Microglia play an active role in obesity-associated cognitive decline

Elise C. Cope, Elizabeth A. Lamarca, Patrick K. Monari, Lyra B. Olson, Susana Martinez, Anna D. Zych, Nicole J. Katchur, Elizabeth Gould

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Obesity 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.

Original languageEnglish (US)
Pages (from-to)8889-8904
Number of pages16
JournalJournal of Neuroscience
Volume38
Issue number41
DOIs
StatePublished - Oct 10 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Cognition
  • Dendritic spine
  • Microglia
  • Obesity
  • Synapse

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