that GluA2–PICK1 interactions are a key component of the effects of Aβ on synapses. “
“Although microglia is recognised as the cell-mediating innate immunity in the brain, emerging evidence suggests a role of microglia in synaptic communication and modulation. The ability of microglia to move in the neuropil and contact synapses is crucial for such a function. However, the frequency of microglial contact with synapses is not known. Microglia motility is regulated by actin polymerisation and its interaction with ionising calcium-binding adaptor protein 1 (Iba1). In order to move and make contact VX-809 nmr with synapses, delicate microglial processes should contain high levels of actin and Iba1. To study this we refined an electron microscopic postembedding immunogold method enabling us to identify and quantitatively study different
microglial constituents in intact brain tissue. ABT-888 cell line We show that Iba1 and actin were colocalised at high densities in delicate processes in the rat frontal cortex, and that these delicate processes of microglia contact synaptic elements. About 3.5% of the synapses received direct contact from microglia. There was a marked inverse correlation between the densities of Iba1/actin gold particles and the area of the microglial processes, suggesting that the most delicate processes possess the machinery to provide movement in the neuropil. The low frequency of microglia interaction with synaptic elements suggests that microglia have a limited role in overall regulation of synaptic activity. “
“Wallerian degeneration (WD) comprises a series of events
that includes activation of non-neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin-3 (Gal-3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following the sciatic nerve crush in Gal-3−/− mice. Using an in vivo model of nerve degeneration, we observed that removal of myelin debris is more efficient in Gal-3−/− than in wild-type (WT) mice; we next used an in vitro phagocytosis assay to document that the phagocytic potential of macrophages and Schwann cells was enhanced in the Gal-3−/− mice. Moreover, both RNA and protein levels for the pro-inflammatory cytokines IL-1β and TNF-α, as well as for Toll-like receptor (TLR)-2 and -4, show robust increases in injured nerves from Gal-3−/−mice compared to those from WT mice.
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