Limits...
Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release.

Nunan R, Sivasathiaseelan H, Khan D, Zaben M, Gray W - Glia (2014)

Bottom Line: Here, we show that depleting microglia from hippocampal cultures reduces NSPC survival and proliferation.VIP, a neuropeptide released by dentate gyrus interneurons, enhances the proliferative and pro-neurogenic effect of microglia via the VPAC1 receptor.This VIP-induced enhancement is mediated by IL-4 release, which directly targets NSPCs.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Neurosciences, University of Southampton, Southampton, United Kingdom.

Show MeSH

Related in: MedlinePlus

The VIP/MG proliferative effect on hippocampal precursors is IL-4 mediated. A: VIP (30 nM) induces IL-4 gene expression in purified hippocampal microglia cells. B: Hippocampal cells express the IL-4R gene. C: Confocal images showing immunostaining of nestin cells co-expressing IL-4Ra. D and E: 5 DIV exposure to IL-4Ra antibody (10 μg/ml) inhibits the increase in nestin numbers (D) and mitotic index (E) induced by VIPtrdMGCM but not by unstimulated MGCM or direct application of VIP (30 nM) to hippocampal cultures. F: Direct application of recombinant IL-4 (10 ng/ml) for 3DIV onto microglia depleted hippocampal cultures stimulates nestin proliferation even in the absence of endogenous microglia. ***P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4336555&req=5

fig06: The VIP/MG proliferative effect on hippocampal precursors is IL-4 mediated. A: VIP (30 nM) induces IL-4 gene expression in purified hippocampal microglia cells. B: Hippocampal cells express the IL-4R gene. C: Confocal images showing immunostaining of nestin cells co-expressing IL-4Ra. D and E: 5 DIV exposure to IL-4Ra antibody (10 μg/ml) inhibits the increase in nestin numbers (D) and mitotic index (E) induced by VIPtrdMGCM but not by unstimulated MGCM or direct application of VIP (30 nM) to hippocampal cultures. F: Direct application of recombinant IL-4 (10 ng/ml) for 3DIV onto microglia depleted hippocampal cultures stimulates nestin proliferation even in the absence of endogenous microglia. ***P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).

Mentions: Microglia are known to release soluble factors that affect NSPC survival and proliferation (Cacci et al., 2008; Ekdahl et al., 2009). IL-4 is a key immune cell derived cytokine that can promote learning and memory (Derecki et al., 2010). Using quantitative PCR we found that treating microglia with 30 nM VIP resulted in a fivefold increase in mRNA expression of interleukin-4 (Fig. 6A).


Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release.

Nunan R, Sivasathiaseelan H, Khan D, Zaben M, Gray W - Glia (2014)

The VIP/MG proliferative effect on hippocampal precursors is IL-4 mediated. A: VIP (30 nM) induces IL-4 gene expression in purified hippocampal microglia cells. B: Hippocampal cells express the IL-4R gene. C: Confocal images showing immunostaining of nestin cells co-expressing IL-4Ra. D and E: 5 DIV exposure to IL-4Ra antibody (10 μg/ml) inhibits the increase in nestin numbers (D) and mitotic index (E) induced by VIPtrdMGCM but not by unstimulated MGCM or direct application of VIP (30 nM) to hippocampal cultures. F: Direct application of recombinant IL-4 (10 ng/ml) for 3DIV onto microglia depleted hippocampal cultures stimulates nestin proliferation even in the absence of endogenous microglia. ***P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4336555&req=5

fig06: The VIP/MG proliferative effect on hippocampal precursors is IL-4 mediated. A: VIP (30 nM) induces IL-4 gene expression in purified hippocampal microglia cells. B: Hippocampal cells express the IL-4R gene. C: Confocal images showing immunostaining of nestin cells co-expressing IL-4Ra. D and E: 5 DIV exposure to IL-4Ra antibody (10 μg/ml) inhibits the increase in nestin numbers (D) and mitotic index (E) induced by VIPtrdMGCM but not by unstimulated MGCM or direct application of VIP (30 nM) to hippocampal cultures. F: Direct application of recombinant IL-4 (10 ng/ml) for 3DIV onto microglia depleted hippocampal cultures stimulates nestin proliferation even in the absence of endogenous microglia. ***P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).
Mentions: Microglia are known to release soluble factors that affect NSPC survival and proliferation (Cacci et al., 2008; Ekdahl et al., 2009). IL-4 is a key immune cell derived cytokine that can promote learning and memory (Derecki et al., 2010). Using quantitative PCR we found that treating microglia with 30 nM VIP resulted in a fivefold increase in mRNA expression of interleukin-4 (Fig. 6A).

Bottom Line: Here, we show that depleting microglia from hippocampal cultures reduces NSPC survival and proliferation.VIP, a neuropeptide released by dentate gyrus interneurons, enhances the proliferative and pro-neurogenic effect of microglia via the VPAC1 receptor.This VIP-induced enhancement is mediated by IL-4 release, which directly targets NSPCs.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Neurosciences, University of Southampton, Southampton, United Kingdom.

Show MeSH
Related in: MedlinePlus