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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.

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VIP acts on the VPAC1 receptor to increase the trophic effect of microglia on hippocampal progenitors. A: qPCR melt curves of VPAC1 and VPAC2 from cDNA generated from either whole brain RNA or purified hippocampal microglia. For pharmacological studies, hippocampal progenitor cells were cultured for 5DIV under either 1: control conditions, 2: microglia-conditioned medium, 3: VIP (30 nM) -treated microglia-condition medium, 4: VPAC1 (30 nM) agonist-treated microglia-conditioned medium, 5: VPAC1 (1 μM) antagonist-treated microglia condition medium, 6: VIP (30 nM) and VPAC1 antagonist (1 μM) -treated microglia-conditioned medium. Cells were then fixed and stained for B: DAPI, to give total cell counts and C: nestin. *** P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).
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fig05: VIP acts on the VPAC1 receptor to increase the trophic effect of microglia on hippocampal progenitors. A: qPCR melt curves of VPAC1 and VPAC2 from cDNA generated from either whole brain RNA or purified hippocampal microglia. For pharmacological studies, hippocampal progenitor cells were cultured for 5DIV under either 1: control conditions, 2: microglia-conditioned medium, 3: VIP (30 nM) -treated microglia-condition medium, 4: VPAC1 (30 nM) agonist-treated microglia-conditioned medium, 5: VPAC1 (1 μM) antagonist-treated microglia condition medium, 6: VIP (30 nM) and VPAC1 antagonist (1 μM) -treated microglia-conditioned medium. Cells were then fixed and stained for B: DAPI, to give total cell counts and C: nestin. *** P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).

Mentions: VIP at physiological concentrations (nM) is known to act through the high affinity receptors VPAC1 and VPAC2 receptors (Harmar et al., 1998; Zaben et al., 2009). Using real-time PCR we have shown that VPAC1, but not VPAC2, receptor mRNA is expressed in postnatal hippocampal microglial cultures (Fig. 5A).


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)

VIP acts on the VPAC1 receptor to increase the trophic effect of microglia on hippocampal progenitors. A: qPCR melt curves of VPAC1 and VPAC2 from cDNA generated from either whole brain RNA or purified hippocampal microglia. For pharmacological studies, hippocampal progenitor cells were cultured for 5DIV under either 1: control conditions, 2: microglia-conditioned medium, 3: VIP (30 nM) -treated microglia-condition medium, 4: VPAC1 (30 nM) agonist-treated microglia-conditioned medium, 5: VPAC1 (1 μM) antagonist-treated microglia condition medium, 6: VIP (30 nM) and VPAC1 antagonist (1 μM) -treated microglia-conditioned medium. Cells were then fixed and stained for B: DAPI, to give total cell counts and C: nestin. *** 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

fig05: VIP acts on the VPAC1 receptor to increase the trophic effect of microglia on hippocampal progenitors. A: qPCR melt curves of VPAC1 and VPAC2 from cDNA generated from either whole brain RNA or purified hippocampal microglia. For pharmacological studies, hippocampal progenitor cells were cultured for 5DIV under either 1: control conditions, 2: microglia-conditioned medium, 3: VIP (30 nM) -treated microglia-condition medium, 4: VPAC1 (30 nM) agonist-treated microglia-conditioned medium, 5: VPAC1 (1 μM) antagonist-treated microglia condition medium, 6: VIP (30 nM) and VPAC1 antagonist (1 μM) -treated microglia-conditioned medium. Cells were then fixed and stained for B: DAPI, to give total cell counts and C: nestin. *** P < 0.001 (one-way ANOVA; Bonferroni's multiple comparison test).
Mentions: VIP at physiological concentrations (nM) is known to act through the high affinity receptors VPAC1 and VPAC2 receptors (Harmar et al., 1998; Zaben et al., 2009). Using real-time PCR we have shown that VPAC1, but not VPAC2, receptor mRNA is expressed in postnatal hippocampal microglial cultures (Fig. 5A).

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