%0 Journal Article
%T Microglia and Synapse: Interactions in Health and Neurodegeneration
%A Zuzana ˋiˋkov芍
%A Marie-豕ve Tremblay
%J Neural Plasticity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/425845
%X A series of discoveries spanning for the last few years has challenged our view of microglial function, the main form of immune defense in the brain. The surveillance of neuronal circuits executed by each microglial cell overseeing its territory occurs in the form of regular, dynamic interactions. Microglial contacts with individual neuronal compartments, such as dendritic spines and axonal terminals, ensure that redundant or dysfunctional elements are recognized and eliminated from the brain. Microglia take on a new shape that is large and amoeboid when a threat to brain integrity is detected. In this defensive form, they migrate to the endangered sites, where they help to minimize the extent of the brain insult. However, in neurodegenerative diseases that are associated with misfolding and aggregation of synaptic proteins, these vital defensive functions appear to be compromised. Many microglial functions, such as phagocytosis, might be overwhelmed during exposure to the abnormal levels of misfolded proteins in their proximity. This might prevent them from attending to their normal duties, such as the stripping of degenerating synaptic terminals, before neuronal function is irreparably impaired. In these conditions microglia become chronically activated and appear to take on new, destructive roles by direct or indirect inflammatory attack. 1. Physiological Conditions Microglial cells derive from primitive myeloid progenitors (which originate from the yolk sac) invading the central nervous system (CNS) during embryonic development. As a consequence, they are the only immune cells that permanently reside in the CNS [1每3]. In the healthy CNS, microglia occupy minimally overlapping territories in which they continuously survey their environment by structurally remodeling their ramified processes on a time scale of minutes [4每8]. These surveillant microglia can respond rapidly to any pathological stimulus resulting from injury or disease by transforming their morphology and functional behavior [9每12]. Traditionally, these changes in the microglial phenotype are referred to as microglial activation. Activated microglia have the capacity to proliferate, migrate, and release reactive oxygen species, neurotoxins, and proinflammatory and anti-inflammatory cytokines. These activated microglia can secrete trophic factors, present antigens to T cells, and phagocytose pathogens, degenerating cells, and inflammatory debris [9每11, 13每15]. In addition, they can separate presynaptic terminals from the postsynaptic neuronal parts in a process known as synaptic stripping
%U http://www.hindawi.com/journals/np/2013/425845/