Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats

Abstract

Aging is associated with morphological, physiological and metabolic changes, leading to multiorgan degenerative pathologies, such as cognitive function decline. It has been suggested that memory loss also involves a decrease in neurotrophic factors, including brain-derived neurotrophic factor (BDNF). In recent years, microbiota has been proposed as an essential player in brain development, as it is believed to activate BDNF secretion through butyrate production. Thus, microbiota modulation by supplementation with probiotics and prebiotics may impact cognitive decline. This study aimed to evaluate the effects of probiotics and prebiotics supplementation on the memory of middle-aged rats. Sprague-Dawley male rats were randomized in four groups (n = 13 per group): control (water), probiotic (E. faecium), prebiotic (agave inulin), symbiotic (E. faecium + inulin), which were administered for 5 weeks by oral gavage. Spatial and associative memory was analyzed using the Morris Water Maze (MWM) and Pavlovian autoshaping tests, respectively. Hippocampus was obtained to analyze cytokines [interleukin (IL-1β) and tumor necrosis factor (TNF-α)], BDNF and γ-aminobutyric acid (GABA) by enzyme-linked immunosorbent assay (ELISA). Butyrate concentrations were also evaluated in feces. The symbiotic group showed a significantly better performance in MWM (p < 0.01), but not in Pavlovian autoshaping test. It also showed significantly lower concentrations of pro-inflammatory cytokines (p < 0.01) and the reduction in IL-1β correlated with a better performance of the symbiotic group in MWM (p < 0.05). Symbiotic group also showed the highest BDNF and butyrate levels (p < 0.0001). Finally, we compared the electrophysiological responses of control (n = 8) and symbiotic (n = 8) groups. Passive properties of CA1 pyramidal cells (PCs) exhibited changes in response to the symbiotic treatment. Likewise, this group showed an increase in the N-methyl-D-aspartate receptor (NMDA)/AMPA ratio and exhibited robust long-term potentiation (LTP; p < 0.01). Integrated results suggest that symbiotics could improve age-related impaired memory.

The Effects of Probiotic Lactobacillus and Bifidobacterium Strains on Memory and Learning Behavior, Long-Term Potentiation (LTP), and Some Biochemical Parameters in β-Amyloid-Induced Rat’s Model of Alzheimer’s Disease

“…Probiotic treatment presumably caused an increase in release of presynaptic neurotransmitters, resulting in an increase in LTP in the probiotic (6 weeks)+Alzheimer group. In agreement with this study, Romo-Araiza et al (2018) showed that probiotic and prebiotic supplementation was associated with an improved spatial learning and memory and significant increases in LTP in middle-aged rats. Davari et al (2013) also reported that probiotic supplementation of streptozotocin-induced diabetic rats improved impaired spatial memory and helped reverse the declines in hippocampal LTP.…”

“…Previous studies have also indicated that chronic dietary supplementation with probiotics containing Lactobacillus and Bifidobacterium improves the memory of middle-aged rats (O’Hagan et al, 2017; Romo-Araiza et al, 2018). Emerging evidence has suggested a role of the gut microbiota and probiotic supplementation in regulating cognitive function and metabolic status in AD (Leblhuber et al, 2018; Liang et al, 2015; Minter et al, 2016).…”

“…Akbari et al (2016) showed that a probiotic supplement containing Lactobacillus acidophilus , Lactobacillus casei , Bifidobacterium bifidum , and Lactobacillus fermentum improved impaired spatial learning and memory induced in AD. Romo-Araiza et al (2018) showed that consumption of probiotics ( Enterococcus faecalis ) and prebiotics (agave inulin) for 5 weeks improved synaptic plasticity in middle-aged rats. Previous studies have also shown that dietary supplements containing multiple species of live Lactobacillus and Bifidobacteria ( L. acidophilus CUL60, L. acidophilus CUL21, B. bifidum CUL20, and Bifidobacterium lactis CUL34) can affect brain functions (O’Hagan et al, 2017).…”

Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

“…180 In preterm infants, supplementation with different prebiotics showed improvement in brain development when compared to a control group. 181 Synergistic combinations of prebiotics and probiotics (synbiotics) have been found to improve age-related memory impairment in rats 182 and are now being trialled in human clinical studies to promote intestinal health. 183,184 One simple goal arising from such studies is devising optimized healthy diets which include all the required nutrients and prebiotics needed to decrease the number of harmful gut microbiota, and to increase the concentration of microorganisms producing metabolites which have beneficial effects on immunologic, metabolic and brain function to maximize health.…”

Probiotic Lactobacillus fermentum strain JDFM216 improves cognitive behavior and modulates immune response with gut microbiota

“…This result was supported by higher performances on Y-maze, accelerated rotarod, beam-walking and forced swimming tests with the administration of JDFM216. Other investigations have reported the effect of probiotics for improving memory in middle-aged rats as a therapeutic agent using the Morris water maze and Pavlovian autoshaping tests 49 . The anti-depressant effect of probiotics has been demonstrated in animal models by the FST and tail suspension test (TST) 50 , 51 .…”