Dietary Spray-Dried Porcine Plasma Prevents Cognitive Decline in Senescent Mice and Reduces Neuroinflammation and Oxidative Stress

Abstract

Aging is characterized by chronic, low-grade inflammation that correlates with cognitive decline. Dietary supplementation with spray-dried porcine plasma (SDP) reduces immune activation in rodent models of inflammation and aging. We investigated whether the anti-inflammatory properties of SDP could ameliorate age-related cognitive deterioration and preserve brain homeostasis in an aging mouse model of senescence. Male senescence-accelerated prone 8 (SAMP8) mice were used. In Experiment 1, cognitive performance (n=10-14 mice/group) was analyzed by the novel object recognition test in 2-mo-old mice (2M group) and in mice fed a control diet or a diet supplemented with 8% SDP for 2 (4M-CTL and 4M-SDP groups) and 4 mo (6M-CTL and 6M-SDP groups). In Experiment 2, the permeability of the blood-brain barrier and junctional proteins in brain tissue was assessed, as well as synaptic density, oxidative stress markers, and inflammatory genes and proteins in mice from the 2M, 6M-CTL, and 6M-SDP groups ( n=5-11). Statistical analyses included one-factor ANOVA followed by Fisher's posthoc test. 6M-SDP mice had better cognitive performance than 6M-CTL mice in both short-term (P=0.024) and long-term (P=0.017) memory tests. In brain tissue, 6M-SDP mice showed reduced brain capillary permeability (P=0.034) and increased ZO1 and E-cadherin expression (both P<0.04) compared with 6M-CTL mice. SDP also prevented the NFκB activation observed in 6M-CTL mice (P=0.002) and reduced Il6 expression and hydrogen peroxide concentration (both P<0.03) observed in 6M-CTL mice. SDP also increased the concentration of IL10 (P=0.027), an anti-inflammatory cytokine correlated with memory preservation. In senescent SAMP8 mice, dietary supplementation with SDP attenuated cognitive decline and prevented changes in brain markers of neuroinflammation and oxidative stress.