Extracellular matrix proteoglycans support aged hippocampus networks: a potential cellular-level mechanism of brain reserve

One hallmark of normative brain aging is vast heterogeneity in whether older people succumb to or resist cognitive decline. Resilience describes a brain's capacity to maintain cognition in the face of aging and disease. One factor influencing resilience is brain reserve-the status of neurobiological resources available to support neuronal circuits as dysfunction accumulates. This study uses a cohort of behaviorally characterized adult, middle-aged, and aged rats to test whether neurobiological factors that protect inhibitory neurotransmission and synapse function represent key components of brain reserve. Histochemical analysis of extracellular matrix proteoglycans, which play critical roles in stabilizing synapses and modulating inhibitory neuron excitability, was conducted alongside analyses of lipofuscin-associated autofluorescence. The findings indicate that aging results in lower proteoglycan density and more lipofuscin in CA3. Aged rats with higher proteoglycan density exhibited better performance on the Morris watermaze, whereas lipofuscin abundance was not related to spatial memory. These data suggest that the local environment around neurons may protect against synapse dysfunction or hyperexcitability and could contribute to brain reserve mechanisms.