Polysialic acid blocks mononuclear phagocyte reactivity, inhibits complement activation, and protects from vascular damage in the retina.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly population. Its pathophysiology is linked to reactive oxygen species (ROS) and activation of the complement system. Sialic acid polymers prevent ROS production of human mononuclear phagocytes via the inhibitory sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC11) receptor.

Huperzine A Alleviates Mechanical Allodynia but Not Spontaneous Pain via Muscarinic Acetylcholine Receptors in Mice.

Chronic pain is a major health issue and most patients suffer from spontaneous pain. Previous studies suggest that Huperzine A (Hup A), an alkaloid isolated from the Chinese herb Huperzia serrata, is a potent analgesic with few side effects. However, whether it alleviates spontaneous pain is unclear.

Microglia activity modulated by T cell Ig and mucin domain protein 3 (Tim-3).

Microglia are the main innate immune cells in the central nervous system that are actively involved in maintaining brain homeostasis and diseases. T cell Ig and mucin domain protein 3 (Tim-3) plays critical roles in both the adaptive and the innate immune system and is an emerging therapeutic target for treatment of various disorders. In the brain Tim-3 is specifically expressed on microglia but its functional role is unclear.

Neurodegeneration by activation of the microglial complement-phagosome pathway.

Systemic inflammatory reactions have been postulated to exacerbate neurodegenerative diseases via microglial activation. We now demonstrate in vivo that repeated systemic challenge of mice over four consecutive days with bacterial LPS maintained an elevated microglial inflammatory phenotype and induced loss of dopaminergic neurons in the substantia nigra. The same total cumulative LPS dose given within a single application did not induce neurodegeneration.

Astrocyte-restricted disruption of connexin-43 impairs neuronal plasticity in mouse barrel cortex.

There is intensive gap-junctional coupling between glial processes, but their significance in sensory functions remains unknown. Connexin-43 (Cx43), a major component of astrocytic gap-junction channels, is abundantly expressed in astrocytes. To investigate the role of Cx43-mediated gap junctions between astrocytes in sensory functions, we generated Cx43 knockout (KO) mice with a mouse line carrying loxP sites flanking exon 2 of the Cx43 gene and the transgenic line expressing Cre recombinase under control of the glial fibrillary acidic protein promoter, which exhibited a significant loss of Cx43 in astrocytes in the barrel cortex.

Simplified protocol for isolation of multipotential NG2 cells from postnatal mouse.

Background: The functions of NG2 cells have attracted much attention since they were identified. At present, our understanding of their properties and functions is still limited due to the lack of an easy protocol for isolating them from mice.

New Method: In the present study, in postnatal mouse cortical tissue cultures, cell confluence was achieved at DIV 6-8 by frequently changing the medium in the absence of viable neurons, and abundant NG2 cells grew on top of the astrocyte layer before microglia started to thrive.

Microglial immunoreceptor tyrosine-based activation and inhibition motif signaling in neuroinflammation.

Elimination of extracellular aggregates and apoptotic neural membranes without inflammation is crucial for brain tissue homeostasis. In the mammalian central nervous system, essential molecules in this process are the Fc receptors and the DAP12-associated receptors which both trigger the microglial immunoreceptor tyrosine-based activation motif- (ITAM-) Syk-signaling cascade. Microglial triggering receptor expressed on myeloid cells-2 (TREM2), signal regulatory protein-beta1, and complement receptor-3 (CD11b/CD18) signal via the adaptor protein DAP12 and activate phagocytic activity of microglia.

Spatially pathogenic forms of tau detected in Alzheimer's disease brain tissue by fluorescence lifetime-based Förster resonance energy transfer.

In tauopathies including Alzheimer's disease (AD) tau molecules have lost their normal spatial distance to each other and appear in oligomeric or aggregated forms. Conventional immunostaining methods allow detection of abnormally phosphorylated or conformationally altered aggregated tau proteins, but fail to visualize oligomeric forms of tau. Here we show that tau molecules that lost their normal spatial localization can be detected on a subcellular level in postmortem central nervous system (CNS) tissue sections of AD patients by fluorescence lifetime-based Förster resonance energy transfer (FRET).

Alleviation of neurotoxicity by microglial human Siglec-11.

Sialic acid-binding Ig superfamily lectins (Siglecs) are members of the Ig superfamily that recognize sialic acid residues of glycoproteins. Siglec-11 is a recently identified human-specific CD33-related Siglec that binds to alpha2,8-linked polysialic acids and is expressed on microglia, the brain resident innate immune cells. Polysialylated neuronal cell adhesion molecule (PSA-NCAM) is a putative ligand of Siglec-11.

Signal regulatory protein-beta1: a microglial modulator of phagocytosis in Alzheimer's disease.

The signal regulatory protein-beta1 (SIRPbeta1) is a DAP12-associated transmembrane receptor expressed in a subset of hematopoietic cells. Recently, it was shown that peritoneal macrophages express SIRPbeta1, which positively regulated phagocytosis. Here, we found that SIRPbeta1 was up-regulated and acted as a phagocytic receptor on microglia in amyloid precursor protein J20 (APP/J20) transgenic mice and in Alzheimer's disease (AD) patients.

Immune-mediated CNS damage.

Multiple sclerosis (MS) is a demyelinating autoimmune disease. However, the persisting neurological deficits in MS patients result from acute axonal injury and chronic neurodegeneration, which are both triggered by the autoreactive immune response. Innate immunity, mainly mediated by activated microglial cells and invading macrophages, appears to contribute to chronic neurodegeneration.

Growth inhibition of mesenchymal stem cells by aspirin: involvement of the WNT/beta-catenin signal pathway.

1. Mesenchymal stem cell (MSC) therapy is drawing increasing attention in cardiology. However, the effect of aspirin, an assistant medication used extensively in the treatment of cardiovascular diseases, on MSC is not clear.