Abstract
Microglia are immune cells in the central nervous system (CNS) that contribute to primary innate immune responses. The morphology of microglia is closely associated with their functional activities. The majority of microglial studies have focused on the ramified or amoeboid morphology; however, bipolar/rod-shaped microglia have recently received much attention. Bipolar/rod-shaped microglia form trains with end-to-end alignment in injured brains and retinae, which is proposed as an important mechanism in CNS repair. We previously established a cell culture model system to enrich bipolar/rod-shaped microglia simply by growing primary microglia on scratched poly-D-lysine (PDL)/laminin-coated surfaces. Here, we investigated the role of laminin in morphological changes of microglia. Bipolar/rod-shaped microglia trains were transiently formed on scratched surfaces without PDL/laminin coating, but the microglia alignment disappeared after 3 days in culture. Amoeboid microglia digested the surrounding laminin, and the gene and protein expression of laminin-cleaving genes Adam9 and Ctss was up-regulated. Interestingly, lipopolysaccharide (LPS)-induced transformation from bipolar/rod-shaped into amoeboid microglia increased the expression of Adam9 and Ctss, and the expression of these genes in LPS-treated amoeboid-enriched cultures remained unchanged. These results indicate a strong association between laminin and morphological transformation of microglia, shedding new light on the role of bipolar/rod-shaped microglia in CNS repair.
Highlights
(i.e., 24 hours), showing peak expression 3 days after injury[23]
Our previous study showed that microglia form trains of bipolar/rod-shaped microglia alignments and become stabilized on the scratched area of a PDL/laminin-coated surface after 6 days in vitro (DIV) (Fig. 1a)[5]
The microglia alignment was unstable and disappeared after 3 DIV when these microglia became indistinguishable from the microglia in the non-scratched area, which displayed randomized morphologies with non-directional alignment (Fig. 1b)
Summary
(i.e., 24 hours), showing peak expression 3 days after injury[23]. In addition to a role in promoting axonal growth, laminin up-regulation after CNS injury has been correlated with the transformation of ramified microglia into amoeboid microglia. We showed that bipolar/rod-shaped microglia aligned only within the scratched area of the PDL/laminin-coated surface, and the alignment patterns were similar to those observed in the brain after CNS injury in vivo[9,10,16]. The microglia became amoeboid on the non-scratched area of the PDL/laminin-coated surface[5]. The lipopolysaccharide (LPS)-induced transformation of bipolar/rod-shaped microglia into an amoeboid morphology on the scratched area of a PDL/laminin-coated surface induced the up-regulation of Adam[9] and Ctss gene expression. The expression of Adam[9] and Ctss remained unchanged on non-scratched PDL/laminin-coated culture dishes that primarily contained amoeboid microglia after LPS treatment. The results of the present study indicate a close association between laminin and morphological changes in microglia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
