Maria Angelica De Souza Silva

Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (10)31.7 Total impact

  • Armin Zlomuzica · Dorothea Dere · Sonja Binder · Maria Angelica De Souza Silva · Joseph P Huston · Ekrem Dere
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    ABSTRACT: Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · May 2015 · Neuropharmacology
  • Susanne Nikolaus · Maria Angelica de Souza Silva · Hubertus Hautzel · Hans-Wilhelm Muller
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    ABSTRACT: Despite the knowledge, which has been accumulated on the central and peripheral actions of the neurokinin (NK) substance P (SP) over the last 80 years, it is only beginning to receive the attention of nuclear medicine physicians and scientists. Recently, two foci of interest have emerged: firstly, the performance of in vivo imaging studies of cerebral NK1 receptor binding with non-peptidergic NK1 receptor radioligands, and, secondly, radionuclide therapy with radiolabelled SP analogues targeting NK1 receptor binding sites. The present paper gives an overview on the utilization of nonpeptidergic and peptidergic NK1 receptor radioligands in diagnostics and therapy.
    No preview · Article · Jul 2013
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    ABSTRACT: Disturbances of dopaminergic neurotransmission may be caused by changes in concentrations of synaptic dopamine (DA) and/or availabilities of pre- and post-synaptic transporter and receptor binding sites. We present a series of experiments which focus on the regulatory mechanisms of the dopamin(DA)ergic synapse in the rat striatum. In these studies, DA transporter (DAT) and/or D(2) receptor binding were assessed with either small animal single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after pharmacological challenge with haloperidol, L-DOPA and methylphenidate, and after nigrostriatal 6-hydroxydopamine lesion. Investigations of DAT binding were performed with [(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([(123)I]FP-CIT). D(2) receptor bindingd was assessed with either [(123)I](S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([(123)I]IBZM) or [(18)F]1[3-(4'fluorobenzoyl)propyl]-4-(2-keto-3-methyl-1-benzimidazolinyl)piperidine ([(18)F]FMB). Findings demonstrate that in vivo investigations of transporter and/or receptor binding are feasible with small animal SPECT and PET. Therefore, tracers that are radiolabeled with isotopes of comparatively long half-lives such as (123)I may be employed. Our approach to quantify DAT and/or D(2) receptor binding at baseline and after pharmacological interventions inducing DAT blockade, D(2) receptor blockade, and increases or decreases of endogenous DA concentrations holds promise for the in vivo assessment of synaptic function. This pertains to animal models of diseases associated with pre- or postsynaptic DAergic deficiencies such as Parkinson's disease, Huntington's disease, attention-deficit/hyperactivity disorder, schizophrenia or drug abuse.
    No preview · Article · Nov 2011 · Reviews in the neurosciences
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    ABSTRACT: Excitation of the mesocorticolimbic pathway, originating from dopaminergic neurons in the ventral tegmental area (VTA), may be important for the development of exaggerated fear responding. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. The functional role of the dopaminergic pathway connecting the VTA to the basolateral amygdala (BLA) in fear and anxiety has received little attention. In vivo microdialysis was performed to measure dopamine levels in the BLA of Wistar rats that received the dopamine D(2) agonist quinpirole (1 μg/0.2 μl) into the VTA and were subjected to a fear conditioning test using a light as the conditioned stimulus (CS). The effects of intra-BLA injections of the D(1) antagonist SCH 23390 (1 and 2 μg/0.2 μl) and D(2) antagonist sulpiride (1 and 2 μg/0.2 μl) on fear-potentiated startle (FPS) to a light-CS were also assessed. Locomotor performance was evaluated by use of open-field and rotarod tests. Freezing and increased dopamine levels in the BLA in response to the CS were both inhibited by intra-VTA quinpirole. Whereas intra-BLA SCH 23390 did not affect FPS, intra-BLA sulpiride (2 μg) inhibited FPS. Sulpiride's ability to decrease FPS cannot be attributed to nonspecific effects because this drug did not affect motor performance. These findings indicate that the dopamine D(2) receptor pathway connecting the ventral tegmental area and the basolateral amygdala modulates fear and anxiety and may be a novel pharmacological target for the treatment of anxiety.
    No preview · Article · Oct 2010 · Neurobiology of Learning and Memory
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    ABSTRACT: Recently, it has been shown that human unrestricted somatic stem cells (USSCs) from umbilical cord blood represent pluripotent, neonatal, nonhematopoietic stem cells with the potential to differentiate into the neural lineage. However, molecular and functional characterization of the neural phenotype and evaluation of the degree of maturity of the resulting cells are still lacking. In this study, we addressed the question of neuronal differentiation and maturation induced by a defined composition of growth and differentiation factors (XXL medium). We demonstrated the expression of different neuronal markers and their enrichment in USSC cultures during XXL medium incubation. Furthermore, we showed enrichment of USSCs expressing tyrosine hydroxylase (TH), an enzyme specific for dopaminergic neurons and other catecholamine-producing neurons, accompanied by induction of Nurr1, a factor regulating dopaminergic neurogenesis. The functionality of USSCs has been analyzed by patch-clamp recordings and high-performance liquid chromatography (HPLC). Voltage-gated sodium-channels could be identified in laminin-predifferentiated USSCs. In addition, HPLC analysis revealed synthesis and release of the neurotransmitter dopamine by USSC-derived cells, thus correlating well with the detection of TH transcripts and protein. This study provides novel insight into the potential of unrestricted somatic stem cells from human umbilical cord blood to acquire a neuronal phenotype and function.
    No preview · Article · May 2008 · Stem Cells and Development
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    ABSTRACT: Dopamine plays an important role in learning and memory processes. A deficit of this neurotransmitter as it is apparent in Alzheimer's disease (AD) may contribute to cognitive decline, a major symptom of AD patients. The aim of this study was to elucidate whether or not stimulation of the dopaminergic system leads to an improvement of cognitive function and reduction of non-cognitive behavioral alterations in a murine model of AD. Transgenic and wild type male mice of the TgCRND8 line were treated either with the dopamine precursor levodopa or vehicle and tested in two learning tasks, the object-recognition task and the Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was analyzed. In both memory tasks wild type mice performed significantly better than transgenics. However, transgenics treated with levodopa showed a significant object recognition memory and improved acquisition of spatial memory in the Barnes maze compared to vehicle treated transgenics. Concerning spontaneous behavior transgenic mice performed much more stereotypies than wild types. However, there was a trend for reduced stereotypies in the levodopa group in the time the drug was active. Neurochemical analysis revealed elevated levels of dopamine in the neostriata and frontal cortices and reduced levels in the hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and stereotypies may be due to changes in the dopaminergic system as they could be ameliorated by levodopa treatment, that might also have a therapeutic significance for AD.
    No preview · Article · Jan 2008 · Neurobiology of aging
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    ABSTRACT: Consistent evidence has shown that dopamine release in the prefrontal cortex is increased by electrical stimulation of the inferior colliculus (IC) as unconditioned stimulus. Recent reports have also demonstrated that inactivation of the basolateral nucleus of the amygdala (BLA) with muscimol enhances the behavioural consequences of the aversive stimulation of the IC and reduces the dopamine release in the prefrontal cortex. Moreover, neurotoxic lesions of the BLA enhance whereas those of the central nucleus of the amygdala (CeA) reduce the aversiveness of the electrical stimulation of the IC. Based on these findings the present study examined the effects of the electrical stimulation of the IC on the extracellular levels of serotonin and dopamine in the BLA and CeA. To this end, rats implanted with a stimulation electrode in the IC also bore a microdialysis probe in the BLA or CeA for determination of the release of dopamine and serotonin. IC electrical stimulation at the freezing and escape thresholds increased the levels of serotonin ( approximately 70%) and dopamine ( approximately 60%) in the BLA related to the basal values. Similarly, the metabolites DOPAC and 5-HIAA increased in a parallel fashion in BLA. No significant changes could be detected in these biogenic amines and metabolites in CeA following IC aversive stimulation. These findings point to a differential role of serotonergic and dopaminergic mechanisms of the BLA and CeA in the setting up of adaptive responses to fear states generated at the inferior colliculus level.
    No preview · Article · Mar 2005 · European Journal of Neuroscience
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    ABSTRACT: We reported previously that the glycosaminoglycan heparin (HP) has the facility to improve learning in adult rodents when administered into the nucleus basalis of the ventral pallidum. Here we gauged the effects of chronic intraventricular infusion of HP (20 ng per day over 28 days) in 26-month-old rats in terms of Morris water maze performance, habituation to a novel open field, retention of a step-through inhibitory avoidance task and changes in forebrain acetylcholine (ACh) levels. Control groups included vehicle-infused old and adult (3-month-old) rats. The chronic infusion of HP did not significantly influence the performance of the old animals in any of the learning and memory tasks employed. HP only slightly facilitated the retention of the inhibitory avoidance task and the rate of habituation in the open-field paradigm. In the water maze, the glycosaminoglycan did not counteract the navigation deficits observed for aged controls and even impaired performance during the initial place-learning trials. After behavioural testing, tissue levels of ACh were determined in frontal cortex, ventral striatum, neostriatum and hippocampus without detecting any obvious neurochemical differences between groups. The current results, together with our previous work, indicate that HP differentially affects learning and memory parameters in adult and aged rats. Thus, whereas the glycosaminoglycan proved effective in facilitating mnemonic functions in normal adult animals, no such a clear-cut beneficial effect was observed in behaviourally impaired old rats.
    No preview · Article · Jan 2004 · Behavioural Brain Research
  • Marcus L Brandão · Ana Cristina Troncoso · Maria Angélica de Souza Silva · Joseph P Huston
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    ABSTRACT: The medial hypothalamus, amygdala, and dorsal periaqueductal gray constitute the main neural substrates for the integration of aversive states in the brain. More recently, some regions of the mesencephalon, such as the superior and inferior colliculi have also been proposed as part of this system. In fact, fear-like behaviors often result when these sites are electrically or chemically stimulated. Both the behavioral and autonomic consequences of electrical stimulation of the mesencephalic tectum have been shown to be attenuated by minor tranquilizers, probably through enhancement of gamma-aminobutyric acid (GABA)-mediated neurotransmission, which exerts a tonic inhibitory control on the neural circuits responsible for the so-called defense behavior repertoire. Besides GABA, also 5-hydroxy tryptamine serotonin (5-HT), opioids, neuropeptides, histaminergic and excitatory amino acids have all been implicated in the regulation of anxiety-related behaviors induced by stimulation of midbrain tectum. Efforts have been made to characterize how these neurotransmitters interact with each other in the organization of these reactions to aversive stimulation. In this review, we summarize the evidence linking the brain's defense response systems to the concept of fear-anxiety. Furthermore, a case is made for the consideration of the relevance of this body of data to the search for the physiological underpinnings of depression and its consequences.
    No preview · Article · Mar 2003 · European Journal of Pharmacology
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    ABSTRACT: In vivo microdialysis was used to assess the effects of unilateral substance P (SP) injection into the nucleus basalis magnocellularis on extracellular levels of acetylcholine (ACh) in the frontal cortex, either in freely moving or urethane-anesthetized rats. The results show that the neurochemical effects of SP are critically dependent on the choice of the experimental preparation: In the freely-moving rat, the injection procedure led to behavioral and concurrent bilateral cholinergic activation in the frontal cortex. This cholinergic activation was ipsilaterally reduced by intrabasalis injection of SP (1 ng), indicating that the peptide exerted an inhibitory influence on the neurochemical effect exerted by handling, intracranial needle insertion, and vehicle injection. In the anesthetized preparation, SP had a biphasic dose-dependent action on cortical ACh: a short-lasting ipsilateral increase immediately after injection (especially with 1 ng), and a delayed bilateral increase after more than 2 h (10, 100 ng). The procedure of inserting the injection needle moderately increased cortical ACh levels. Methodologically, these data are discussed with respect to the importance of using anesthetized vs. freely moving rats and the effects of intraparenchymal injections.
    No preview · Article · Jan 2001 · Synapse