show that the VP could be involved in anxiety-driven compulsive disorders, such as OCD, as well as in impulsive disorders motivated by attention deficits or reward-seeking, as seen in ADHD or impulse control disorders

Maternal Exposure to Nitrogen Dioxide during Pregnancy and Offspring Birth Weight: Comparison of Two Exposure Models

International audienceThe two exposure models tended to give consistent results in terms of association with birth weight, despite the moderate concordance between exposure estimates

Étude des effets de l'administration chronique de substances psychoactives durant la gestation sur la maturation des systèmes monoaminergiques centraux chez le rat

Le but de ce travail a été d'étudier, chez le rat, la maturation des systèmes dopaminergiques et sérotoninergiques en conditions physiologiques, puis suite à une exposition prénatale au 3,4-méthylènedioxyméthamphétamine (MDMA ou ecstasy) et au méthylphénidate (MPH ou ritaline). Des paramètres neurochimiques et comportementaux ont été étudiés de la vie embryonnaire à l'âge adulte. Nous avons montré qu'une exposition prénatale au MDMA ou au MPH avait des conséquences transitoires et à long-terme sur le plan neurochimique et comportemental. Ces altérations concernent le fonctionnement des systèmes dopaminergiques et sérotoninergiques et semblent impliquer plus particulièrement les systèmes de récompense. Ces modèles animaux permettent de mieux comprendre les mécanismes d'action du MDMA et du MPH sur le cerveau en développement et peuvent constituer un outil de choix pour l'étude des mécanismes physiopathologiques impliqués dans les maladies neurodéveloppementales.In this work, we explored dopaminergic and serotonergic systems maturation under physiological conditions and after a prenatal exposure to 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) and methylphenidate (MPH or ritaline) in a rat model. Neurochemical and behavioral parameters were studied from embryonic life to adult ages. We demonstrated that a prenatal exposure to MDMA or MPH induce transient and long-term alterations of dopaminergic and serotonergic systems including neurochemichal and behavioral perturbations related to rewarding systems. These results raise the possibility that prenatal MDMA or MPH exposure in rat could be an interesting model to study developmental disturbances underlying neurodevelopmental disorders.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Traitement de l'insomnie (hypnotiques et thérapies comportementales)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF