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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Migration and Phagocytic Ability of Activated Microglia During Post-natal Development is Mediated by
Aditya Sunkaria1, Supriya Bhardwaj2, Avishek Halder1
1Department of Biochemistry, Panjab University, Chandigarh, 160014, India.
Abstract:
Microglia play an important role in synaptic pruning and controlled phagocytosis of neuronal cells during developmental stages. However, the mechanisms that regulate these functions are not completely understood. The present study was designed to investigate the role of purinergic signalling in microglial migration and phagocytic activity during post-natal brain development. One-day-old BALB/c mice received lipopolysaccharide (LPS) and/or a purinergic analogue (2-methylthioladenosine-5'-diphosphate; 2MeSADP), intracerebroventrically (i.c.v.). Combined administration of LPS and 2MeSADP resulted in activation of microglia as evident from increased expression of ionised calcium-binding adapter molecule 1 (Iba1). Activated microglia showed increased expression of purinergic receptors (P2Y2, P2Y6 and P2Y12). LPS either alone or in combination with 2MeSADP induced the expression of Na(+)/Ca(2+) exchanger (NCX-1) and P/Q-type Ca(2+) channels along with MARCKS-related protein (MRP), which is an integral component of cell migration machinery. In addition, LPS and 2MeSADP administration induced the expression of microglial CD11b and DAP12 (DNAX-activation protein 12), which are known to be involved in phagocytosis of neurons during development. Interestingly, administration of thapsigargin (TG), a specific Ca(2+)-ATPase inhibitor of endoplasmic reticulum, prevented the LPS/2MeSADP-induced microglial activation and migration by down-regulating the expression of Iba1 and MRP, respectively. Moreover, TG also reduced the LPS/2MeSADP-induced expression of CD11b/DAP12. Taken together, the findings reveal for the first time that Ca(2+)-mediated purinergic receptors regulate the migration and phagocytic ability of microglia during post-natal brain development.
Insights
Purinergic signaling, mediated by calcium ions, regulates microglial migration and phagocytosis during brain development. This study reveals how these processes are controlled, offering insights into neurodevelopmental mechanisms.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia are crucial for synaptic pruning and neuronal phagocytosis during development.
- The precise mechanisms governing microglial functions remain incompletely understood.
- Purinergic signaling is implicated in various cellular processes, including immune cell activity.
Purpose of the Study:
- To investigate the role of purinergic signaling in microglial migration and phagocytosis.
- To elucidate the regulatory mechanisms of these microglial functions during post-natal brain development.
Main Methods:
- Lipopolysaccharide (LPS) and/or 2-methylthioladenosine-5'-diphosphate (2MeSADP) were administered to one-day-old mice.
- Microglial activation, receptor expression, and phagocytic markers were assessed.
- The effect of thapsigargin (TG), a Ca(2+)-ATPase inhibitor, on microglial responses was evaluated.
Main Results:
- Combined LPS and 2MeSADP administration activated microglia, increasing Iba1 expression and purinergic receptor levels (P2Y2, P2Y6, P2Y12).
- LPS and 2MeSADP induced expression of NCX-1, P/Q-type Ca(2+) channels, MRP, CD11b, and DAP12, indicating enhanced migration and phagocytosis.
- Thapsigargin treatment inhibited LPS/2MeSADP-induced microglial activation, migration, and phagocytic marker expression.
Conclusions:
- Calcium-mediated purinergic receptors play a significant role in regulating microglial migration and phagocytosis.
- These findings provide novel insights into the molecular mechanisms controlling microglial behavior during post-natal brain development.
- The study highlights the importance of purinergic signaling in neurodevelopmental processes.
