Effect of dietary supplementation with plasma proteins on the progression of Alzheimer's disease. Role of the microbiota and the gut-cervix in this effect.
Alzheimer’s disease (AD) is the most common type of dementia during aging and one of the most severe neurodegenerative diseases. AD is characterized by memory loss, the deposition of beta-amyloid peptides (Aβ) and the aggregation of hyperphosphorylated Tau protein (p-tau), which promote the formation of amyloid plaques and neurofibrillary cells, respectively; as well as neuroinflammation and the activation of microglia. On the other hand, during swelling, there is dysbacteriosis, and an increase in pathogenic bacteria, intestinal permeability and pro-inflammatory status is induced. Consequently, dysbacteriosis may contribute to the development of AD through different elements of the gut-cervix axis. Dietary supplementation with spray-dried porcine plasma (SDP) reduces cognitive impairment in SAMP8-wrapped mice, has anti-inflammatory effects on the intestinal mucosa in different murine models, and prebiotic effects in young animals. Given this background, the hypothesis put forward in this thesis is that the prebiotic effects of the dried plasma may be involved in its neuroprotective effects. SAMP8 mice of 2 months of age (reference group) and of 6 months of age were used, which were divided into two groups according to the experimental pulse they received during 4 months, control pulse or pulse supplemented with 8% SDP. The enveloped mice showed an improvement in cognitive function with a reduction in short- and long-term memory, in addition to a lower cortical abundance of a neurotrophin related to synaptic plasticity, such as BDNF. Supplementation with PDS prevented these effects. Senescence promoted the increase of the soluble beta fragment of the amyloid precursor protein (sAPP-β) and the generation of neurotoxic Aβ peptides. Supplementation with SDP decreased the abundance of these markers, as well as reduced the expression of β-secretase 1 (Bace1), essential in this amyloidogenic pathway. The wrapping increased the abundance of p-tau protein and protein kinases responsible for its hyperphosphorylation, which was prevented by SDP supplementation. Microglia, the immune cells specific to the central nervous system, were more activated in the cortex of senescent mice, and this process was accompanied by increased neuroinflammation. Supplementation with SDP attenuated neuroinflammation and activation of the microglia and demonstrated its anti-inflammatory effects. Thus, SDP supplementation reduces the neuropathological markers of AD. At the same time, it was demonstrated that the SAMP8 mice enveloped showed a higher degree of systemic and mucosal inflammation of the colon. This inflammatory process was accompanied by a decrease in the expression of proteins related to mucus production (Muc2, Tff3) and binding complex (Occludin). Supplementation with SDP attenuated systemic and corneal inflammation and improved barrier structure. These effects of the supplementation were associated with a reduction in the abundance of health-promoting bacteria, such as the Lactobacillus and Pediococcus genera, and an increase in others associated with inflammation, such as the Johnsonella and Erysipelothrix genera. In contrast, PDS supplementation exerted prebiotic effects, inducing the growth of probiotic bacteria and decreasing pathogenic ones. In conclusion, the anti-inflammatory effects of PDS supplementation reduce systemic inflammation in the cervical mucosa, as well as exhibiting neuroprotective properties in the enveloped mice; these effects correlate with the promotion of probiotic species, suggesting that the cervical intestinal axis may be involved in the prevention of AD.
2022
Effects of dietary supplementation with plasma proteins on immune response and cognitive impairment in an Alzheimer's disease model.
In recent years there has been an increase in life expectancy that has aroused great interest in promoting healthy aging. Usually, senescence is accompanied by different disorders and diseases at the base of which there is a dysregulation of the immune system. This dysregulation implies an increase in the basal activation of the immune system which leads to an increase in the low intensity inflammatory state, known as inflammaging. Some dietary supplements reduce the activation of the immune system, preventing cognitive impairment associated with aging through a connection between the intestine and the brain. In newly developed animals, dietary supplementation with plasma protein (PPS) improves the barrier function of the intestinal mucosa and modulates the degree of activation of the limphoid tissue associated with the intestine during an inflammatory process. In this study we have demonstrated that, at 6 months of age, mice with accelerated envelopment (SAMP8) present a non-specific activation of the intestinal immune system as well as a lower capacity of response to S. aureus enterotoxin B. Dietary supplementation with PDS for 4 months decreases the nonspecific activation of the intestinal immune system of senescent mice, since there is a lower expression of proinflammatory cytokines; moreover, the intestinal immune response of these animals against S. aureus enterotoxin B is similar to that of young mice. The 6-month-old SAMP8 mice show short- and long-term memory impairment associated with increased expression of proinflammatory cytokines, presence of oxidative agents in the brain and increased permeability of the blood-brain barrier. Senescent mice show a higher phosphorylation of Tau protein than younger mice, a fact that is related to cognitive disorders such as those observed in Alzheimer’s disease. Dietary supplementation with plasma proteins attenuates most of these effects of the wrapping on brain function, thanks to the connection between the intestinal immune system and other mucosal and systemic organs.
2017
