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Author: Christine Winter (113)


Feb
2018

Reduced activity of vagal efferents has long been implicated in schizophrenia and appears to be responsible for diminished parasympathetic activity and associated peripheral symptoms such as low heart rate variability and cardiovascular complications in affected individuals. In contrast, only little attention has been paid to the possibility that impaired afferent vagal signaling may be relevant for the disorder's pathophysiology as well. The present study explored this hypothesis using a model of subdiaphragmatic vagal deafferentation (SDA) in male rats.

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Jan
2018

Involuntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS.

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Jan
2018

There is ample evidence that obsessive-compulsive disorder (OCD) is based on reduced serotonergic function. Replicated bidirectional selection for thermoregulatory nest-building behavior in the laboratory house mouse (Mus musculus) resulted in compulsive-like, non-compulsive-like and randomly bred control mice that represent a non-induced animal model of OCD. The present study aimed at investigating the neurochemical patterns in specific brain regions of compulsive-like (HA) versus non-compulsive-like (LA) and normal (CA) mice.

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Dec
1969

Infection of poultry with low pathogenic avian influenza viruses (LPAIV) is often associated with mild respiratory symptoms but may also lead to loss in egg production in laying birds.susceptibility of the reproductive tract for LPAIV infection was reported for turkeys and chickens, but virus-interaction with epithelial cells of the oviduct and possible stimulation of the local antiviral immune responses have not been characterized. In this study, we wanted to investigate the suitability of magnum organ cultures (MOC) as anmodel to study virus-host interactions.

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Dec
1969

To investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naïve rats.
43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery.

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Dec
2016

The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene.

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Jul
2017

In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype.

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Dec
1969

Alcohol use disorder (AUD) is a severe chronic condition characterized by compulsive alcohol use, cravings and high relapse rates even after long periods of abstinence. It is suggested that alterations in neuronal network activity, especially in the reward pathway accompany or even mediate relapse behavior. Here we used a DSM-based rat model to map in a first set of experiments neurochemical alterations in the reward pathway during alcohol relapse.

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Dec
1969

Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy-refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease.

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Dec
1969

Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.

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May
2017

Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs.

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Oct
2015

Patients with post-traumatic stress disorder (PTSD) may fail to achieve adequate relief despite treatment with psychotherapy, pharmacotherapy, or complementary medicine treatments. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation procedure that can alter neuronal activity through administration of various pulse sequences and frequencies. TMS may theoretically have promise in correcting alterations observed in patients with PTSD.

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Sep
2015

To date, the effects of deep brain stimulation (DBS) on hippocampal neurogenesis have been mainly characterized in the context of memory. Acute stimulation (i.e.

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Aug
2015

A growing body of evidence sheds light on the neurodevelopmental nature of schizophrenia with symptoms typically emerging during late adolescence or young adulthood. We compared the pre-symptomatic adolescence period with the full symptomatic period of adulthood at the behavioral and neurobiological level in the poly I:C maternal immune stimulation (MIS) rat model of schizophrenia. We found that in MIS-rats impaired sensorimotor gating, as reflected in disrupted prepusle inhibition (PPI), emerged post-pubertally, with behavioral deficits being only recorded in adulthood but not during adolescence.

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Sep
2015

A significant portion of patients suffering from major depression remains refractory to available antidepressant treatment strategies. This highlights the need for a better understanding of the underlying neuropathology in order to develop rationale-based treatments. Here we aimed to further characterize neurobiological abnormalities of the Flinders Sensitive Line (FSL) rat model of depression.

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May
2015

Mesenchymal stem cells (MSC) are easily harvested, and possess anti-inflammatory and trophic properties. Furthermore, MSC promote neuroprotection and neurogenesis, which could greatly benefit neurodegenerative disorders, such as Parkinson's disease.
MSC were transplanted one week after 6-hydroxydopamine lesioning and effects were evaluated after 6 months.

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May
2015

In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for patients suffering from treatment-resistant depression (TRD). Several stimulation targets have successfully been tested in clinical settings, including the subgenual cingulum (Cg25) and the medial forebrain bundle (MFB). MFB-DBS has led to remarkable results, surpassing the effect of previous targets in terms of response latency and number of responders.

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Feb
2015

In Parkinson's disease (PD), neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) axis is affected as the result of the lack of dopaminergic innervations reaching the SVZ. This aberrant network has been related to the hyposmia of PD patients, which is an early diagnostic marker of the disease. Consequently, much interest arose in finding mechanisms to modulate the SVZ-OB axis.

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Feb
2015

Many viruses infect and replicate in their host via the intestinal tract, e.g. many picornaviruses, several coronaviruses and avian influenza viruses of waterfowl.

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Sep
2014

The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2(hum)), cortico-basal ganglia circuits are specifically affected.

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Dec
2014

Environmental factors have long been known to regulate brain plasticity. We investigated the potential influence of social experience on ocular dominance plasticity. Fully adult female or male mice were monocularly deprived for four days and kept a) either alone or in pairs of the same sex and b) either in a small cage or a large, featureless arena.

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Feb
2015

Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson's disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD.

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Jun
2014

The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which makes a complete control of the disease by vaccinations a challenging task. Reasons for differences in the tissue tropism and pathogenicity between IBV strains, e.

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May
2014

Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system.

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Jun
2014

Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to HMPV is incomplete and short-lived. We used gene-deletion viruses to evaluate the role of the attachment G and small hydrophobic SH glycoproteins on virus uptake by primary human monocyte-derived dendritic cells (MDDC) in vitro and on subsequent MDDC maturation and activation of autologous T cells.

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Jun
2014

[Bats, viruses and humans: coronaviruses on the rise?].

Berl Munch Tierarztl Wochenschr 2013 Nov-Dec;126(11-12):509-13
Christine Winter, Georg Herrler
The outbreak of the SARS coronavirus in 2002/2003 and the recent disease cases with a new human coronavirus (originally designated EMC-CoV, recently renamed MERS-CoV) have put the focus onto the virus family Coronaviridae. Both viruses appeared to have managed to jump over the species barrier from a bat reservoir to the human population. Bats are considered to serve as a natural reservoir for coronaviruses infecting mammals.

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May
2014

Adult neurogenesis in the hippocampus is impaired in schizophrenic patients and in an animal model of schizophrenia. Amongst a plethora of regulators, the immune system has been shown repeatedly to strongly modulate neurogenesis under physiological and pathological conditions. It is well accepted, that schizophrenic patients have an aberrant peripheral immune status, which is also reflected in the animal model.

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May
2014

One of the two core symptoms of major depression (MD), whether uni- or bipolar, is the inability to experience pleasure, suggested to be triggered by dysregulation within the brain reward system. In recent years, deep brain stimulation (DBS) has evolved as a potential tool to modulate pathological neural activity; stimulation of the subgenual cingulate (Cg25) has been shown to reduce depressive symptoms, including anhedonia. In rodents, the ventromedial prefrontal cortex (vmPFC) is likely to represent the correlate of Cg25 and accordingly, stimulation of vmPFC reduces anhedonia-like behavior in rats.

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Dec
2013

Serological screening and detection of genomic RNA indicates that members of the genus Henipavirus are present not only in Southeast Asia but also in African fruit bats. We demonstrate that the surface glycoproteins F and G of an African henipavirus (M74) induce syncytium formation in a kidney cell line derived from an African fruit bat, Hypsignathus monstrosus. Despite a less broad cell tropism, the M74 glycoproteins show functional similarities to glycoproteins of Nipah virus.

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Oct
2013

Despite there being a relatively large number of methods papers which detail specifically the development of stimulation devices, only a small number of reports involve the application of these devices in freely moving animals. To date multiple preclinical neural stimulators have been designed and described but have failed to make an impact on the methods employed by the majority of laboratories studying DBS. Thus, the overwhelming majority of DBS studies are still performed by tethering the subject to an external stimulator.

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Jul
2013

The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV) and the spike protein of infectious bronchitis virus (IBV).

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Aug
2013

The inflammation regulating transcription factor NFκB and the tumor-suppressing transcription factor p53 can act as functional antagonists. Chronic inflammation (NFκB activity) may contribute to the development of cancer through the inhibition of p53 function, while, conversely, p53 activity may dampen inflammation. Here we report that the E3 ubiquitin ligase MDM2, whose gene is transcriptionally activated by both NFκB and p53, can bind and inhibit the p65RelA subunit of NFκB.

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Jun
2013

Existing antipsychotic drugs are most effective in the treatment of the positive symptoms of schizophrenia. However, they are associated with considerable side effects and have relatively low efficacy. Diminished inhibitory control in the hippocampus has been suggested to lead to hyperactivation of the dopamine system thus underpinning the dopamine-dependent psychosis associated with schizophrenia.

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Mar
2013

Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry.

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Mar
2013

To effectively study the mechanisms by which deep brain stimulation (DBS) produces its therapeutic benefit and to evaluate new therapeutic indications, it is vital to administer DBS over an extended period of time in awake, freely behaving animals. To date multiple preclinical stimulators have been designed and described. However, these stimulators have failed to incorporate some of the design criteria necessary to provide a system analogous to those used clinically.

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Feb
2013

Human respiratory syncytial virus (RSV) is the leading viral cause of lower respiratory tract disease in infants and children worldwide. In previous work to develop point mutations in RSV with improved genetic stability, we observed that an attenuating mutation at amino acid position 1321 in the L polymerase protein was subject to deattenuation by a spontaneous second-site compensatory mutation at position 1313 (C. Luongo, C.

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Jul
2013

The development of more efficient treatment remains a major unmet need in the realm of schizophrenia disease. Using the maternal immune stimulation and the pubertal cannabinoid administration rat model of schizophrenia, the present study aimed at testing the hypothesis that deep brain stimulation (DBS) serves as a novel therapeutic technique for this disorder.
Adult offspring of dams, treated with the immune activating agent poly I:C (4 mg/kg, n = 50) or saline (n = 50), underwent bilateral stereotactic electrode implantation into one of the following brain regions: subthalamic nucleus (STN, n = 12/10), entopeduncularis nucleus (EP, n = 10/11), globus pallidus (GP, n = 10/10), medial prefrontal cortex (mPFC, n = 8/8), or dorsomedial thalamus (DM, n = 10/11).

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Jun
2013

The underlying neurobiology of addictive or repetitive behaviours, such as obsessive-compulsive disorder (OCD), involves dopaminergic dysregulation. While addictive behaviour depends strongly on mesolimbocortical dopaminergic responses, repetitive behaviours have been associated with dopaminergic dysregulation in the basal ganglia-thalamo-cortical circuitry. The present study investigates differences in brain stimulation reward in rats with quinpirole-induced compulsive checking behaviour, in order to examine if deficits in reward processing are also relevant for OCD.

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Oct
2012

Human respiratory syncytial virus (RSV) is the most important viral cause of serious pediatric respiratory illness worldwide. Currently, the most promising live-attenuated vaccine candidate is a temperature-sensitive (ts) cDNA-derived virus named rA2cp248/404/1030ΔSH, in reference to its set of attenuating mutations. In a previous clinical study, more than one-third of postvaccination nasal wash isolates exhibited partial loss of the ts phenotype.

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Jun
2012

Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects.

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Oct
2012

Multipotent mesenchymal stromal cells (MSC) secrete soluble factors that stimulate the surrounding microenvironment. Such paracrine effects might underlie the potential benefits of many stem cell therapies. We tested the hypothesis that MSC are able to enhance intrinsic cellular plasticity in the adult rat hippocampus.

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Sep
2012

The recently identified human metapneumovirus (HMPV) is a worldwide respiratory virus affecting all age groups and causing pneumonia and bronchiolitis in severe cases. Despite its clinical significance, no specific antiviral agents have been approved for treatment of HMPV infection. Unlike the case for most paramyxoviruses, the fusion proteins (F) of a number of strains, including the clinical isolate CAN97-83, can be triggered by low pH.

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Aug
2012

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming).

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May
2012

In Parkinson's disease the loss of dopamine induces motor impairment but also leads to non-motor symptoms such as cognitive impairment, anxiety and depression. Selective serotonine reuptake inhibitors (SSRI) are so far first line therapy for mood alterations in PD and have also been shown to influence cognition, however with often insufficient results due to yet not fully understood underlying pathomechanisms of the symptoms. Deficits in the generation and maturation of new neurons in the adult hippocampus seem to be key mechanisms of major depression and cognitive decline and are robustly influenced by serotonergic pharmacotherapy.

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Dec
1969

Swine are important hosts for influenza A viruses playing a crucial role in the epidemiology and interspecies transmission of these viruses. Respiratory epithelial cells are the primary target cells for influenza viruses.
To analyze the infection of porcine airway epithelial cells by influenza viruses, we established precision-cut lung slices as a culture system for differentiated respiratory epithelial cells.

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Sep
2011

Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity.
The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min.

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Aug
2011

Thyroid hormones play a critical role in brain development but also in the adult human brain by modulating metabolic activity. Hypothyroid states are associated with both functional and structural brain alterations also seen in patients with major depression. Recent animal experimental and preclinical data indicate subtle changes in myelination, microvascular density, local neurogenesis, and functional networks.

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Jun
2011

Human respiratory syncytial virus (HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV) largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC) is critical in initiating the adaptive immune response.

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Jul
2011

Death and dying are central events in the live of an organism, but neurobiological changes during this process are still rarely understood. Extracellular levels of serotonin, one of the phylogenetically oldest neurotransmitters, were measured continuously during dying. Serotonin levels increased threefold, while the EEG recorded simultaneously went down to a zero-line of no activity.

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Jul
2011

The establishment of new therapeutic indications for deep brain stimulation (DBS) is ambitiously promoted though the underlying mechanisms remain contested. Here, we report that PET-imaging and subsequent c-Fos-immunostaining in rats constitute a new translational approach to further understand DBS-mechanisms and -effectiveness.

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