Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation.

Microglia and border-associated macrophages (BAMs) are brain-resident self-renewing cells. Here, we examined the fate of microglia, BAMs, and recruited macrophages upon neuroinflammation and through resolution. Upon infection, Trypanosoma brucei parasites invaded the brain via its border regions, triggering brain barrier disruption and monocyte infiltration.

Aged xCT-Deficient Mice Are Less Susceptible for Lactacystin-, but Not 1-Methyl-4-Phenyl-1,2,3,6- Tetrahydropyridine-, Induced Degeneration of the Nigrostriatal Pathway.

The astrocytic cystine/glutamate antiporter system x (with xCT as the specific subunit) imports cystine in exchange for glutamate and has been shown to interact with multiple pathways in the brain that are dysregulated in age-related neurological disorders, including glutamate homeostasis, redox balance, and neuroinflammation. In the current study, we investigated the effect of genetic xCT deletion on lactacystin (LAC)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of the nigrostriatal pathway, as models for Parkinson's disease (PD). Dopaminergic neurons of adult xCT knock-out mice (xCT) demonstrated an equal susceptibility to intranigral injection of the proteasome inhibitor LAC, as their wild-type (xCT) littermates.

Chronic Sulfasalazine Treatment in Mice Induces System x - Independent Adverse Effects.

Despite ample evidence for the therapeutic potential of inhibition of the cystine/glutamate antiporter system x in neurological disorders and in cancer, none of the proposed inhibitors is selective. In this context, a lot of research has been performed using the EMA- and FDA-approved drug sulfasalazine (SAS). Even though this molecule is already on the market for decades as an anti-inflammatory drug, serious side effects due to its use have been reported.

Real-life assessment of chronic rhinosinusitis patients using mobile technology: The mySinusitisCoach project by EUFOREA.

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS.

Methods: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients.

EUFOREA consensus on biologics for CRSwNP with or without asthma.

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy.

Ketamine Does Not Exert Protective Properties on Dopaminergic Neurons in the Lactacystin Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is an age-related neurodegenerative condition characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). A loss of proteasome function participates to the pathogenesis of PD, leading to the development of rodent models in which a proteasome inhibitor is applied to the nigrostriatal pathway. We recently characterized the intranigral lactacystin (LAC) mouse model, leading to nigrostriatal degeneration, motor dysfunction and alpha-synuclein accumulation.

Genetic deletion of xCT attenuates peripheral and central inflammation and mitigates LPS-induced sickness and depressive-like behavior in mice.

The communication between the immune and central nervous system (CNS) is affected in many neurological disorders. Peripheral injections of the endotoxin lipopolysaccharide (LPS) are widely used to study this communication: an LPS challenge leads to a biphasic syndrome that starts with acute sickness and is followed by persistent brain inflammation and chronic behavioral alterations such as depressive-like symptoms. In vitro, the response to LPS treatment has been shown to involve enhanced expression of system .

Slc7a11 (xCT) protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.

The cystine/glutamate antiporter (system xc-) is believed to contribute to nonvesicular glutamate release from glial cells in various brain areas. Although recent investigations implicate system xc- in mood disorders, unambiguous evidence has not yet been established. Therefore, we evaluated the possible role of system xc- in the depressive state.

Caloric Restriction Protects against Lactacystin-Induced Degeneration of Dopamine Neurons Independent of the Ghrelin Receptor.

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by a loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Caloric restriction (CR) has been shown to exert ghrelin-dependent neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-based animal model for PD. We here investigated whether CR is neuroprotective in the lactacystin (LAC) mouse model for PD, in which proteasome disruption leads to the destruction of the DA neurons of the SNc, and whether this effect is mediated via the ghrelin receptor.

Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson's disease.

In Parkinson's disease, striatal dopamine depletion leads to plastic changes at excitatory corticostriatal and thalamostriatal synapses. The functional consequences of these responses on the expression of behavioral deficits are incompletely understood. In addition, most of the information on striatal synaptic plasticity has been obtained in models with severe striatal dopamine depletion, and less is known regarding changes during early stages of striatal denervation.

In-depth behavioral characterization of the corticosterone mouse model and the critical involvement of housing conditions.

Depression and anxiety are disabling and highly prevalent psychiatric disorders. To better understand the neurobiological basis of mood and anxiety disorders, relevant animal models are needed. The corticosterone mouse model is frequently used to study depression.