PMID- 25575683 OWN - NLM STAT- MEDLINE DCOM- 20161114 LR - 20190831 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 53 IP - 2 DP - 2016 Mar TI - Migration and Phagocytic Ability of Activated Microglia During Post-natal Development is Mediated by Calcium-Dependent Purinergic Signalling. PG - 944-954 LID - 10.1007/s12035-014-9064-3 [doi] AB - 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. FAU - Sunkaria, Aditya AU - Sunkaria A AD - Department of Biochemistry, Panjab University, Chandigarh, 160014, India. FAU - Bhardwaj, Supriya AU - Bhardwaj S AD - Department of Dermatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. FAU - Halder, Avishek AU - Halder A AD - Department of Biochemistry, Panjab University, Chandigarh, 160014, India. FAU - Yadav, Aarti AU - Yadav A AD - Department of Biochemistry, Panjab University, Chandigarh, 160014, India. FAU - Sandhir, Rajat AU - Sandhir R AD - Department of Biochemistry, Panjab University, Chandigarh, 160014, India. sandhir@pu.ac.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150110 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CD11b Antigen) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Purinergic) RN - 0 (Tyrobp protein, mouse) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - SY7Q814VUP (Calcium) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Adenosine Diphosphate/pharmacology MH - Animals MH - Animals, Newborn MH - Brain/cytology MH - CD11b Antigen/metabolism MH - Calcium/*metabolism MH - *Cell Movement/drug effects MH - Cytoskeleton/drug effects/metabolism MH - Female MH - Intracellular Space/metabolism MH - Lipopolysaccharides MH - Male MH - Mice, Inbred BALB C MH - Microglia/*cytology/drug effects/*metabolism MH - Models, Biological MH - *Phagocytosis/drug effects MH - Receptors, Purinergic/*metabolism MH - *Signal Transduction/drug effects OTO - NOTNLM OT - Brain development OT - Calcium OT - DAP12 OT - Microglia OT - Phagocytosis OT - Purinergic receptors EDAT- 2015/01/13 06:00 MHDA- 2016/11/15 06:00 CRDT- 2015/01/11 06:00 PHST- 2014/10/01 00:00 [received] PHST- 2014/12/09 00:00 [accepted] PHST- 2015/01/11 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2016/11/15 06:00 [medline] AID - 10.1007/s12035-014-9064-3 [pii] AID - 10.1007/s12035-014-9064-3 [doi] PST - ppublish SO - Mol Neurobiol. 2016 Mar;53(2):944-954. doi: 10.1007/s12035-014-9064-3. Epub 2015 Jan 10.