Neurobiology

Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons.

The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and …

Extracellular vesicles from neural stem cells transfer IFN-gamma via Ifngr1 to activate Stat1 signaling in target cells.

The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural …

Neuroprotective intervention by interferon-gamma blockade prevents CD8+ T cell-mediated dendrite and synapse loss.

Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences …

Neuronal gp130 expression is crucial to prevent neuronal loss, hyperinflammation, and lethal course of murine Toxoplasma encephalitis.

The obligate intracellular parasite Toxoplasma gondii infects and persists within neurons of approximately one-third of the human population. Intracerebral control of T. gondii largely depends on interferon (IFN)-gamma-producing T cells, which induce …

Gp130-dependent astrocytic survival is critical for the control of autoimmune central nervous system inflammation.

Astrocytes are activated in experimental autoimmune encephalomyelitis (EAE) and have been suggested to either aggravate or ameliorate EAE. However, the mechanisms leading to an adverse or protective effect of astrocytes on the course of EAE are …

A key role for gp130 expressed on peripheral sensory nerves in pathological pain.

Interleukin-6 (IL-6) is a key mediator of inflammation. Inhibitors of IL-6 or of its signal transducing receptor gp130 constitute a novel class of anti-inflammatory drugs, which raise great hopes for improved treatments of painful inflammatory …

Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis.

Toxoplasma gondii infects astrocytes, neurons and microglia cells in the CNS and, after acute encephalitis, persists within neurons. Robust astrocyte activation is a hallmark of Toxoplasma encephalitis (TE); however, the in vivo function of …

gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) exerts anorectic effects by overcoming leptin resistance via activation of hypothalamic neurons. However, the exact site of CNTF action in the hypothalamus has not yet been identified. Using Cre-loxP-mediated …

Role of STAT3 and PI 3-kinase/Akt in mediating the survival actions of cytokines on sensory neurons.

The binding of cytokines to the gp130 receptor activates the STAT3, MEK/MAPK, and PI3K/Akt signalling pathways. To assess the relative importance of these pathways in promoting the survival of cytokine- dependent neurons, we conditionally inactivated …

Beta7 integrins contribute to demyelinating disease of the central nervous system.

A role for alpha4 integrins in different forms of the multiple sclerosis- like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated, but the individual contributions of alpha4beta1, alpha4beta7, and the related alphaEbeta7 …