CCAAT/enhancer binding protein δ is a transcriptional repressor of α-synuclein.

α-Synuclein is the main component of Lewy bodies, the intracellular protein aggregates representing the histological hallmark of Parkinson's disease. Elevated α-synuclein levels and mutations in SNCA gene are associated with increased risk for Parkinson's disease. Despite this, little is known about the molecular mechanisms regulating SNCA transcription.

CD200R1 and CD200 expression are regulated by PPAR-γ in activated glial cells.

The mechanisms that control microglial activation are of interest, since neuroinflammation, which involves reactive microglia, may be an additional target in the search for therapeutic strategies to treat neurodegenerative diseases. Neuron-microglia interaction through contact-dependent or independent mechanisms is involved in the regulation of the microglial phenotype in both physiological and pathological conditions. The interaction between CD200, which is mainly present in neurons but also in astrocytes, and CD200R1, which is mainly present in microglia, is one of the mechanisms involved in keeping the microglial proinflammatory phenotype under control in physiological conditions.

CCAAT/enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E2 production in activated microglial cells.

The eicosanoid prostaglandin E2 (PGE2 ) plays important roles in neuroinflammation and it is produced by the sequential action of the enzymes cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PTGES). The expression of both enzymes and the production of PGE2 are increased in neuroinflammation. The objective of this study was to elucidate whether the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) regulates the expression of prostaglandin synthesis enzymes in neuroinflammation.

CCAAT/enhancer binding protein δ regulates glial proinflammatory gene expression.

The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ) is expressed in activated astrocytes and microglia and can regulate the expression of potentially detrimental proinflammatory genes. The objective of this study was to determine the role of C/EBPδ in glial activation. To this end, glial activation was analyzed in primary glial cultures and in the central nervous system from wild type and C/EBPδ(-/-) mice.

Modelling neuroinflammation in vitro: a tool to test the potential neuroprotective effect of anti-inflammatory agents.

Neuron-microglia co-cultures treated with pro-inflammatory agents are a useful tool to study neuroinflammation in vitro, where to test the potential neuroprotective effect of anti-inflammatory compounds. However, a great diversity of experimental conditions can be found in the literature, making difficult to select the working conditions when considering this approach for the first time. We compared the use of neuron-primary microglia and neuron-BV2 cells (a microglial cell line) co-cultures, using different neuron:microglia ratios, treatments and time post-treatment to induce glial activation and derived neurotoxicity.

Inhibition of CD200R1 expression by C/EBP β in reactive microglial cells.

Background: In physiological conditions, it is postulated that neurons control microglial reactivity through a series of inhibitory mechanisms, involving either cell contact-dependent, soluble-factor-dependent or neurotransmitter-associated pathways. In the current study, we focus on CD200R1, a microglial receptor involved in one of these cell contact-dependent mechanisms. CD200R1 activation by its ligand, CD200 (mainly expressed by neurons in the central nervous system),is postulated to inhibit the pro-inflammatory phenotype of microglial cells, while alterations in CD200-CD200R1 signalling potentiate this phenotype.

Pro-inflammatory gene expression and neurotoxic effects of activated microglia are attenuated by absence of CCAAT/enhancer binding protein β.

Background: Microglia and astrocytes respond to homeostatic disturbances with profound changes of gene expression. This response, known as glial activation or neuroinflammation, can be detrimental to the surrounding tissue. The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) is an important regulator of gene expression in inflammation but little is known about its involvement in glial activation.

DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain.

Adenosine A(2A) receptors (A(2A) Rs) are G-protein coupled receptors that stimulate adenylyl cyclase activity. The most A(2A) Rs-enriched brain region is the striatum, in which A(2A) Rs are largely restricted to GABAergic neurons of the indirect pathway. We recently described how DNA methylation controls basal A(2A) R expression levels in human cell lines.

DNA methylation regulates adenosine A(2A) receptor cell surface expression levels.

Adenosine A(2A) receptors (A(2A)Rs) appear to play important roles in inflammation and in certain diseases of the nervous system. Pharmacological modulation of A(2A)Rs is particularly useful in Parkinson's disease and has been tested in schizophrenia. However, little is known about the regulation of A(2A)R gene (ADORA2A).