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

Abstract

Background 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. Objective 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. Methods 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. Results 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. Conclusions In senescent SAMP8 mice, dietary supplementation with SDP attenuated cognitive decline and prevented changes in brain markers of neuroinflammation and oxidative stress.

Dietary supplementation with spray-dried porcine plasma has prebiotic effects on gut microbiota in mice

“…SDP increases Parabacteroides goldsteinii, a species in the Porphyromonadaceae family that has anti-inflammatory effects in vivo, reducing Tnf-α expression in the liver 36 while inducing Il-10 expression in the proximal colon of mice 37 . The genus Blautia (Lachnospiraceae family) is positively correlated with low inflammatory status and high cognition scores 38 , and these results are compatible with the effects of SDP reported on systemic inflammation 39 and cognitive functions 40 .…”

Aging Effects on Gut Microbiota in SAMP8 Mice

“…Inflammaging can impair brain function by an increase in inflammatory cytokine expression and elevated oxidative stress, blood-brain barrier breakdown, peripheral immune cell infiltration, and glial cell activation. Our results with the SAM model support this view because we have demonstrated that this mouse model shows impaired intestinal immune response [10] as well as certain neurodegeneration that impairs memory function [11].…”

Dietary Supplementation with Spray-Dried Porcine Plasma Attenuates Colon Inflammation in a Genetic Mouse Model of Inflammatory Bowel Disease

“…These results are consistent with the acute intestinal inflammation induced by staphylococcal enterotoxin B [ 19 ], with the acute lung inflammation provoked by LPS [ 42 ], and with the uterine inflammation induced by stress [ 53 ], in which SDP supplementation increases the expression of this anti-inflammatory cytokine. In a very different condition, such as in a mouse model of senescence, SDP increases the brain concentration of IL-10, suggesting its participation in the regulation of immune responses in nonmucosal tissues [ 20 ]. All of these effects of SDP on IL-10 are remarkable because this cytokine plays an important anti-inflammatory role in restricting and suppressing the inflammatory responses, thus minimizing tissue damage in response to microbial challenges [ 54 ].…”

“…RNA isolation, reverse transcription was performed as describe previously [ 20 ]. Total RNA was retrotranscribed using an iScript cDNA Synthesis Kit (Bio-Rad, Hercules, CA, USA).…”

“…In senescent mice, SDP supplementation reduces nonspecific basal immune activation associated with age (inflammaging) by promoting mucosal regulatory T helper (Th) lymphocytes (Treg lymphocytes) and interleukin (IL)-10 production [ 18 ]. Moreover, SDP attenuates cognitive decline and reduces brain capillary permeability, oxidative stress, and proinflammatory cytokine expression in the brain of senescent mice [ 20 ].…”