19 research outputs found
Pharmacological investigations in glia culture model of inflammation
No full textAstrocytes and microglia are the main cell population besides neurons in the central nervous system (CNS). Astrocytes support the neuronal network maintenance of transmitter and ion homeostasis. They are part of the tripartite synapse, composed of pre- and postsynaptic neurons and perisynaptic astrocytic processes as a functional unit. There is an increasing evidence that astroglia are involved in the pathophysiology of CNS disorders such as epilepsy, autoimmune CNS diseases or neuropsychiatric disorders, especially with regard to glia-mediated inflammation. In addition to astrocytes, investigations on microglial cells, the main immune cells of the CNS, offer a whole network approach leading to better understanding of non-neuronal cells and their pathological role in CNS diseases and treatment. An astrocyte-microglia co-culture model of inflammation was developed by Faustmann et al. (2003), which allows to study the endogenous inflammatory reaction and the cytokine expression under drugs in a differentiated manner. Commonly used antiepileptic drugs (e.g., levetiracetam, valproic acid, carbamazepine, phenytoin, and gabapentin), immunomodulatory drugs (e.g., dexamethasone and interferon-beta), hormones and psychotropic drugs (e.g., venlafaxine) were already investigated, contributing to better understanding mechanisms of actions of CNS drugs and their pro- or anti-inflammatory properties concerning glial cells. Furthermore, the effects of drugs on glial cell viability, proliferation and astrocytic network were demonstrated. The astrocyte-microglia co-culture model of inflammation proved to be suitable as unique model for pharmacological investigations on astrocytes and microglia with future potential (e.g., cancer drugs, antidementia drugs, and toxicologic studies)
Preincubation with antipsychotic drugs protects against in vitro phencyclidine-mediated spontaneous neuronal network suppression
No full textInhibition of Microglial Activation by Amitriptyline and Doxepin in Interferon-β Pre-Treated Astrocyte–Microglia Co-Culture Model of Inflammation
No full textDepression may occur in patients with multiple sclerosis, especially during interferon-β (IFN-β) treatment, and therapy with antidepressants may be necessary. Interactions of IFN-β with antidepressants concerning glia-mediated inflammation have not yet been studied. Primary rat co-cultures of astrocytes containing 5% (M5, consistent with “physiological” conditions) or 30% (M30, consistent with “pathological, inflammatory” conditions) of microglia were incubated with 10 ng/mL amitriptyline or doxepin for 2 h, or with 2000 U/mL IFN-β for 22 h. To investigate the effects of antidepressants on IFN-β treatment, amitriptyline or doxepin was added to IFN-β pre-treated co-cultures. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to measure the glial cell viability, immunocytochemistry was performed to evaluate the microglial activation state, and ELISA was performed to measure pro-inflammatory TNF-α and IL-6 cytokine concentrations. Incubation of inflammatory astrocyte–microglia co-cultures with amitriptyline, doxepin or IFN-β alone, or co-incubation of IFN-β pre-treated co-cultures with both antidepressants, significantly reduced the extent of inflammation, with the inhibition of microglial activation. TNF-α and IL-6 levels were not affected. Accordingly, the two antidepressants did not interfere with the anti-inflammatory effect of IFN-β on astrocytes and microglia. Furthermore, no cytotoxic effects on glial cells were observed. This is the first in vitro study offering novel perspectives in IFN-β treatment and accompanying depression regarding glia
Influence of antipsychotic drugs on microglia-mediated neuroinflammation in schizophrenia: perspectives in an astrocyte–microglia co-culture model
No full textSchizophrenia is a severe mental disorder with a strong lifetime impact on patients’ health and wellbeing. Usually, symptomatic treatment includes typical or atypical antipsychotics. Study findings show an involvement of low-grade inflammation (blood, brain parenchyma, and cerebrospinal fluid) in schizophrenia. Moreover, experimental and neuropathological evidence suggests that reactive microglia, which are the main resident immune cells of the central nervous system (CNS), have a negative impact on the differentiation and function of oligodendrocytes, glial progenitor cells, and astrocytes, which results in the disruption of neuronal networks and dysregulated synaptic transmission, contributing to the pathophysiology of schizophrenia. Here, the role of microglial cells related to neuroinflammation in schizophrenia was discussed to be essential. This review aims to summarize the evidence for the influence of antipsychotics on microglial inflammatory mechanisms in schizophrenia. Furthermore, we propose an established astrocyte–microglia co-culture model for testing regulatory mechanisms and examining the effects of antipsychotics on glia-mediated neuroinflammation. This could lead to a better understanding of how typical and atypical antipsychotics can be used to address positive and negative symptoms in schizophrenia and comorbidities like inflammatory diseases or the status of low-grade inflammation
Ammonia induced microglia activation was associated with limited effects on connexin 43 and aquaporin 4 expression in an astrocyte-microglia co-culture model
No full textBackground!#!Hepatic encephalopathy (HE) is a neurological complication resulting from acute or chronic liver disease. Hyperammonemia leading to astrocyte swelling and cerebral edema in combination with neuroinflammation including microglia activation, mainly contribute to the pathogenesis of HE. However, little is known about microglia and their inflammatory response, as well as their influence on astrocytic channels and astrocyte swelling under hyperammonemia.!##!Objective!#!To investigate the effects of ammonia on the microglial activation and morphology in different set-ups of an in vitro astrocyte-microglia co-culture model. Further, potential effects on glial viability, connexin 43 (Cx43) and aquaporin 4 (AQP4) expression were tested.!##!Methods!#!Primary rat glial co-cultures of astrocytes containing 5% (M5, representing 'physiological' conditions) or 30% (M30, representing 'pathological' conditions) of microglia were incubated with 3 mM, 5 mM, 10 mM and 20 mM ammonium chloride (NH4Cl) for 6 h and 24 h in order to mimic the conditions of HE. An MTT assay was performed to measure the viability, proliferation and cytotoxicity of cells. The microglial phenotypes were analyzed by immunocytochemistry. The expression of Cx43 and AQP4 were quantified by immunoblot analysis.!##!Results!#!A significant reduction of glial viability was observed in M30 co-cultures after incubation with 20 mM NH4Cl for 6 h, whereas in M5 co-cultures the viability remained unchanged. Microglial activation was detected by immunocytochemistry after incubation with 3 mM, 5 mM and 10 mM NH4Cl for 6 h and 24 h in M5 as well as in M30 co-cultures. The Cx43 expression was slightly increased in M30 co-cultures after 6 h incubation with 5 mM NH4Cl. Also, the AQP4 expression was slightly increased only in M5 co-cultures treated with 10 mM NH4Cl for 6 h. Under the other conditions, Cx43 and AQP4 expression was not affected by NH4Cl.!##!Conclusions!#!The novel aspect of our study was the significant microglial activation and decrease of viability after NH4Cl incubation in different set-ups of an in vitro astrocyte-microglia co-culture model, contributing to better understanding of pathophysiological mechanisms of HE. Hyperammonemia led to limited effects on Cx43 and AQP4 expression, the relevance of these minimal changes should be viewed with caution
Psychiatrische Versorgung in einer muttersprachlichen Ukraine-Ambulanz für Geflüchtete in einer psychiatrischen Universitätsklinik in Deutschland
No full textSeit Beginn des Angriffskriegs Russlands auf die Ukraine am 24. Februar 2022 sind über eine Million Menschen aus der Ukraine nach Deutschland geflüchtet. Hieraus resultiert ein sektorübergreifender Bedarf für das deutsche Gesundheitssystem, der sich im Fall von psychiatrischen Erkrankungen aus zwei verschiedenen Patientenpopulationen herleiten lässt: Einerseits besteht die Notwendigkeit zur Weiterbehandlung psychiatrisch vorerkrankter Flüchtlinge. Andererseits stellen Kriegs- und Fluchterlebnisse Belastungsfaktoren und Traumata dar, die zu Anpassungsstörungen und Traumafolgestörungen führen können oder zur Erstmanifestation anderer psychiatrischer Erkrankungen beitragen. Kriegsflüchtlinge leiden oft (in absteigender Reihenfolge) unter Depression und posttraumatischer Belastungsstörung (PTBS), Angststörung und Psychose und benötigen häufig über viele Jahre hinweg psychiatrische Hilfen. Somit besteht ein hoher Bedarf an qualifizierter psychiatrisch-psychotherapeutischer Hilfe, die ambulante Regelversorgung wird jedoch häufig durch Sprachbarrieren erschwert. Deshalb wurde seit Kriegsbeginn eine an unsere psychiatrische Institutsambulanz angeschlossene muttersprachliche Ambulanz für aus der Ukraine Geflüchtete ('Ukraine-Ambulanz') etabliert. Ziel dieser retrospektiven Auswertung der Patient*innendaten dieser Ukraine-Ambulanz ist die Charakterisierung der Patient*innenbedarfe zur Darstellung etwaiger Unterschiede und weiteren bedarfsgerechten Optimierung der medizinischen Versorgung
Psychiatrische Versorgung in einer muttersprachlichen Ukraine-Ambulanz für Geflüchtete in einer psychiatrischen Universitätsklinik in Deutschland
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