Microglia‐derived plasminogen enhances neurite outgrowth from explant cultures of rat brain

Abstract

Recently, we reported the production and secretion of plasminogen (Pg) in cultured rat brain microglia [Nakajima et al., (1992) Fedn. Eur. Biochem. Socs Lett. 308, 179-182]. To investigate the physiological significance of Pg, we determined the effect of Pg on neurite outgrowth of cultured neocortical explants of an embryonic rat brain in serum-free chemically defined medium. Pg markedly enhanced the neurite outgrowth. Although plasmin, which is derived from Pg by activation by urokinase (UK), had a similar effect in this explant culture system, UK itself did not show any effect. Furthermore, we studied the characteristics of Pg binding to cultured neocortical neurons dissociated from an embryonic 16-day-old rat brain by using 125I-Pg. Specific binding of Pg to neocortical neurons was detected and Scatchard plot analysis revealed high- and low-affinity binding sites on the neurons. The estimated dissociation constants of high- and low-affinity binding sites were approximately 16.1 and 124.2 nM, respectively. These results suggest that microglia-derived Pg plays certain roles in the regulation of neurite extension through binding to the surface of neocortical neurons.

Microglia Function in Central Nervous System Development and Plasticity

“…1, bottom). Some of the first lines of evidence for this were in vitro studies in which microglia-conditioned media was added to neuronal cultures, resulting in enhanced progenitor cell proliferation and enhanced neuron survival and/or maturation (Nagata et al 1993;Chamak et al 1994;Morgan et al 2004). However, other recent work has shown that culturing NPCs isolated from cortices that lack microglia (PU.1 2/2 ) had no effect on neuron survival or neurogenesis but rather resulted in decreases in neural progenitor cell proliferation and astrogenesis, effects that were rescued by adding wild-type (WT) microglia back to the cultures (Antony et al 2011).…”

Surveillance, Intervention and Cytotoxicity: Is There a Protective Role of Microglia?

“…microglia-derived plasminogen may play a role in the regulation of neurite extension through bind ing to the surface of neocortical neurons [58]. Plasmino gen secreted from microglia could also be relevant for extracellular proteolysis, cell migration and synaptogenesis during CNS development [58], Cultured astrocytes and microglia produce and release prostaglandin E2 (PGE2) in response to stimulants such as LPS, tissue plasminogen activator (TPA), and lymphokines [59]. Since the sensitivity to these stimuli dif fers between astrocytes and microglia, PGE2 may differ entially regulate astrocyte proliferation under different physiological conditions, acting in an autocrine fashion for astrocytes and in a paracrine fashion for microglia [59].…”

“…In the developing brain, diffuse noradrenergic affcrences are present in those areas where the transient accumula tion of macrophages occurs [56,57], Another aspect of neuron-glia interrelationships is that the interaction between neurons and glia/microglia may be bidirec tional, e.g. microglia-derived plasminogen may play a role in the regulation of neurite extension through bind ing to the surface of neocortical neurons [58]. Plasmino gen secreted from microglia could also be relevant for extracellular proteolysis, cell migration and synaptogenesis during CNS development [58], Cultured astrocytes and microglia produce and release prostaglandin E2 (PGE2) in response to stimulants such as LPS, tissue plasminogen activator (TPA), and lymphokines [59].…”

Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth

“…Apod (47), Dcn (48), Dspg3 (49), Mdm2 (50), Plg (51), Sgk2 (52), and Tnfrsf18 (53)) and/or neuronal development (e.g. Apod (54), Dcn (54,55), Dspg3 (49,56), Plg (57), and Plxnb3 (58)). To identify pathways and/or biological processes impacted by Complex treatment, we used the Ingenuity Pathways Knowledge Base to assess relationships between these differentially expressed genes.…”