Aging-related changes in neuroimmune-endocrine function: Implications for hippocampal-dependent cognition

This article is part of a Special Issue “Neuroendocrine-Immune Axis in Health and Disease.”Healthy aged individuals are more likely to suffer profound memory impairments following a challenging life event such as a severe bacterial infection, surgery, or an intense psychological stressor, than are younger adults. Importantly, these peripheral challenges are capable of producing a neuroinflammatory response, (e.g., increased pro-inflammatory cytokines). In this review we will present the literature demonstrating that in the healthy aged brain this response is exaggerated and prolonged. Normal aging primes or sensitizes microglia and this appears to be the source of this amplified response. We will review the growing literature suggesting that a dysregulated neuroendocrine response in the aged organism is skewed toward higher brain CORT levels, and that this may play a critical role in priming microglia. Among the outcomes of an exaggerated neuroinflammatory response are impairments in synaptic plasticity, and reductions in key downstream mediators such as Arc and BDNF. We will show that each of these mechanisms is important for long-term memory formation, and is compromised by elevated pro-inflammatory cytokines.

► Healthy aged individuals are vulnerable to memory deficits following immune challenge.
► Following challenge, the healthy aged neuroinflammatory response is potentiated.
► Sensitized microglia appear to be the source of this amplified response.
► Elevated glucocorticoids may play a role in sensitizing microglia.
► Potentiated neuroinflammation in the hippocampus leads to memory impairments.