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Publication : Complement emerges as a masterful regulator of CNS homeostasis, neural synaptic plasticity and cognitive function.

First Author  Mastellos DC Year  2014
Journal  Exp Neurol Volume  261
Pages  469-74 PubMed ID  24975369
Mgi Jnum  J:217787 Mgi Id  MGI:5615568
Doi  10.1016/j.expneurol.2014.06.019 Citation  Mastellos DC (2014) Complement emerges as a masterful regulator of CNS homeostasis, neural synaptic plasticity and cognitive function. Exp Neurol 261:469-74
abstractText  Growing evidence points to a previously elusive role of complement-modulated pathways in CNS development, neurogenesis and synaptic plasticity. Distinct complement effectors appear to play a multifaceted role in brain homeostasis by regulating synaptic pruning in the retinogeniculate system and sculpting functional neural circuits both in the developing and adult mammalian brain. A recent study by Perez-Alcazar et al. (2014) provides novel insights into this intricate interplay between complement and the dynamically regulated brain synaptic circuitry, by reporting that mice deficient in C3 exhibit enhanced hippocampus-dependent spatial learning and cognitive performance. This behavioral pattern is associated with an impact of C3 on the functional capacity of glutamatergic synapses, supporting a crucial role for complement in excitatory synapse elimination in the hippocampus. These findings add a fresh twist to this rapidly evolving research field, suggesting that discrete complement components may differentially modulate synaptic connectivity by wiring up with diverse neural effectors in different regions of the brain. The emerging role of complement in synaptogenesis and neural network plasticity opens new conceptual avenues for considering complement interception as a potential therapeutic modality for ameliorating progressive cognitive impairment in age-related, debilitating brain diseases with a prominent inflammatory signature.
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