Related Experiment Videos
Microglia-derived plasminogen enhances neurite outgrowth from explant cultures of rat brain
K Nagata1, K Nakajima, N Takemoto
1Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan.
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.
Insights
Microglia-derived plasminogen (Pg) significantly enhances neurite outgrowth in developing rat brain neurons. This suggests Pg plays a crucial role in regulating nerve cell extension through specific binding interactions.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Microglia are known to produce and secrete plasminogen (Pg).
- The physiological role of microglial plasminogen in neuronal development remains largely unexplored.
Purpose of the Study:
- To investigate the effect of plasminogen on neurite outgrowth in the developing rat brain.
- To characterize the binding of plasminogen to neocortical neurons.
Main Methods:
- Cultured neocortical explants from embryonic rats were used to assess neurite outgrowth in serum-free medium.
- Radiolabeled 125I-Pg was employed to study plasminogen binding to dissociated neocortical neurons.
- Scatchard plot analysis was utilized to determine binding affinities.
Main Results:
- Plasminogen markedly enhanced neurite outgrowth in cultured neocortical explants.
- Plasmin, derived from plasminogen activation by urokinase (UK), also promoted outgrowth, while UK alone had no effect.
- Specific binding of plasminogen to neocortical neurons was detected, with both high- and low-affinity sites identified.
Conclusions:
- Microglia-derived plasminogen is a significant regulator of neurite extension.
- Plasminogen exerts its effects by binding to specific receptors on neocortical neurons.
- These findings highlight a novel role for microglia-derived plasminogen in neural development.