Dataset Information


Interleukin-34 selectively enhances the neuroprotective effects of microglia to attenuate oligomeric amyloid-? neurotoxicity.

ABSTRACT: Microglia, macrophage-like resident immune cells in the brain, possess both neurotoxic and neuroprotective properties and have a critical role in the development of Alzheimer's disease (AD). We examined the function of Interleukin-34 (IL-34), a newly discovered cytokine, on microglia because it reportedly induces proliferation of monocytes and macrophages. We observed that the neuronal cells primarily produce IL-34 and that microglia express its receptor, colony-stimulating factor 1 receptor. IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-? (oA?), which mediates synaptic dysfunction and neuronal damage in AD. IL-34 increased the expression of insulin-degrading enzyme, aiding the clearance of oA?, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules. Consequently, microglia treated with IL-34 attenuated oA? neurotoxicity in primary neuron-microglia co-cultures. In vivo, intracerebroventricular administration of IL-34 ameliorated impairment of associative learning and reduced oA? levels through up-regulation of insulin-degrading enzyme and heme oxygenase-1 in an APP/PS1 transgenic mouse model of AD. These findings support the idea that enhancement of the neuroprotective property of microglia by IL-34 may be an effective approach against oA? neurotoxicity in AD.

PROVIDER: S-EPMC3181379 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC3877570 | BioStudies
| S-EPMC2774075 | BioStudies
| S-EPMC3447933 | BioStudies
2011-01-01 | S-EPMC3190105 | BioStudies
| S-EPMC6387160 | BioStudies
| S-EPMC3023525 | BioStudies
2014-01-01 | S-EPMC3950321 | BioStudies
| S-EPMC6674113 | BioStudies
| S-EPMC3030372 | BioStudies
| S-EPMC5072428 | BioStudies