1.
The Perfect Cytokine Storm: How Peripheral Immune Challenges Impact Brain Plasticity & Memory Function in Aging.
Muscat, SM, Barrientos, RM
Brain plasticity (Amsterdam, Netherlands). 2021;(1):47-60
Abstract
Precipitous declines in cognitive function can occur in older individuals following a variety of peripheral immune insults, such as surgery, infection, injury, and unhealthy diet. Aging is associated with numerous changes to the immune system that shed some light on why this abrupt cognitive deterioration may occur. Normally, peripheral-to-brain immune signaling is tightly regulated and advantageous; communication between the two systems is bi-directional, via either humoral or neural routes. Following an immune challenge, production, secretion, and translocation of cytokines into the brain is critical to the development of adaptive sickness behaviors. However, aging is normally associated with neuroinflammatory priming, notably microglial sensitization. Microglia are the brain's innate immune cells and become sensitized with advanced age, such that upon immune stimulation they will mount more exaggerated neuroimmune responses. The resultant elevation of pro-inflammatory cytokine expression, namely IL-1β, has profound effects on synaptic plasticity and, consequentially, cognition. In this review, we (1) investigate the processes which lead to aberrantly elevated inflammatory cytokine expression in the aged brain and (2) examine the impact of the pro-inflammatory cytokine IL-1β on brain plasticity mechanisms, including its effects on BDNF, AMPA and NMDA receptor-mediated long-term potentiation.
2.
Lifestyle modifications with anti-neuroinflammatory benefits in the aging population.
Muscat, SM, Barrientos, RM
Experimental gerontology. 2020;:111144
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Abstract
Aging-associated microglial priming results in the potential for an exaggerated neuroinflammatory response to a subsequent inflammatory challenge in regions of the brain known to support learning and memory. This excessive neuroinflammation in the aging brain is known to occur following a variety of peripheral insults, including infection and surgery, where it has been associated with precipitous declines in cognition and memory. As the average lifespan increases worldwide, identifying interventions to prevent and treat aging-associated excessive neuroinflammation and ensuing cognitive impairments is of critical importance. Lifestyle has emerged as a potential non-pharmacological target in this endeavor. Here, we review important and recent preclinical and clinical literature demonstrating the anti-inflammatory effects of lifestyle modifications such as exercise, diet, and environmental enrichment in the context of aging and memory. Importantly, we focus on research indicating that these lifestyle modifications do not need to be lifelong, suggesting that such interventions may be efficacious in the prevention and treatment of aging- and neuroinflammation-associated cognitive impairment, even when initiated in older age.
3.
Food for thought: how nutrition impacts cognition and emotion.
Spencer, SJ, Korosi, A, Layé, S, Shukitt-Hale, B, Barrientos, RM
NPJ science of food. 2017;:7
Abstract
More than one-third of American adults are obese and statistics are similar worldwide. Caloric intake and diet composition have large and lasting effects on cognition and emotion, especially during critical periods in development, but the neural mechanisms for these effects are not well understood. A clear understanding of the cognitive-emotional processes underpinning desires to over-consume foods can assist more effective prevention and treatments of obesity. This review addresses recent work linking dietary fat intake and omega-3 polyunsaturated fatty acid dietary imbalance with inflammation in developing, adult, and aged brains. Thus, early-life diet and exposure to stress can lead to cognitive dysfunction throughout life and there is potential for early nutritional interventions (e.g., with essential micronutrients) for preventing these deficits. Likewise, acute consumption of a high-fat diet primes the hippocampus to produce a potentiated neuroinflammatory response to a mild immune challenge, causing memory deficits. Low dietary intake of omega-3 polyunsaturated fatty acids can also contribute to depression through its effects on endocannabinoid and inflammatory pathways in specific brain regions leading to synaptic phagocytosis by microglia in the hippocampus, contributing to memory loss. However, encouragingly, consumption of fruits and vegetables high in polyphenolics can prevent and even reverse age-related cognitive deficits by lowering oxidative stress and inflammation. Understanding relationships between diet, cognition, and emotion is necessary to uncover mechanisms involved in and strategies to prevent or attenuate comorbid neurological conditions in obese individuals.