Retrosplenial cortex microglia and perineuronal net densities are associated with memory impairment in aged rhesus macaques

Daniel T. Gray, Salma Khattab, Jeri Meltzer, Kelsey McDermott, Rachel Schwyhart, Irina Sinakevitch, Wolfgang Härtig, Carol A. Barnes

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Synapse loss and altered plasticity are significant contributors to memory loss in aged individuals. Microglia, the innate immune cells of the brain, play critical roles in maintaining synapse function, including through a recently identified role in regulating the brain extracellular matrix. This study sought to determine the relationship between age, microglia, and extracellular matrix structure densities in the macaque retrosplenial cortex. Twenty-nine macaques ranging in age from young adult to aged were behaviorally characterized on 3 distinct memory tasks. Microglia, parvalbumin (PV)-expressing interneurons and extracellular matrix structures, known as perineuronal nets (PNNs), were immuno- and histochemically labeled. Our results indicate that microglia densities increase in the retrosplenial cortex of aged monkeys, while the proportion of PV neurons surrounded by PNNs decreases. Aged monkeys with more microglia had fewer PNN-associated PV neurons and displayed slower learning and poorer performance on an object recognition task. Stepwise regression models using age and the total density of aggrecan, a chondroitin sulfate proteoglycan of PNNs, better predicted memory performance than did age alone. Together, these findings indicate that elevated microglial activity in aged brains negatively impacts cognition in part through mechanisms that alter PNN assembly in memory-associated brain regions.

Original languageEnglish (US)
Pages (from-to)4626-4644
Number of pages19
JournalCerebral Cortex
Volume33
Issue number8
DOIs
StatePublished - Apr 15 2023

Keywords

  • aggrecan
  • cognitive aging
  • extracellular matrix
  • innate immune system
  • synapses

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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