AGE-RELATED CHANGES IN GLIAL CELL PROPERTIES AND THEIR IMPACT ON EXTRACELLULAR MATRIX STRUCTURES IN THE RETROSPLENIAL CORTEX OF COGNITVELY-ASSESSED MACAQUE MONKEYS

Abstract

Impaired cognitive function is known to occur with normal brain aging and one of the most commonly reported age-related changes is a decline in memory function (Harada et al., 2013). We sought to study perineuronal nets (PNNs), an extracellular matrix structure that forms at the end of the critical period of brain development and is known to reduce brain plasticity (Sorg et al., 2016). Relatively little is known about how the properties of these structures change across the lifespan, or how potential alterations in them may impact the manifestation of age-related cognitive decline. Additionally, studies have reported that the aging brain shows increased microglial activity and pro-inflammatory status which ultimately result in the release of neurotoxic factors (Clarke et al., 2018; Conde & Streit, 2006). The implications of these microglial network changes on brain plasticity and cognition are also unclear. To address these questions, we used brain tissue from cognitively-assessed adult and aged monkeys to search for changes in PNN structure and potential correlates with age-related performance disparities on three memory-assessing tasks. We then used adjacent tissue samples from those same animals to search for any potential correlates that may exist between brain plasticity, as assessed through PNNs, and the state of microglia and astrocyte networks. We found that aged animals had fewer perineural nets in the retrosplenial cortex compared to younger animals. This decrease in perineuronal nets also correlated specifically with a lower performance on the delayed nonmatching-to-sample task. Furthermore, we found these protocols could be used to label and quantify microglia in the same region, which will allow us to continue to work towards answering our second question regarding if/how microglial changes map onto changes in the structure of perineuronal net and their potential correlates with memory decline.