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Microglia Play an Active Role in Obesity-Associated Cognitive Decline

Author(s): Cope, Elise C.; LaMarca, Elizabeth A.; Monari, Patrick K.; Olson, Lyra B.; Martinez, Susana; et al

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dc.contributor.authorCope, Elise C.-
dc.contributor.authorLaMarca, Elizabeth A.-
dc.contributor.authorMonari, Patrick K.-
dc.contributor.authorOlson, Lyra B.-
dc.contributor.authorMartinez, Susana-
dc.contributor.authorZych, Anna D.-
dc.contributor.authorKatchur, Nicole J.-
dc.contributor.authorGould, Elizabeth-
dc.date.accessioned2019-10-28T15:54:31Z-
dc.date.available2019-10-28T15:54:31Z-
dc.date.issued2018-10en_US
dc.identifier.citationCope, Elise C, LaMarca, Elizabeth A, Monari, Patrick K, Olson, Lyra B, Martinez, Susana, Zych, Anna D, Katchur, Nicole J, Gould, Elizabeth. (2018). Microglia Play an Active Role in Obesity-Associated Cognitive Decline.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 38 (41), 8889 - 8904. doi:10.1523/jneurosci.0789-18.2018en_US
dc.identifier.issn0270-6474-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr1q16t-
dc.description.abstractObesity affects >600 million people worldwide, a staggering number that appears to be on the rise. One of the lesser known consequences of obesity is its deleterious effects on cognition, which have been well documented across many cognitive domains and age groups. To investigate the cellular mechanisms that underlie obesity-associated cognitive decline, we used diet-induced obesity in male mice and found memory impairments along with reductions in dendritic spines, sites of excitatory synapses, increases in the activation of microglia, the brain's resident immune cells, and increases in synaptic profiles within microglia, in the hippocampus, a brain region linked to cognition. We found that partial knockdown of the receptor for fractalkine, a chemokine that can serve as a "find me" cue for microglia, prevented microglial activation and cognitive decline induced by obesity. Furthermore, we found that pharmacological inhibition of microglial activation in obese mice was associated with prevention of both dendritic spine loss and cognitive degradation. Finally, we observed that pharmacological blockade of microglial phagocytosis lessened obesity-associated cognitive decline. These findings suggest that microglia play an active role in obesity-associated cognitive decline by phagocytosis of synapses that are important for optimal function.SIGNIFICANCE STATEMENT Obesity in humans correlates with reduced cognitive function. To investigate the cellular mechanisms underlying this, we used diet-induced obesity in mice and found impaired performance on cognitive tests of hippocampal function. These deficits were accompanied by reduced numbers of dendritic spines, increased microglial activation, and increased synaptic profiles within microglia. Inhibition of microglial activation by transgenic and pharmacological methods prevented cognitive decline and dendritic spine loss in obese mice. Moreover, pharmacological inhibition of the phagocytic activity of microglia was also sufficient to prevent cognitive degradation. This work suggests that microglia may be responsible for obesity-associated cognitive decline and dendritic spine loss.en_US
dc.format.extent8889 - 8904en_US
dc.languageengen_US
dc.language.isoen_USen_US
dc.relation.ispartofThe Journal of neuroscience : the official journal of the Society for Neuroscienceen_US
dc.rightsFinal published version. This is an open access article.en_US
dc.titleMicroglia Play an Active Role in Obesity-Associated Cognitive Declineen_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1523/jneurosci.0789-18.2018-
dc.identifier.eissn1529-2401-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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